Meritxell Pallejà Millán

importància de mantenir les seves mans netes i saludables. Aquests tallers poden ser impartits per professionals de la salut o pels mateixos docents, i solen incloure una combinació d’activitats pràctiques i teòriques per assegurar que els alumnes entenguin els beneficis de rentar-se les mans i com fer-ho correctament. L’ús d’un dispositiu amb llum ultraviolada, la tinta fluorescent i els sensors de luminescència són algunes de les maneres en què la luminescència pot ser utilitzada per visualitzar la importància de mantenir les mans netes i saludables. Aquest estudi qualitatiu forma part del projecte “l’Efectivitat d’una intervenció educativa sobre la higiene de mans en alumnat d’escoles sentinella”, en el qual s’avalua l’efectivitat de una formació i l’ús d’un dispositiu en la higiene de mans d’alumnat d’educació primària.
Objectius: Conèixer les dificultats i barreres, així com també les motivacions i l’acceptabilitat dels i les docents per integrar la intervenció sobre la higiene de mans a l’alumnat del qual són responsables per tal d’adaptar el contingut de la formació i l’activitat de rentat de mans perquè sigui eficaç al llarg del temps.
Metodologia: Estudi d’investigació qualitativa descriptiva amb un enfocament des de la fenomenologia i tècnica conversacional. L’estudi es durà a terme als dos centres educatius participants a l’estudi sobre l’Efectivitat d’una intervenció educativa sobre la higiene de mans en alumnat d’escoles sentinella durant el curs 2024-2025. La població d’estudi seran docents dels cursos que han participat en l’estudi esmenat. Es realitzaran tècniques individuals (entrevistes) i grupals (grups focals). Cada grup focal es compondrà entre 5-6 participants. Es realitzaran o no més sessions fins a la saturació de la informació. Es confeccionarà un guió temàtic i la sessió tindrà una durada de 60-90 min. Les sessions seran gravades en àudio, previ consentiment informat, i es transcriuran literalment.
IMP-226-CT V03
Anàlisis de les dades: Es realitzarà una anàlisi del contingut temàtic amb el suport de programari informàtic. Els temes, categories (i possibles subcategories) finals, s’identificaran per inducció, mitjançant l’anàlisi, reflexió profunda i debats entre les investigadores.
Resultats esperats: Els resultats esperats es plasmaran a un informe que inclogui les dificultats i barreres que perceben els i les docents participants. També es descriuran quines són les motivacions i l’acceptabilitat per poder adaptar la intervenció sobre higiene de mans.

Rationale and background: In November 2021, World Health Organization (WHO) designated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 a variant of concern and named it Omicron. The Omicron variant, and its descendant sub-lineages, such as BA.4-5, have since spread to become the dominant variant of the virus circulating worldwide. The Omicron variant has greatly increased transmissibility and immune-evasion capacity compared with prior circulating variants. In addition, there is evidence that the original mRNA vaccines provide lower protection against the Omicron variant.
Bivalent formulations (Comirnaty Original/Omicron BA.1 (bivalent BA.1) and Comirnaty Original/Omicron BA.4-5 (bivalent BA.4-5)) of Pfizer-BioNTech’s Coronavirus Disease 2019 (COVID-19) mRNA-based vaccine were authorised as booster doses in the European Union (EU) on 01 September 2022 and 12 September 2022, respectively. On 06 December 2022, the Emergency Task Force of the European Medicines Agency (EMA) concluded that “bivalent BA.4-5 may be used as a primary vaccination series in adult and children” who have not been previously vaccinated against SARS-CoV-2″.[1] Pfizer and Vaccine monitoring Collaboration for Europe (VAC4EU) are conducting this study to monitor the safety of these bivalent formulations in European countries.
Research question and objectives: Is there an increased risk of pre-specified adverse events of special interest (AESIs) after vaccination with bivalent BA.1 or bivalent BA.4-5 compared with no vaccination against COVID-19 among individuals with comparable vaccination histories?
Primary study objective To determine whether there is an increased risk of pre-specified AESIs following the administration bivalent BA.1 or bivalent BA.4-5 compared with not receiving any COVID-19 vaccine during follow-up.
Study design: A retrospective cohort design will be used to estimate the incidence of AESIs after receiving a Pfizer-BioNTech COVID-19 bivalent vaccine, and these incidences will be compared with those in a comparator group that did not receive any COVID-19 vaccine during follow-up. Exposed individuals will be matched to unexposed individuals using relevant individual characteristics listed below. For selected AESIs a self-controlled risk interval (SCRI) study design will also be used, when appropriate.
Population: The source population will comprise all individuals registered in each of the health care data sources who are eligible to receive bivalent BA.1 or bivalent BA.4-5. The study period will start on the date of availability of the bivalent BA.1, which was the first bivalent vaccine to receive authorisation in the EU (on 01 September 2022), in each participating country and will end on 31 August 2024 or the date of the latest data availability. BA.4-5 received authorisation in the EU on 12 September 2022.
Individuals will be evaluated for eligibility and time zero will be determined as the date of exposure (vaccination with bivalent BA.1 or bivalent BA.4-5. Matching will occur at time zero and follow-up will begin at time zero. Individuals who have received at least one dose of bivalent BA.1 or bivalent BA.4-5 will be included in the exposed cohort. Individuals who have not received a dose of any COVID-19 vaccine at time zero will be included in the unexposed cohort.
Variables: Exposure will be based on recorded prescription, dispensing, or administration of the bivalent BA.1 and bivalent BA.4-5 vaccines. Outcomes will be based on the AESIs proposed by the European Medicines Agency (EMA)-sponsored ACCESS project (vACcine COVID-19 monitoring readinESS) and also, for consistency, those included in the ongoing post-authorisation safety study of the Pfizer BioNTech COVID-19 monovalent vaccine (EUPAS41623). Clinical validation, using individual health records, will be carried out for specific AESIs. This manual review will be conducted by clinicians blinded to COVID-19 vaccine exposure. Confirmation of the certainty of an event diagnosis will be classified using available Brighton Collaboration case definitions and, those from other organisations, if Brighton Collaboration case definitions are not available.
Data sources: The study will be performed within the following selected data sources: Pedianet (IT), PHARMO Institute for Drug Outcomes Research (PHARMO) (NL), the Norwegian health registers (NHR) (NO), EpiChron Research Group on Chronic Diseases at the Aragon Health Sciences Institute (EpiChron) (ES), Sistema d’Informació per el Desenvolupament de la Investigació en Atenció Primària ( SIDIAP) [Information System for the Improvement of Research in Primary Care] (ES), and Clinical Practice Research Datalink (CPRD) (UK).
Study size: The sample size will be determined by the uptake of bivalent BA.1 and bivalent BA.4-5 during the study period.
Data analysis: Data from the matched cohort design will be analysed as follows:
• Conditional exchangeability: The pairs will be matched using several variables considered as potential confounders to ensure conditional exchangeability. Additional standard epidemiological methods, based on propensity scores, will be used to improve adjustment for confounding, if necessary.
• The effect estimates will be reported as risk ratios and risk differences (and their corresponding 95% CIs) for those exposed to a Pfizer-BioNTech COVID-19 bivalent vaccine compared with those not exposed to any COVID-19 vaccine during follow-up.
• Appropriate data analysis models will be used to estimate the incidence rate ratios of AESIs in the risk and the control windows in the SCRI study.

“The overarching goal of this study is to characterize the clinical course, outcomes and risk factors for myocarditis and pericarditis associated with Elasomeran vaccination. We want to investigate the natural course in terms of morbidity and to identify the relevant prognostic factors using the following study objectives:
Primary objectives:
1. To identify possible risk factors for post Elasomeran vaccine myocarditis and pericarditis including demographic characteristics, lifestyle factors, medical history, and vaccination characteristics
2. To characterize the clinical course of myocarditis and pericarditis of varying origin, including Elasomeran-associated myocarditis and pericarditis, and myocarditis or pericarditis not associated with COVID-19 vaccines, and to identify prognostic factors in the course of myocarditis and pericarditis.
Secondary objectives:
1. To identify whether there are differences in the clinical course or risk factor profile between Elasomeran-associated myocarditis and pericarditis, and myocarditis and pericarditis not associated with COVID-19 vaccines
2. If severe cases or cases with sequelae are identified, identify risk factors for severe Elasomeran-associated myocarditis and pericarditis
Study design:
The study will include two distinct designs to answer the primary and secondary objectives.
Case Cohort: To assess risk factors for development of post-vaccine myocarditis and pericarditis, a case-cohort of Elasomeran recipients will be defined in each participating database. This set will be used for the first primary objective.
VARIABLES:
Exposures: The main goal of interest is vaccination with any dose of Elasomeran.
Outcomes: Myocarditis and pericarditis cases will be confirmed based on adjudication criteria similar to the US CDC case definition; Probable and Definite cases will be included.
DATA SOURCES: This study is planned as analysis of routinely collected health data in five secondary automated electronic data sources in four countries (Denmark, Norway, Spain, and the UK).
STUDY SIZE: Considering the type of investigation, a traditional sample size calculation cannot be provided.
DATA ANALYSIS: In the Elasomeran-exposed case-cohort study, all cases of myocarditis, pericarditis and the control population will be described with respect to demographic characteristics, lifestyle factors or proxy variables of lifestyle factors (depending on the availability in each database), medical history and vaccination characteristics.”

Antecedents: El consum de tabac durant l’embaràs és la principal causa evitable de morbiditat i mortalitat tant en les embarassades com en el futur fill. Entre el 12-22% de les dones embarassades dels països industrialitzats fumen durant l’embaràs i un 13% no aconsegueixen deixar de fumar. L’embaràs es considera una oportunitat ideal per intervenir i controlar el consum de tabac entre els fumadors i les seves famílies. Tot i existeixen intervencions per donar suport durant el procés de deshabituació al tabac, les fumadores embarassades no acostumen a demanar ajuda. Les barreres que dificulten la cessació del tabac en aquesta població inclouen l’estigma social i la por a ser jutjades. Aquest estudi qualitatiu forma part del projecte “Efectivitat d’una aplicació per a dispositius mòbils a la deshabituació de tabac en dones embarassades (TOBBGEST): assaig comunitari aleatori”, en el qual d’avaluarà l’efectivitat de l’aplicació Tobbstop en dones embarassades. No obstant, és necessari el desenvolupament d’intervencions per la cessació del consum de tabac adaptades a les embarassades.
Objectius: Conèixer les dificultats o barreres que es troben o perceben les dones fumadores per deixar de fumar durant l’embaràs, així com també les motivacions, per tal d’adaptar l’aplicació TobbStop a aquesta població.
Metodologia: Estudi d’investigació qualitativa descriptiva amb un enfocament des de la fenomenologia i tècnica conversacional. L’estudi es durà a terme a l’àmbit de l’ASSIR de Reus durant el primer semestre del 2023. La població d’estudi seran dones fumadores que en els últims dos anys han estat embarassades i han intentat deixar de fumar.Es realitzaran tècniques individuals (entrevistes) i grupal (grups focals). Cada grup focal es compondrà entre 5-10 participants de diferents perfils. Es realitzaran o no més sessions fins a la saturació de la informació. Es confeccionarà un guió temàtic i la sessió tindrà una durada de 60-90 min. Les sessions seran gravades en àudio, previ consentiment informat, i es transcriuran literalment.
Anàlisis estadística: Es realitzarà una anàlisi del contingut temàtic amb el suport del programa Atlas-Ti. Els temes, categories (i possibles subcategories) finals, s’identificaran per inducció, mitjançant l’anàlisi, reflexió profunda i debats entre les investigadores.
Resultats esperats: Els resultats esperats és un informe que inclogui les dificultats i barreres que perceben les dones embarassades fumadores que volen deixar de fumar. També es descriuran quines són les motivacions i com poden ser incorporades a l’aplicació Tobbstop.

Antecedents: La mort sobtada per aturada cardiopulmonar (ACP) fora de l’àmbit hospitalari esdevé un problema major de salut pública, essent una de les primeres causes de mortalitat a Espanya. Les actuals guies de reanimació cardiopulmonar (RCP) diuen que la implementació precoç de les pautes de RCP abans de l’arribada de l’equip del Servei d’Emergències Mèdiques (SEM) augmenta la supervivència les persones amb ACP. Per aquest motiu, l’actuació de les persones que presencien un cas d’ACP esdevé un factor clau. No obstant, la població general desconeix la realització de les maniobres de RCP i l’ús del desfibril·lador extern automatitzat (DEA). Un estudi previ de l’equip va comprovar l’eficàcia dels cursos presencials sobre RCP-DEA a una mostra de població general i va detectar un gran interès social. L’ús de noves tecnologies ha permès l’extensió de la informació i de les formacions virtuals, sent una eina eficaç en aprenentatge.
Hipòtesis: La formació online en maniobres de RCP-DEA és una eina eficaç per augmentar els coneixement i les competències en RCP-DEA a la població general.
Objectiu: Avaluar l’eficàcia de la formació online en RCP-DEA realitzada per participants del Camp de Tarragona.
Metodologia: Aquest estudi es desenvoluparà en 2 fases: Fase 1) Avaluació de l’eficàcia de la formació online en els coneixements en RCP-DEA; Fase 2) Avaluació de l’eficàcia de la formació online en maniobres RCP-DEA en simulació. Es recolliran dades mitjançat un qüestionari a l’inici de la formació online i al final d’aquesta, s’avaluarà presencialment la competència en RCP-DEA mitjançant un checklist realitzat per un professional. La variable principal serà la diferència de puntuació entre el test pre- i post-formació (fase 1) i la superació o no (apte/ no apte) de la prova simulada en maniquins (fase 2).
Es realitza una anàlisis descriptiva de la diferència de puntuació pre- i post formació online i del percentatge de participants aptes i no aptes en la simulació a curt i mig termini. Les variables contínues es compararan mitjançant la prova t de Student o la prova U-Man Whitney (segons normalitat). Per a les variables categòriques, s’utilitzarà la prova de Chi quadrat de Pearson. Es farà una anàlisi multivariada per determinar quins factors influeixen de manera independent a la variable principal.
Resultats esperats: S’espera que la formació online sobre RCP-DEA sigui eficaç per millorar els seus coneixements i competències en RCP-DEA a curt i mig termini.
Aplicabilitat i Rellevància: La valoració de l’eficàcia d’aquest curs permetrà que sigui estès a diferents territoris de la comunitat, contribuint en l’expansió de coneixement de les maniobres RCP-DEA.

Els hàbits dietètics són reconeguts factors de riscs de diverses patologies respiratòries cròniques.[1]
Ambtot, l’impacte de la dieta en la preservació pulmonar no està ben establert.[2]
Amb l’objectiu de demostrar els beneficis de la dieta mediterrània (DieMet) sobre la funció
pulmonar, es va dissenyar un assaig clínic multicèntric en Atenció Primària.[3] L’equip investigador va
estar format per professionals sanitaris dels 20 CAPs que gestiona l’ICS a Tarragona, investigadors
de la Unitat de Recerca de l’IDIAPJGol i del Departament de Medicina de la URV.
Es van incloure pacients fumadors de 25-75 anys sense malaltia respiratòria coneguda, que van ser
assignats aleatòriament a grup control o intervenció (1:1). Al grup intervenció van rebre educació
nutricional para augmentat l’adherència a la DieMet mitjançant visites personalitzades, reforç
telefònic i accés a un blog d’informació dietètica. Al grup control van seguir la seva dieta habitual.
Tots els participants van rebre consell sanitari per deixar de fumar.
En una fase pilot (l’estudi DIET), es va demostrar que la intervenció proposada millorava els hàbits
dietètics, augmentant 2 punts l’adherència a la DieMet.[4] En una segona fase (l’estudi MEDIS-TAR),
es comparen els canvis entre grups respecte a la funció pulmonar (mesurada per espirometria) i
l’adherència a la DieMet (qüestionari validat de 14 ítems i determinacions bioquímiques).[5] Els
primers anàlisis mostren menor prevalença d’alteracions pulmonars dels participants amb més
adherència a la DieMet (reducció del 14,3%; p=0,004) i associació inversa entre la DieMet i la
presencia d’alteració pulmonar (OR:0,47-0,55).
Aquests resultats indican que comportaments dietètics saludables poden protegir el deteriorament
de la funció pulmonar i reforcen els beneficis de la seva promoció, conjuntament amb el
abandonament del tabac.

Rationale and background: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The Pfizer-BioNTech COVID-19 vaccine, Comirnaty® (tozinameran), a novel mRNA-based vaccine, has been authorised for use in the European Union (EU) for the prevention of COVID-19. Efficient and timely monitoring of the safety of the vaccine is needed in European countries. The safety of the Pfizer-BioNTech COVID-19 vaccine is being investigated in clinical and epidemiological studies conducted worldwide.
The Centers for Disease Control and Prevention (CDC) in the United States (US) issued a statement indicating a possible link between vaccination to prevent COVID-19 and myocarditis for both the Pfizer-BioNTech COVID-19 vaccine and the mRNA-1273 vaccine produced by Moderna. Several researchers have reported an increase in risk of myocarditis and/or pericarditis within 42 days of receiving the vaccination, compared with the risk among unexposed persons, particularly after the second dose and among young male recipients. European Medicines Agency (EMA)’s safety committee (Pharmacovigilance Risk Assessment Committee [PRAC]) has assessed recent data on the known risk of myocarditis and pericarditis following vaccination with COVID-19 vaccines Comirnaty and Spikevax (i.e., trade names for the Pfizer-BioNTech and Moderna COVID-19 vaccines, respectively). The outcome of the review confirms the risk of myocarditis and pericarditis, which is already reflected in the product information for these 2 vaccines.
To further examine the risk of myocarditis and pericarditis with the Pfizer-BioNTech COVID-19 vaccine, Pfizer and Vaccine monitoring Collaboration for Europe (VAC4EU) are conducting this study. This study is nested in the EUPAS41623 cohort study, titled Post Conditional Approval Active Surveillance Study Among Individuals in Europe Receiving the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine, which estimates the incidence rates of prespecified adverse events of special interest (AESIs) in 5 European countries among individuals who receive at least 1 dose of the Pfizer-BioNTech COVID 19 vaccine and among unvaccinated individuals.
Research question and objectives: This study will address the following research question, “”What is the clinical course of myocarditis and pericarditis cases after being vaccinated with the Pfizer-BioNTech COVID-19 vaccine in European countries?””
Primary study objective
? To describe the clinical course (treatment, survival, hospitalisations, long-term cardiac outcomes) of myocarditis or pericarditis among individuals diagnosed with myocarditis and/or pericarditis after receiving at least 1 dose of the Pfizer-BioNTech COVID-19 vaccine and among individuals diagnosed with myocarditis and/or pericarditis who had no prior COVID-19 vaccination, using a cohort study design.
Secondary study objective
? To examine and identify potential risk factors for myocarditis and pericarditis, such as age, sex, Pfizer-BioNTech COVID-19 vaccination status, vaccine doses received (e.g., first, second, third, and booster doses), and history of COVID-19, using a cohort study design
Study design: This cohort study is nested in the ongoing retrospective cohort study (EUPAS41623) titled Post Conditional Approval Active Surveillance Study Among Individuals in Europe Receiving the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine. The parent study includes individuals across 5 European countries who receive at least 1 dose of the Pfizer-BioNTech COVID 19 vaccine, as well as individuals who did not receive a COVID-19 vaccine.
For the primary objective (natural history), the study will be conducted in the cohort of cases of myocarditis and of pericarditis identified in the full population of the parent study.
In the parent study component comparing risk of AESIs in vaccinated and unvaccinated individuals, the 2 groups are matched 1:1 on date of vaccination in the vaccinated group and date of study eligibility in the unvaccinated group. Individuals are also matched on age, sex, history of COVID-19, place of residence, history of influenza vaccination, pregnancy status, immunocompromised status, presence of pre-existing medical conditions, and socioeconomic status/education level. This matched population constitutes the cohort in which risk factors for myocarditis and pericarditis will be evaluated (secondary objective). The matching variables, vaccination status, and other baseline variables to be identified in a review of the medical literature will be considered as potential risk factors for the development of myocarditis and of pericarditis.
Population: The source population will comprise all individuals across 5 European countries (i.e., the Netherlands [NL], United Kingdom [UK], Italy [IT], Norway [NO], and Spain [ES]) who are registered in the health care database(s) used in the study and who are eligible to receive the Pfizer-BioNTech COVID-19 vaccine. The study period starts on the date of conditional approval of the Pfizer-BioNTech COVID 19 vaccine in each country: 01 December 2020 in UK and 21 December 2020 in NL, IT, ES, and NO. The study period will end on 31 December 2023, however, the end date may be earlier in some data sources depending on the latest date of data availability at that time.
Variables:
Exposure to vaccines will be assessed in each data source based on recorded prescription, dispensing, or administration of the Pfizer-BioNTech COVID-19 vaccine. Vaccine administration and date of vaccination will be obtained from all possible sources that capture COVID-19 vaccination.
Myocarditis/pericarditis: Standard algorithms for myocarditis and for pericarditis will be applied to participant data sources to identify potential cases. The potential cases of myocarditis or pericarditis will be validated against information available for each data source and classified based on the definitions of the Brighton Collaboration. Cardiac symptoms for myocarditis and pericarditis are acute chest pain or pressure; dyspnoea after exercise, at rest, or lying down; fatigue; diaphoresis; and sudden death. Other non-specific symptoms in adults are palpitations, abdominal pain, dizziness, syncope and cardiogenic shock, fatigue, oedema, and cough. In infants or young children, symptoms include irritability, vomiting, poor feeding, and sweating. The detection of these signs and symptoms during the validation process will be used to determine levels of certainty of the diagnosis.
Potential risk factors for myocarditis and pericarditis are demographics (such as male sex, young ages); status of Pfizer-BioNTech COVID-19 vaccination and non-COVID vaccinations; vaccine doses received (e.g., first, second, third, and booster doses); post-vaccination risk window of 1 14 days; history of COVID-19 and other infectious diseases; status of immunocompromising conditions and systemic immune-mediated diseases; and comedication use (prescriptions or dispensings only) during the year before time zero (defined as date of vaccination, or matched index date for comparator).
Treatments for myocarditis based on clinical presentation of mild symptoms include paracetamol and antivirals for viral myocarditis; immunosuppression treatment for autoimmune myocarditis; heart failure therapy (i.e., beta-blockers, diuretics, angiotensin-converting enzyme [ACE] inhibitors or angiotensin-II receptor blockers [ARBs], aldosterone agonists, cardiac glycosides or calcium-channel blockers); and procedures (i.e., pacemaker, implantable cardiac defibrillator, mechanical circulatory support, and heart transplantation).
Treatments for pericarditis include antimicrobial treatment (for pericarditis of proven infectious origin); anti-inflammatory treatment (non-steroidal anti-inflammatory drugs [NSAIDs] and colchicine [for recurrent pericarditis]); and procedures (i.e., intrapericardial administration of steroids; pericardioscopy for direct instillation of treatments into the pericardial space; pericardial drainage; subdiaphragmatic laparoscopic technique, video-assisted thoracoscopic technique, and pericardioscopy for easy drainage of effusion; pericardiocentesis; cardiac catheterisation during pericardiocentesis; balloon pericardial window formation; instillation of sclerosing agents or fibrinolytic agents; and pericardiectomy).
Potential outcomes for myocarditis that will be evaluated are recovery, survival, hospitalisations, sudden cardiac death, heart failure, cardiogenic shock, fulminant myocarditis, inflammatory cardiomyopathy, heart transplant, and arrhythmia.
Potential outcomes for pericarditis that will be evaluated are recovery, survival, hospitalisations, and chronic, restrictive, and recurrent pericarditis.
Data sources: The study will be performed using the following data sources: PHARMO (PHARMO Institute for Drug Outcomes Research) (NL), ARS Toscana (Agenzia Regionale di Sanità della Toscana) (IT), Pedianet/Health Search Database (HSD) (IT), EpiChron (EpiChron Research Group on Chronic Diseases) (ES), CPRD (Clinical Practice Research Datalink) (UK), the Norwegian health registers (NO), and SIDIAP (Sistema d’Informació per el Desenvolupament de la Investigació en Atenció Primària) [Information System for the Improvement of Research in Primary Care] (ES).
Study size: The study will be conducted in a source population of 38.9 million individuals captured across the electronic healthcare data sources. The 42-day risk of myocarditis has been reported to be 2.13 cases per 100,000 vaccinated individuals and about one-third of this in unvaccinated individuals. Therefore, we expect to identify approximately 469 cases of myocarditis among vaccinated individuals and 150 cases among unvaccinated individuals.
Data analysis:
Natural history of myocarditis and pericarditis (primary objective): Individuals will be followed through recovery, death, or end of study period, whichever occurs first. The distributions of vaccination status and other baseline characteristics will be described. For continuous variables, means, standard deviations and quartiles will be estimated. For categorical variables, counts and proportions will be estimated. The missingness of variables will also be described. The occurrence of the different treatments and outcomes during follow-up will be described using counts and proportions. Continuous variables (e.g., length of stay) will be described using means, standard deviations and quartiles. When appropriate, the occurrence of time-to-event outcomes (e.g., death) will be described using the Kaplan-Meier estimator or curve.
Analysis will be performed overall by sex and age, COVID-19 history, vaccination status, and time since vaccination.
Risk factors for myocarditis and pericarditis (secondary objective): All individuals in the matched cohort of the parent study will be followed from the date of matching (i.e., the date of vaccination for those in the vaccinated group and a matched calendar date in the unvaccinated group) until the earliest occurrence of the following:
? Diagnosis of myocarditis or pericarditis
? Death
? Administrative end of follow-up
? Receipt of a non-Pfizer-BioNTech COVID-19 vaccine
? Unvaccinated member of the pair is vaccinated with the Pfizer-BioNTech COVID-19 (both the unvaccinated and vaccinated individuals of the pair will be censored).
All baseline variables, including vaccination status, will be treated as potential risk factors or effect modifiers for the development of myocarditis and/or pericarditis. A regression-based predictive analysis will be conducted to identify the variables that better predict the diagnoses. The strength of the association between the risk factors and a diagnosis of myocarditis or pericarditis will be estimated via odds ratios or hazard ratios, as appropriate.

Implementation of the study ind IDIAP Jordi Gol include three stages:
*Stage One: Identification of cases
-We will use the Myocarditis and Pericarditis case identification data dictionary to identify cases using the ICD10CM codes provided.
-We will also collect demographic and the exposure variable (COVID-19 Vaccine) guided by the data dictionary.
*Stage Two: Case confirmation via chart review/review of clinical records
-Once we finish stage one, we will collect the information and fill the Myocarditis and Pericarditis case confirmation form in REDCap platform for the second stage which includes:
– Confirmation of cases via chart review/review of clinical records using Brighton Collaboration standards, in our case we will you use free text (MEAP).
-Additional data collection for association and descriptive analysis.
*Stage Three: Data analysis and submission of results o after data collection is complete, IDIAPJGol will send aggregate results trought DRE platform.
– R-scripts will be sent to IDIAP JGol research group to run and create the results.
– Results will be uploaded to DRE platform.
-All data will be and stored at local level.

Implementation of the study ind IDIAP Jordi Gol include three stages:
*Stage One: Identification of cases
-We will use the VITT case identification data dictionary to identify cases using the ICD10CM codes provided.
-We will also collect demographic and the exposure variable (COVID-19 Vaccine) guided by the data dictionary.
*Stage Two: Case confirmation via chart review/review of clinical records
-Once we finish stage one, we will collect the information and fill the VITT case confirmation form in REDCap platform for the second stage which includes:
– Confirmation of cases via chart review/review of clinical records using Brighton Collaboration standards, in our case we will you use free text (MEAP).
-Additional data collection for association and descriptive analysis.
*Stage Three: Data analysis and submission of results o after data collection is complete, IDIAPJGol will send aggregate results trought DRE platform.
– R-scripts will be sent to IDIAP JGol research group to run and create the results.
– Results will be uploaded to DRE platform.
-All data will be and stored at local level.

Implementation of the study ind IDIAP Jordi Gol include three stages:
*Stage One: Identification of cases
-We will use the GBS case identification data dictionary to identify cases using the ICD10CM codes provided.
-We will also collect demographic and the exposure variable (COVID-19 Vaccine) guided by the data dictionary.
*Stage Two: Case confirmation via chart review/review of clinical records
-Once we finish stage one, we will collect the information and fill the GBS case confirmation form in REDCap platform for the second stage which includes:
– Confirmation of cases via chart review/review of clinical records using Brighton Collaboration standards, in our case we will you use free text (MEAP).
-Additional data collection for association and descriptive analysis.
*Stage Three: Data analysis and submission of results o after data collection is complete, IDIAPJGol will send aggregate results trought DRE platform.
– R-scripts will be sent to IDIAP JGol research group to run and create the results.
– Results will be uploaded to DRE platform.
-All data will be and stored at local level.

RATIONALE AND BACKGGROUND: The novel coronavirus SARS-CoV-2, the cause of COVID-19, has resulted in a global pandemic. The Pfizer-BioNTech COVID-19 vaccine, tozinameran (Comirnaty®) a novel mRNA-based vaccine, has been authorised for use in the European Union (EU), for the prevention of COVID-19. Efficient and timely monitoring of the safety of the vaccine is needed in European countries.
RESEARCH QUESTION AND OBJECTIVES:
Is there an increased risk of select adverse events of special interest (AESI) after being vaccinated with the Pfizer-BioNTech COVID-19 vaccine?
OBJECTIVES
Primary study objective
To determine whether an increased risk of prespecified AESI exists following the administration of at least one dose the Pfizer-BioNTech COVID 19 vaccine using two approaches: (a) a cohort design comparing risk in vaccinated and non-vaccinated individuals and (b) a self-controlled risk interval (SCRI) design.
Secondary study objectives
— To estimate the incidence rates of prespecified AESI among individuals who receive at least one dose of the Pfizer-BioNTech COVID 19 vaccine using a cohort study design.
— To describe the incidence rates and determine whether an increased risk of prespecified AESI exists following the administration of at least one dose the Pfizer-BioNTech COVID 19 vaccine compared with a matched comparator group with no COVID 19 vaccination within subcohorts of interest (i.e., individuals who are immunocompromised, individuals who are frail and have comorbidities, individuals diagnosed with previous COVID 19 infection, and age-specific groups) in Europe using a cohort study design and/or a SCRI design.
— To determine whether an increased risk of prespecified AESI exists following the administration of at least one dose of the Pfizer-BioNTech COVID 19 vaccine compared with no COVID-19 vaccination, in pregnant people and their neonates using a cohort study design.
— To characterise utilisation patterns of Pfizer-BioNTech COVID 19 vaccine among individuals within Europe, including estimating the proportion of individuals receiving the vaccine; two-dose vaccine completion rate and distribution of time gaps between the first and second doses; and demographics and clinical characteristics of recipients, overall and among subcohorts of interest, such as individuals who are immunocompromised, elderly, or have specific comorbidities.
STUDY DESIGN: A retrospective cohort design will be used to estimate the incidence of AESI after receiving vaccine doses and compare this incidence with that occurring in an unvaccinated comparator group matched on relevant individual characteristics (e.g., age, comorbidities). Where appropriate, the study will also use a SCRI design.
Population: The source population will comprise all individuals registered in each of the health care data sources who are eligible to receive the Pfizer-BioNTech COVID-19 vaccine. The study period will start on the date of launch of the Pfizer-BioNTech COVID-19 vaccine and will end on the date of the latest data availability or 31 Dec 2023. It is expected that follow-up will last for 2 years for AESI. People who are pregnant at time of vaccination or who become pregnant within two years of study start and their live born infants will be followed for an additional 12 months to collect information about birth outcomes and linked infant outcomes.
VARIABLES: Exposure will be based on recorded prescription, dispensing, or administration of the Pfizer-BioNTech COVID-19 vaccine. Vaccine administration and date of vaccination should be obtained from all possible sources that capture COVID-19 vaccination. The outcomes will be based on the AESI proposed by the European Medicines Agency (EMA) sponsored ACCESS project (vACcine COVID-19 monitoring readinESS). AESI will be identified based on patient profile review of electronic records by health care professionals. In addition, manual review of patient charts conducted by clinicians blinded to COVID-19 vaccine exposure will be performed. Confirmation of an event diagnosis will be classified against existing definitions of the Brighton Collaboration and those currently being developed. Key covariates include demographics; COVID-19 history, as available in each data source (will be used to define a subgroup of interest); personal lifestyle characteristics; comorbidities; immunocompromising conditions (will be used to define subgroups for secondary analyses); comedication use during the year before time zero (prescriptions or dispensing, no over-the-counter medication use); health care utilisation descriptors; other vaccinations; and surrogates of frailty.
Data sources: The study will be performed within the following selected data sources: PHARMO (PHARMO Institute for Drug Outcomes Research) (NL), ARS Toscana (Agenzia Regionale di Sanita’ della Toscana) (IT), Pedianet/Health Search Database (HSD) (IT), EpiChron (EpiChron Research Group on Chronic Diseases at the Aragon Health Sciences Institute) (ES), CPRD (Clinical Practice Research Datalink) (UK), the Norwegian health registers (NO), and SIDIAP (Sistema d’Informació per el Desenvolupament de la Investigació en Atenció Primària) [Information System for the Improvement of Research in Primary Care] (ES).
DATA ANALYSIS: The distributions of baseline characteristics at time zero by exposure group will be calculated to describe the study cohort and illustrate differences between the groups. For safety outcomes, the risk over specific time period(s), incidence rates and their corresponding 95% confidence intervals (CIs) will be computed after the receipt of a first dose and similarly after the receipt of a second dose. Crude risks, cumulative incidence over different time periods, and measures of association (risk differences and risk ratios) for each AESI after vaccination will be estimated in the entire population overall across both doses and separately by dose. Subgroup analyses will be conducted by subgroups defined by demographic and clinical characteristics as well as other covariates of interest. Individuals following each vaccination category under study (vaccination with at least one dose of the Pfizer-BioNTech vaccine vs. no vaccination) may have different characteristics that may determine their risk of AESI. To account for such potential confounding, propensity score methods will be used to estimate the adjusted risk ratios and 95% CIs. Using the main estimates from each data source, appropriate random-effects meta-analytic methods will be used to obtain a combined effect estimate. Where appropriate, the study will also use a SCRI design.

Rationale and background:
The global rapid spread of COVID-19 caused by the SARS-CoV2 triggered the need for developing vaccines to control for this pandemic. This study will create readiness and allows for rapid assessment of the association of adverse events of special interest (AESI) following COVID-19 vaccination.

Research question and objectives:
Readiness
The readiness phase will include the following objectives:
?To provide an overview of the methods for identification of COVID-19 vaccine exposure in the datasources
?To monitor the number of individuals exposed to any COVID-19 vaccine and to compare this to COVID-19 vaccine exposure (benchmark: https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-tracker.html#uptake-tab)
?To quantitatively evaluate different algorithms to identify adverse events by provenance in electronic health care data
?To conduct time-to-onset analyses for the AESI with respect to time since vaccination
?To assess the association between negative control events and the vaccines of interest using the SCRI to estimate systematic bias
?To test the impact of different comparators in the cohort design, using the negative control design
?To generate information for testing of methodological questions around misclassification of events/exposure

Rapid assessment studies
Primary objective
The primary objective for this rapid assessment study is to assess the potential association between the occurrence of specific AESIs and vaccination with COVID-19 vaccines within disease-specific risk periods in individuals exposed to the COVID-19 vaccines compared to other COVID-19 vaccine exposed individuals, or compared to a control window within the same individual.

Secondary objectives
The secondary objectives for the rapid assessments studies are:
?To assess the potential association between the occurrence of specific AESIs and vaccination with COVID-19 vaccines in the following subgroups
*immunocompromised persons
opersons with presence of co-morbidities elevating the risk of serious COVID-19
opersons with a history of diagnosed COVID-19 disease
opregnant women
oage groups (<18 , 18-64, 65 years and more) opatients with a prior history (ever) of that event more than a year before. Study design: A retrospective, multi-database, self-controlled risk interval or cohort study, conducted during the study period ranging from December 1, 2020 to latest availability of data. The self-controlled study will compare against non-vaccinated, and the cohort analysis against another COVID-19 vaccine. As part of the methods development work in the CVM project we will explore implementation of the use of an active comparator in the SCRI allowing comparison with the estimates from the cohort analysis , and different comparators for the cohort design. This will first be tested using the negative control events in the readiness phase and results may inform sensitivity analyses for the rapid evaluation studies. For death, the SCRI design will be adapted, and start at date of vaccination, with comparison of in different intervals of the postvaccination window. For events with high fatality rate a sensitivity analyses will be conducted with those that survive both the control and vaccination risk window Population: All subjects in the source population in the participating data sources who were in follow-up for at least 365 days on December 1, 2020 or were born into the cohort during the study period, and for whom vaccination data would be able to be obtained/linked. Variables: Variables of interest will be: ?Person-time: birth and death dates as well as periods of observation. ?Events: dates of medical and/or procedure and/or prescription/dispensing codes to identify AESI, COVID-19 and at-risk medical conditions. ?Vaccines: vaccine brands Data sources: The study will include data from 9 electronic health care data sources in 5 European countries (Italy, Netherlands, Spain, Norway, United Kingdom) that can link event data to vaccination data. Data sources will capture outcomes from hospitalization and/or general practice Study size: The source population will comprise approximately 40 million individuals Data analysis: In the readiness phase we will use negative control outcomes to assess the impact of misclassification of outcome and exposure, confounding and choice of comparators. Relative risks of specific AESI will be estimated for each specific brand of COVID-19 vaccine in comparison to non-vaccinated individuals (prior to vaccination or in non-vaccinated) and between different Covid-19 vaccines. For secondary analysis stratified analyses will be conducted.

RATIONALES AND BACKGROUND
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causes coronavirus disease 2019 (COVID-19) and has led to a global pandemic. A mass vaccination campaign is currently underway in Europe. The mRNA-1273 vaccine, currently known as Spikevax,1 combines Moderna’s mRNA (messenger ribonucleic acid) delivery platform with the stabilised SARS-CoV-2 spike immunogen.

RESEARCH QUESTION AND OBJECTIVES
The overarching research question of this study: Is the occurrence of each adverse event of special interest (AESI) among persons vaccinated with Spikevax in Europe higher than the occurrence of that AESI that would have been expected in the same population in the absence of Spikevax?
Primary objective:
? To assess whether vaccination with Spikevax (by dose number where feasible and for any dose) is associated with increased rates of the AESI compared with the expected rates overall and stratified by country, sex, and age group.
Secondary objective:
? To assess whether vaccination with Spikevax is associated with increased rates of the AESI compared with the expected rates in subpopulations of interest: women of childbearing age, patients who are immunocompromised, patients previously diagnosed with COVID-19 infection, patients with unstable health conditions and morbidities, and patients with autoimmune or inflammatory disorders

STUDY DESIGN
This study will proceed in two phases: signal detection and signal evaluation.
For the signal detection stage, population-based, country-specific historical general population background rates of the AESI estimated in the participating databases/countries from 2017-2019 will be used as estimates of the expected rates in the unvaccinated. Rates in Spikevax recipients will be compared with the historical pre-pandemic rates. All comparisons will be conducted stratified by country, and within each country further stratified on sex, and age groups.
For the signal evaluation stage, conducted as needed based on findings from signal detection, analytic approaches will be selected based on the best methodologic fit for a given AESI. It is anticipated that a combination of self-controlled designs and cohort designs using either historical or concurrent unexposed comparators will be utilised.

POPULATION
Recipients of Spikevax will be identified between 6 January 2021 (date of the earliest approval of Spikevax in Europe) and 31 December 2022 and members of the database source population selected for each study design, including persons providing historical rates from 2017-2019, will be eligible for inclusion in the study and will constitute the overall cohort. Subgroups of interest will include adolescents, adults, elderly individuals, patients who are immunocompromised, patients previously diagnosed with COVID-19 infection, patients with unstable health conditions and morbidities, and patients with autoimmune or inflammatory disorders (defined below). Individuals receiving more than one type of COVID-19 vaccine will be excluded.

VARIABLES
Cohort members will be described with respect to available demographic characteristics, medical history, medication use, and receipt of other vaccines.
Outcomes of interest will include AESI primarily based on the list defined by the Safety Platform for Emergency vACcines (SPEAC) and endorsed for COVID-19 vaccine safety assessment by the WHO Global Advisory Committee for Vaccine Safety, by the EMA and by the US CDC. Other AESI may be considered if relevant signals appear during the study conduct or additional outcomes are added to the ACCESS protocol.

DATA SOURCES
This study is planned as analysis of routinely collected health data in secondary automated electronic data sources in Denmark, Italy, Norway, Spain, and the UK, selected based on availability of the required routinely collected data, including information on vaccine brand and frequency of data updates.

STUDY SIZE
As of 1 June 2021, it is estimated that the participating databases together will be able to identify at least 431,216 recipients of Spikevax.
For signal detection, incidence rates among Spikevax vaccinees will be computed and compared using relative or absolute measures of association against appropriate (e.g., age- sex- country-specific) general population background AESI rates.
For signal evaluation using self-controlled designs, the ratio between the incidence rate estimate in the risk period and the incidence rate estimate in the control period (incidence rate ratio) will be computed using conditional Poisson regression. For parallel cohort designs, appropriate contrasts will be estimated in exposed vs. unexposed cohorts, while controlling for measured confounding. Whenever appropriate incidence rate ratios (IRRs) will be estimated with appropriate 95% confidence intervals (CIs).

MILESTONES
Data collection will continue through 31 March 2023 with a final study report planned by December 2023.

RATIONALE AND BACKGROUND: Intensive monitoring of adverse reactions following immunization (AEFI) with COVID19 vaccines or cohort event monitoring has been performed on (sub)national levels. However, the exact data collection and analysis methods, study populations, and vaccines monitored varied. For the already marketed and upcoming COVID-19 vaccines, a pan-European cohort monitoring system is an important addition to existing spontaneous reporting systems for signal detection. This is of particular importance in fragile populations (e.g. immunocompromised) who may be at higher risk of developing vaccine-related adverse reactions as well as in those patients’ categories that have not been included in COVID-19 vaccine premarketing clinical studies (e.g. pregnant and lactating women, children and adolescents). This will enable the collection of patient-reported safety data to generate incidence rates of vaccine-related adverse reactions in those special cohorts.
OBJECTIVES
* Primary aim
– To generate and compare incidence rates of patient-reported adverse reactions of different COVID-19 vaccines across the participating countries in pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy and people with prior SARS-CoV-2 infection
* Secondary aim
– Within each special cohort of vaccinees to identify potential predictors of the most frequently reported adverse reactions related to different COVID-19 vaccines.
STUDY DESIGN: Prospective cohort study in special populations (pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy and people with prior SARS-CoV-2 infection). In different countries, on the national level, data will be prospectively collected, directly from a cohort of vaccine recipients. The common core data from different countries will be pooled, stratified by special cohort and analysed at the European level. The study is set up as a cohort monitoring for a duration of up until 6 months from the first dose vaccination date (except for pregnant women who will be followed up until 1.5 month after the pregnancy end).
* Vaccine recipients should be asked to fill in questionnaires at baseline, and 1 and 3 weeks after the first dose (and eventually the second dose), and 3 and 6 months after first dose vaccination. The exact timing of the sending of the third questionnaire will depend on the vaccination interval between two doses. As regards pregnant women a specific “”End of Pregnancy”” questionnaire will be additionally sent within 1.5 months from the estimated delivery to collect information on outcomes related to pregnancy and new-born.
STUDY POPULATION: Pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy and people with prior SARS-CoV-2 infection who received COVID-19 vaccines first dose within 48 hours, consenting to participate and with a baseline questionnaire as well as questionnaires filled out after vaccination at multiple time points. Participants will be recruited before or at the moment of vaccination (as mentioned earlier within 48 hours from first dose vaccination at latest), which may differ per country and target group. There is the possibility of recruiting participants receiving a COVID-19 vaccine booster in the future, namely those who have already received a complete cycle of vaccination.
? Variables: Vaccine brand and batch number, ADRs, age, sex, height and weight, geographical area, medical history including information on comorbidities and concomitant diseases (e.g. diseases or drugs affecting the immune system, history of allergy and SARS-CoV-2 prior infection, etc.). In addition, for pregnant women: baseline variables for pregnancy (e.g., gestity, parity, previous pregnancy complications, ongoing pregnancy due date, etc.) and outcomes of pregnancy and new-born (pregnancy complications, end of pregnancy week, delivery mode, pregnancy outcomes and neonatal outcomes).
? ADRs: Suspected short- and medium/long-term adverse reactions that are reported after each dose of COVID-19 vaccination (as both solicited and unsolicited events) by the participant. All serious adverse reactions will be assessed by a qualified assessor, taking into account all information including possible uploads of documents by participants or comments on these events. When consent has been given by a participant, follow-up will be requested by e-mail for verification and upgrading of the clinical documentation grade. Otherwise, serious ADR assessment will be carried out by regional center of pharmacovigilance or local pharmacovigilance responsible person, in agreement with national pharmacovigilance legislation. Outcomes of pregnancy and new-born will also be explored in pregnant women.
DATA SOURCES: Safety data can be directly reported by vaccine recipients in their local language using the Lareb Intensive Monitoring (LIM) web app or the ResearchOnline web app, which have been both built specifically for patient-reported outcomes using exactly the same structure. As regards pregnancy monitoring, only ResearchOnline will be used as collecting additionally information on pregnancy. Collected data from European countries using LIM/ResearchOnline web app can be stored in dedicated central databases.
STUDY SIZE: We aim to include overall up to 60,000 vaccine recipients belonging to the special cohorts from 9 European countries, with a maximum of up to 30,000 pregnant and lactating women, up to 10,000 children, up to 20,000 immunocompromised, up to 10,000 persons with history of SARS-CoV-2 infection, and up to 5,000 with a history of allergies.
DATA ANALYSIS: For each special cohort, adverse reaction incidence rates will be reported overall and stratified and compared across different vaccine brands, gender, age groups, and countries.

RATIONALE AND BACKGROUND
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causes coronavirus disease 2019 (COVID-19) and has led to a global pandemic. A mass vaccination campaign is currently underway in Europe. The mRNA-1273 vaccine, currently known as Spikevax,1 combines Moderna’s mRNA (messenger ribonucleic acid) delivery platform with the stabilized SARS-CoV-2 spike immunogen, developed by NIAID.

RESEARCH QUESTION AND OBJECTIVES
The overarching research question is: is there a greater risk or prevalence of pregnancy complications, adverse pregnancy outcomes, or adverse neonatal outcomes following pregnancies exposed to Spikevax compared with pregnancies unexposed to Spikevax?
Primary objectives:
? To determine whether exposure to the Spikevax during pregnancy is associated with an increased risk of:
a. Pregnancy complications
b. Adverse pregnancy outcomes
c. Major congenital malformations in the offspring (overall and organ-specific if feasible)
d. Adverse neonatal outcomes
Secondary objectives
?To describe utilization of Spikevax in pregnancy

STUDY DESIGN
The maternal and pregnancy outcomes will be addressed using the prevalence study design; neonatal outcomes and pregnancy related death in the cohort design. In the routinely collected data, pregnancies are typically identifiable on the date of pregnancy end, either in a birth or in an abortive outcome. All identifiable pregnancies will be included, and their start and end dates will be determined based on the LMP or gestational age at end, depending on data availability. Outcomes examined in this design include gestational diabetes, hypertensive disorders of pregnancy, pregnancy-related death, fetal growth restriction/small for gestational age, spontaneous abortion, stillbirth, preterm birth, major congenital malformations, microcephaly, neonatal death, and termination of pregnancy for foetal anomaly (TOPFA).

POPULATION
This study will be multi-database, utilizing routinely collected health data of various types in five European countries: Denmark, Italy, Norway, Spain, and the United Kingdom. Pregnancies ending between 6 January 2021 (date of the earliest approval of the COVID-19 Moderna Vaccine in Europe) and 31 December 2022 will be identified and classified according to the exposure to the COVID-19 Moderna Vaccine, overall and according to the trimester of exposure. The study period may be extended if the size of the study population is insufficient to study specific outcomes of interest.
The study population will encompass all pregnancies, identifiable in the databases, ending in a live or still birth, a spontaneous abortion, or an induced abortion, as identifiable in the participating databases. In Denmark and Norway, all pregnancies ending in a live or still birth, as well as pregnancies leading to a hospital encounter due to termination will be identifiable.

VARIABLES
Members of the analysis populations (pregnancies, births, depending on the outcome) will be described with respect to available demographic characteristics, medical history, medication use, receipt of other vaccines, and characteristics of the exposed pregnancy. Pregnancies and births will be classified according to the exposure status Spikevax, overall and by trimester.
The outcomes of interest will include pregnancy complications, adverse pregnancy outcomes, and adverse neonatal outcomes.
Covariates will include maternal pre-pregnancy demographic and clinical characteristics, such as age, smoking, body mass index, chronic morbidities and medication use.

DATA SORUCES
This study is planned as analysis of routinely collected health data in secondary automated electronic data sources in Denmark, Italy, Norway, Spain, and the UK, selected based on availability of the required routinely collected data, including information on vaccine brand and frequency of data updates.

STUDY SIZE
It is estimated that the number of live births available for analysis will range between 20,000 to 100,000 depending on a data source.

DATA ANALYSIS
Counts and percentages will be presented for categorical variables (woman’s age at conception in categories). Means, standard deviations, medians and interquartile ranges will be presented for continuous variables (woman’s age at conception). The proportion of missing data will be described when appropriate. For pregnancy complications and adverse pregnancy outcomes, pregnancy will be the unit of observation; for neonatal outcomes, a newborn will be the unit of observation. For the outcomes of congenital malformations and stillbirth, the number at risk will be the total number of live or stillborn children.
Prevalence of each outcome will be computed as number of observations with a given outcome divided by the total number of observations at risk. Prevalence of each outcome will be compared for exposed vs. unexposed pregnancies according to predefined exposure categories and using, whenever necessary, plausible exposure risk windows. For example, for assessing the outcome of congenital malformations, maternal gestational diabetes and hypertensive disorders, births or pregnancies will be classified based on their exposure in the first (or second, if relevant) trimester. For all other neonatal outcomes, exposure any time in pregnancy and per trimester may be considered.
For neonatal deaths, 28-day mortality risks will be computed and compared among live-born neonates. For pregnancy-related death, maternal mortality will be evaluated at any time while pregnant or up to 1 year after pregnancy end.
All relevant analyses will be stratified by country, maternal age, sex, calendar time, trimester and seasonality if applicable.

MILESTONES
Data collection will continue through 31 March 2023 with a final study report planned by December 2023.

Background and Rationale
SARS-CoV-2 has spread rapidly and globally since its emergence, causing Coronavirus Disease 2019 (COVID-19). The World Health Organization (WHO) declared that the outbreak constituted a public health emergency of international concern on 30 January 2020 and declared the outbreak to be a pandemic on 11 March 2020. Due to the global spread of COVID-19 pandemic, rapid development of a COVID-19 vaccine is a worldwide priority.
Following the primary analysis of the Phase 3 study COV3001, the United States (US) Food and Drug Administration (FDA) granted an emergency use authorization (EUA) for the Ad26.COV2-S vaccine for use in individuals 18 years of age and older on 27 February 2021. However, following a successful efficacy analysis that supports issuance of an EUA, further evaluation of the Ad26.COV2-S vaccine is still needed, including observational studies that leverage health insurance claims databases and more precise estimation of vaccine effectiveness. Active surveillance of vaccines through additional pharmacovigilance activities such as observational studies should also be considered.
Per communication by the European Commission on October 15, 2020. the Commission has entered into agreements with individual vaccine producers on behalf of the Member States, purchasing and/or reserving the right to purchase vaccine doses under Advance Purchase Agreements. Member States and public health authorities should prepare to undertake studies of vaccine effectiveness and safety via coordination by the European Medicines Agency (EMA) and the European Centre for Disease Prevention and Control, and specifically to prepare for participation in large-scale EU-wide effectiveness and safety monitoring studies. On 11 March 2021, the EMA granted a conditional marketing authorization (CMA) for the Ad26.COV2.S vaccine for use in individuals 18 years of age and older.
To address these regulatory requests, the sponsor plans to initiate a post-authorization safety study (PASS) aiming to characterize and evaluate the safety profile of Ad26.COV2.S in a large population sample size and to inform the scientific community on AESIs that could be associated with the use of Ad26.COV2.S.
Research Question and Objectives
This study has 2 chronologically consecutive aims: 1) to conduct a feasibility assessment aiming to inform the safety evaluation study and 2) to assess the risk of developing pre-specified and newly identified AESIs following administration of Ad26.COV2.S.
Objectives
Feasibility Assessment
The feasibility assessment will include the following objectives (not all objectives may be assessed in all analyses):
?To provide a comprehensive overview of the methods for identification of COVID-19 vaccine exposure including provenance of data and linkage to vaccination registry
?To monitor the number of individuals unexposed to any COVID-19 vaccine and to investigate the risk of misidentification of the COVID-19 vaccine exposure. Both missing vaccination instances and misclassification of the type of vaccine will be assessed with the benchmark provided by: https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-tracker.html#uptake-tab)
?To compare individuals receiving and not receiving different COVID-19 vaccines with respect to demographics and clinical characteristics of recipients and assess potential confounders and risk factors for the AESI
?To conduct time-to-onset analyses for the AESIs (including exacerbation of asthma) with respect to time since vaccination.
Secondary objectives
The secondary objectives for this study are to assess the potential association between the occurrence of predefined and newly identified AESIs and vaccination with Ad26.COV2.S in the following specific subpopulations (part of the main study population):
?Immunocompromised individuals,
?Pregnant women,
?Individuals who have a prior history of thrombotic events and/or thrombocytopenia,
?Prior COVID-19 infection,
?Individuals with a prior history (ever) of the specific event more than a year before start of follow-up.
These results will be compared to COVID-19 vaccine unexposed individuals and, to individuals exposed to other types of COVID-19 vaccines (mRNA or adenovirus-based platforms), or compared to a control window within the same individual.
Endpoints
Feasibility Assessment
The endpoints for the feasibility assessment, including a monitoring phase, are:
?Quality assessment of data that has been extracted from the source data banks (completeness, logics and benchmarking between data sources and against external data)
?The number of doses and uptake of different COVID-19 vaccines by calendar time
?The demographic and morbidity characteristics of individuals receiving the different COVID-19 vaccines as well as non-COVID-19 vaccinated individuals
?Algorithms for AESI identification (including exacerbation of asthma)
?Risk factors for AESI.
Safety Evaluation Study
The primary endpoints for the safety evaluation study are to estimate the risk of the selected AESIs listed below among individuals vaccinated with the Ad26.COV2.S vaccine and in corresponding unexposed individuals and individuals exposed to other types of COVID-19 vaccines (split between mRNA platform-based vaccines and adenovirus-based platforms), or during a control window within the same individual.
The contractual agreements with data partners will stipulate the ability to allow newly identified AESIs to be incorporated into the study objectives, and the current protocol that will be used for governance approvals will state that additional AESI may be added. Each data access provider is responsible to inform the appropriate ethics boards of these amendments.
Acute events (events expected to be recorded within 60 days of vaccination).
?The incidence of anaphylaxis within 0-2 days.
?The incidence of generalized convulsion, arrhythmia, acute kidney failure and acute hepatic failure within 1-14 days.
?The incidence of the following events within 1-28 days.
*thrombotic events (microangiopathy (including capillary leak syndrome), disseminated intravascular coagulation, deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, peripheral thrombosis, thrombosis with thrombocytopenia and ischemic strokes, acute coronary syndrome (acute myocardial infarction, unstable angina, and new episode of angina)
*bleeding events including hemorrhagic stroke (no subarachnoid)
*composite endpoint: Venous thrombosis (including pulmonary embolism and deep vein thrombosis)
*composite endpoint: Arterial thrombosis (including acute coronary syndrome and ischemic stroke)
*composite endpoint: stroke (including hemorrhagic and non-hemorrhagic stroke)
*heart failure, and stress cardiomyopathy.
?The incidence of immune/inflammatory events: encephalitis (including acute demyelinating encephalomyelopathy and meningoencephalitis), Guillain-Barré Syndrome, Bell’s palsy, immune thrombocytopenia, thrombocytopenia, transverse myelitis and cardiac inflammatory disorders (including myocarditis and pericarditis) within 1-42 days.
?The incidence of sensorineural hearing loss within 1-60 days.
Non-acute events (events expected to be recorded >60 days after vaccination)
?The incidence of autoimmune thyroiditis, multiple sclerosis, acute aseptic arthritis, and type 1 diabetes mellitus within 1-365 days.
Newly identified AESI may be incorporated to the list of AESI to be investigated by the current study if a safety signal occurs.
Study Design
The study will comprise a feasibility assessment for a period of 18 months and a safety evaluation study.
This study is a retrospective observational study using electronic health care databases of various types in Europe. Eligible individuals will be included in the study from 01 December 2020, and the study will end at the last date of data availability in each database. The AESIs included in this study are considered as potential or identified safety risks following administration of Ad26.COV2.S. The selected AESIs represent a heterogeneous group including multiple organ systems, and acute and chronic conditions.
Feasibility: A feasibility assessment, focusing on the availability of Ad26.COV2.S vaccine data (vaccine uptake), characteristics of individuals vaccinated with different COVID-19 vaccines and non-vaccinated as well as measurement of AESIs will be conducted for each participating data source. From the start of the feasibility assessment, participating data sources will extract data every 4 months (where possible, it is known already this will not be possible in Norway, where only one extract is done per year). Summary reports will be produced at each extraction (up to 3 rounds of monitoring analyses are foreseen). Primary design for the feasibility assessment will be a cohort study including all individuals with at least one day of follow-up after 01 December 2020.
Safety Evaluation: Evaluation of safety concerns will be conducted using a retrospective observational study in electronic health care databases of various types in Europe. Eligible individuals will be included in the study from 01 December 2020 and the study will end at the last date of data availability in each database.
For each AESI, the study design of the safety evaluation study will depend on whether the AESI is an acute or non-acute event and follow the decision framework described in the ACCESS template protocols for evaluation of safety events in electronic health care databases.
The primary study design for evaluation of acute events (events expected to occur within 2, 14, 28, 42, or 60 days of vaccination) will be a self-controlled risk interval (SCRI) design with a pre-vaccination control window and for non-acute events (events expected to occur within 365 days) will be a cohort design with concurrent unexposed comparators. Additionally, the cohort analysis will also include two active comparator groups: one viral vector vaccine comparator group (ie, Vaxzevria® [AZD1222] by Oxford/AstraZeneca) and one mRNA vaccine comparator group (ie, Comirnaty® [tozinameran] by Pfizer/BioNTech and/or Spikevax® [elasomeran] by Moderna), where possible (pending on the feasibility analysis with a maximum follow-up time of one year).
In sensitivity analyses, an equivalent cohort design will also be used to assess acute events for data sources. When it is established that data sources do not capture vaccinations well during the feasibility assessment, we will conduct a sensitivity analysis excluding these data sources from the cohort analysis with non-exposed comparators for the non-acute events, to avoid misclassification of exposure.
Individuals start follow-up at time zero (cohort entry) and end follow-up at the earliest occurrence of latest data availability of the databank, individual exit from the database, completion of the study period, or death. At least one year of enrollment prior to time zero (cohort entry) will be required to determine whether individuals meet the study criteria and to define baseline characteristics. If more historic data is available, this will be included.
Self-controlled risk interval design (primary study design for acute events)
The SCRI design will compare the risk of the AESI in a post-vaccination risk window to a pre vaccination (interim analyses) and post-vaccination control window (sensitivity analysis) within the same individual. For the final analysis, when enough follow-up is accrued, the main analysis will be the post-vaccination control window.
The SCRI design will include only individuals in the primary analysis who received at least one first ever dose of the Ad26.COV2.S vaccine during the study period. Vaccinated individuals enter study at the date of the start of the pre-vaccination control window (time zero). The SCRI design will compare the risk of each outcome during the post-vaccination risk window following the COVID-19 dose with a self-matched control interval that may be prior to vaccination, or after the vaccination risk window, to assess the baseline risk of the outcome. The control window will have the same maximum length as the risk window to minimize time-varying confounding that cannot be measured. In case the follow-up time does not capture the maximum post-vaccination risk or control -window due to right censoring, all available follow-up time will be utilized. Follow-up will be censored upon vaccination with another COVID-19 vaccine or end of follow-up. A washout period between the control and risk window will be applied to minimize capturing of prevalent events during the risk window. A post vaccination control window may induce a bias towards the null when an AESI that was identified during the vaccination risk window, is captured again during the control window due to a re-admission instead of reoccurrence of the AESI. This situation is more likely to be encountered for acute potentially recurring events such as cardiac events (including acute coronary syndrome, myocarditis, pericarditis, arrhythmia, and stress cardiomyopathy). Moreover, due to lag-times in updating the relevant databanks there is a higher risk that the post-vaccination control window may not capture all events and underestimate the rate of events. Use of a pre-vaccination control window, will deal with these issues. For the interim analyses we will therefore use a pre-vaccination control window as primary analysis, for the final analysis a pre- and post-vaccination control window will be used and analyzed separately.
Cohort design (primary study design and non acute events and sensitivity analysis for acute events)
For the primary analysis of non acute events, a retrospective cohort design will be used to estimate the rate of vaccination with Ad26.COV2.S vaccine, describe the characteristics of these vaccinated individuals and subsequently to estimate the incidence of autoimmune thyroiditis, multiple sclerosis, acute aseptic arthritis, and type 1 diabetes mellitus after receipt of the vaccine dose and to compare this incidence with that occurring in an unvaccinated matched comparator group, and in two groups of individuals exposed to other types of COVID-19 vaccines (ie, one viral vector vaccine comparator group vaccinated (ie, Vaxzevria® [AZD1222] by Oxford/AstraZeneca) and one mRNA vaccine comparator group (ie, Comirnaty® [tozinameran] by Pfizer/BioNTech and Spikevax® [elasomeran] by Moderna).
As a sensitivity analysis for acute events, a cohort analysis (following the same approach used in the main analysis for non-acute events) will be conducted.
?Exposed cohort: individuals will have received at least 1 dose of Ad26.COV2.S.
?Concurrent unexposed cohort: individuals that have not been vaccinated with Ad26.COV2.S vaccine or any other COVID-19 vaccine at any time prior to time zero matched to the vaccinated individual for important characteristics.
?Cohort exposed to other COVID-19 vaccines: individuals will have received at least 1 dose of a viral vector COVID-19 vaccine (ie, Vaxzevria® [AZD1222] by Oxford/AstraZeneca) or an mRNA COVID-19 vaccine (Comirnaty® [tozinameran] by Pfizer/BioNTech and Spikevax® [elasomeran] by Moderna, respectively).
In this retrospective cohort design, time zero (cohort entry) will be defined as the time at which the exposure status is assigned, when selection criteria are applied and when study outcomes start to be counted. Time zero in the exposed cohorts (ie, recipients of the vaccines) will be the day the first dose of the corresponding COVID-19 vaccination was received. Time zero in the unexposed group will be a day when an individual did not receive a COVID-19 vaccine dose and randomly chosen by calendar matching to the time zero of the corresponding Ad26.COV2.S exposed individual (ie, a random day during the same week that the matching individual in the exposed cohort receives the Ad26.COV2.S vaccine).
Individuals in the Ad26.COV2.S exposed cohort will be individually matched to one individual in the concurrent unexposed cohort and to one individual in each active comparator cohorts on key clinical variables (exact age, sex, and presence of one or more risk factors for severe COVID-19 [eg, cancer, sickle cell disease, obesity, chronic kidney disease, chronic respiratory disease, human immunodeficiency virus infection], and month of vaccination (using caliper if needed)) at time zero. Additional details on the matching process will be specified in the statistical analysis plan (SAP). A single individual may contribute person-time to the exposed and unexposed groups at different time points (details will be described in the SAP). Individuals will be classified into exposure groups that are compatible with their data at time zero. Follow-up under unexposed status is censored if an individual receives a COVID-19 vaccine. In a sensitivity analysis, vaccination to other non-COVID 19 vaccines will also be an exclusion and censoring event.
Setting and Study Population
For the implementation of the feasibility assessment, electronic health care databases in Northern, Southern and Western Europe that have showed interest and are member of the Vaccine Monitoring Collaboration for Europe (VAC4EU) will be used.
Feasibility Assessment
For the feasibility assessment, the study period will start on 1 December 2020 or the latest date when the individual is registered in the data source (plus 365 days), or born and will end a maximum of 18 months thereafter. Individuals will be followed until the earliest of the following dates: death, end of data availability, individual exit from the data source, or the completion of the period
Safety Evaluation Study
For the SCRI design, the study period will start at 01 December 2020 and last until the end of follow-up.
For the cohort design, the study period will start at 01 December 2020 and will end at the end of follow-up.
?For the SCRI design, follow-up starts at the start of the pre-vaccination control window following an AESI specific washout period. Follow-up ends at the earliest of the following: death, end of data availability, individual withdrawal of the study, end of the post-vaccination risk or control window, or receipt of another COVID-19 vaccine.
?For the cohort design follow-up starts at time zero (Ad26.COV2.S or other COVID-19 vaccination date or the matched date in the non-exposed individual). Follow-up ends at occurrence of each AESI, death, end of data availability, individual exits the database, after one year of follow-up, receipt of a COVID-19 vaccine (unexposed cohort only), receipt of a different COVID-19 vaccine from the one granting access to the study (exposed cohorts only). For the vaccine exposed comparator groups, a second dose of the same corresponding vaccine will be allowed (more details will be provided in the SAP). In a sensitivity analysis, follow-up in the cohort study will be censored upon receipt of other vaccines (non-COVID-19 vaccine). For the subgroup analysis of subjects without COVID-19 at time zero, patients will be censored if they develop COVID-19 during follow-up.
Variables
Exposure assessment
Exposure will be based on available prescription, dispensing, or administration of the Ad26.COV2.S and other COVID-19 vaccines. Vaccine receipt and date of vaccination will be obtained from all possible sources that capture COVID-19 vaccination, such as pharmacy dispensing records, general practice records, immunization registers, vaccination records, medical records, or other data banks. During the feasibility assessment, the completeness of information will be assessed and described. Depending on the data source, vaccines may be identified via nationally used product codes (including batch numbers) where possible. The exposure of interest for the safety evaluation study is the receipt of Ad26.COV2.S vaccine.
Study outcomes
AESIs, as listed below and in line with the definitions and code lists that for most of the AESI have been created for the ACCESS project (https://zenodo.org/communities/vac4eu/), will be identified, with a date of diagnosis, using predefined validated algorithms (where available), based on diagnosis codes (with procedure and/or pharmacy dispensing codes and/or limited to specific medical care settings if applicable to the outcome). The impact of different provenance of data (hospital, GP diagnoses) and algorithms on the outcome frequency will be assessed and described in the feasibility assessment.
Evaluation of Safety Outcomes
The sponsor has created a list of AESIs based on current knowledge of the Ad26.COV2.S vaccine. Background incidence rates for most of the data sources and AESIs are available on the VAC4EU dashboard https://vac4eu.org/covid-19-tool/. Definitions and codes are available on Zenodo (https://zenodo.org/communities/vac4eu/).
Covariate definition
Feasibility Assessment
In the feasibility assessment covariates will be assessed at the time of COVID-19 vaccine administration or time matched non-vaccinated individuals.
Safety Evaluation Study
Covariate assessment for the description of the patient population at baseline (time zero) will use all available time of enrollment in the corresponding data source (minimum required enrollment period is 1 year).
Covariates will be assessed at time zero (for the cohort design) or the date of vaccine dose (for the SCRI design) to be used to define patient populations of special interest or priority vaccination groups, to define subgroups of interest for sensitivity analyses, or to control for confounding.
We will consider the following time-varying covariates and corresponding period of evaluation for the SCRI measured at start of the risk window and the control window. To capture use of medications of interest during the month prior to start of the study periods (ie, risk control and control risk), we will consider the drug supply covering the month prior to the start of the two periods of interest.
Data Sources
The study will use data from secondary electronic health record databases that are population based. All data sources will have the ability to provide data on COVID-19 vaccines, outcomes (diagnoses, procedures, laboratory results, and treatments), and important covariates. It is not currently known the extent to which COVID-19 vaccines, product types, and batch numbers will be captured in data sources. To be included in the study, data sources should preferably be updated at a minimum once every 3 months. At the proposal stage, members of VAC4EU were offered the option to participate in the study. Seven data sources from 5 countries (Italy, Norway, Spain, The Netherlands, UK) countries will be included in the study. A more detailed description will be included in the VAC4EU FAIR Catalogue.
When establishing the agreements with the data sources to conduct the study, it will be emphasized that the current list of AESIs may be expanded during the course of the study to accommodate newly identified AESIs.
Study Size
The study will be conducted in a source population of approximately 43 million individuals, although children will not be vaccinated. It is assumed that up to 10% will be vaccinated with the Ad26.COV2.S vaccine.
Main Statistical Methods
A general description of the planned statistical methods to be used to analyse the data collected in this study is presented in the main body of the document. Additional details will be provided in the SAP.
For the feasibility analysis the utilization patterns of Ad26.COV2.S and other COVID-19 vaccines will be characterized and monitored over time. Description of demographics and clinical characteristics will be reported for different groups of vaccine recipients and non-recipients, overall and among sub-cohorts of interest, such as individuals who are immunocompromised, pregnant, or have specific comorbidities.
The primary analysis will focus on the calculation and comparison of the incidence rates of each non-acute AESI between individuals exposed to Ad26.COV2.S and
1.unexposed individuals
2.individuals exposed to another viral vector COVID-19 vaccine (ie, Vaxzevria® [AZD1222] by Oxford/AstraZeneca); and
3.individuals exposed receiving a mRNA COVID-19 vaccine (cohort).
For acute events, the relative risk between risk window and control window will be estimated (SCRI) among individuals exposed to Ad26.COV2.S. All analyses will be conducted within each data source and pooled across data sources using a random-effects model.
For the COVID-19 vaccines with a 2-dose schedule, AESI-specific risk windows after each dose of the comparator will be considered for the analyses.
Analyses within the primary study designs (cohort design for non-acute events and SCRI design for acute events) will be stratified by the clinically relevant subgroups below. Stratification will be done also for matching variables when considered relevant.
?Selected comorbidities, including risk factors for severe COVID 19 (by presence or absence of each comorbidity)
?Frailty score (categorized)
?Age ([<18], [18-39]; [40-59]; [60-79], [80+]) ?Sex. Sensitivity analyses will be performed to: ?Assess the risk of AESI within extended disease-specific risk windows for events for which the risk interval is not well known or documented in the vaccine safety literature. ?Assess the impact of data sources that are shown not to capture vaccinations well during the feasibility assessment. In the sensitivity analyses with non-exposed comparators those data sources from the cohort analysis for the acute and non-acute events will be excluded, to avoid misclassification of exposure. ?Excluding and censoring upon occurrence of other (non-COVID-19) vaccinations in the SCRI and cohort study. ?Conduct a SCRI analysis using a post-vaccination control window for all acute AESIs. ?Interim Analysis. Interim analyses may be conducted for all included individuals to generate data for disease-specific time periods (ie, every 4 months).

Objetivos:
Evaluar la efectividad de una aplicación (app) para la abstinencia tabáquica en mujeres gestantes fumadoras. Objetivos específicos: 1)Determinar la efectividad de la intervención sobre la deshabituación del tabaco durante el embarazo, 2)Determinar la efectividad de la intervención a largo plazo (12 meses post intervención) y 3)Determinar la efectividad de la intervención sobre la reducción del tabaquismo en las embarazadas que continúen fumando.
Diseño:
Ensayo aleatorizado, multicéntrico de intervención comunitaria.
Ámbito:
Servicios de Atención a la Salud Sexual y Reproductiva de los Centros de Atención Primaria del Camp de Tarragona y Cataluña Central.
Población de estudio:
mujeres embarazadas que consulten por cualquier motivo, refieran haber fumado los 30 días previos y acepten participar.
Intervención:
todas las participantes recibirán la atención clínica habitual para dejar de fumar, el grupo intervención (GI) además tendrá acceso a una app para dejar de fumar basada en la gamificación. Variable resultado principal: abstinencia autoinformada prolongada, durante el embarazo y tras 12 meses de la intervención, se comprobará mediante coximetria durante el seguimiento y se verificara con test de cotinina al finalizarlo.
Análisis:
de grupos “”por intención de tratar”” se compararán tasas de abstinencia y se evaluarán los factores determinantes mediante estadística multivariante. Resultados esperados: La abstinencia en el GI será >5%, comparado con la práctica habitua

Research question and objectives:
Co-primary:
– To estimate the incidence rates of adverse events of special interest (AESI) in the general population by calendar year and data source over the period 2017 to 2020.
– To estimate the incidence of pregnancy outcomes among pregnant women aged between 12 to 55 years old by calendar year and data source over the period 2017 to 2020.
– To estimate the weekly and monthly incidence rates of COVID-19 (overall and by severity level) in 2020 by data source.
– To estimate the monthly incidence rates of multisystem inflammatory syndrome in children (MIS-C) aged between 0 to 19 years old in 2020 by data source.
Secondary:
– To estimate the incidence rates of AESI in the general population by calendar year, sex, age group, and data source over the period 2017 to 2020.
– To estimate the incidence rates of AESI in the general population by month, sex, age group, and data source over the period 2017 to 2020.
– To estimate the incidence rates of multisystem inflammatory syndrome (MIS-C) in children in 2020 by month, sex, age group, and data source.
– To estimate the prevalence of high-risk medical conditions for developing severe COVID-19 by year and data source over the period 2017 to 2020.
– To estimate the incidence rates of AESI in the at-risk population for developing severe COVID-19 by calendar year, sex, age group, and data source over the period 2017 to 2020.

Study design: A retrospective multi-database dynamic cohort study, conducted during the years 2017 to 2020, including the period of SARS-CoV-2 circulation in Europe until the date of last data availability for each data source.

Population: The study population will include all individuals observed in one of the participating data sources for at least one day during the study period (01 January 2017 – last data availability) and who has at least 1 year of data availability before cohort entry, except for individuals with data available since birth.

Variables:
– Person-time: birth and death dates as well as periods of observation.
– Events: dates of medical and/or procedure and/or prescription/dispensing codes to identify AESI, pregnancy outcomes and at-risk medical conditions.

Antecedents: La depressió puerperal és un trastorn mental amb una prevalença que oscil?la entre el 5 i el 60% al món i que al nostre context s?estima al voltant d?un 12-15%. Tot i que consta evidència científica que mostra els diferents factors de risc associats a la depressió puerperal, alguns investigadors consideren que pot ser útil detectar els factors socials, estils de vida i altres condicions de salut física en les dones que ens ajudin a predir el risc de depressió puerperal per a poder dissenyar programes de prevenció eficaços.
Hipotetitzem que el dèficit de ferro en la dona durant la gestació manifestat com un baix nivell de ferritina sèrica és un factor predictiu per al desenvolupament posterior de depressió puerperal.
Objectiu general: Determinar com i en quin grau els nivells de ferritina sèrica durant la gestació s?associen de forma independent a la incidència de depressió puerperal.
Objectius secundaris: Determinar la prevalença d?anèmia gestacional, de dèficit de ferro i d?incidència de depressió puerperal entre les dones ateses en les consultes de l?atenció primària de Catalunya.
Metodologia: estudi de cohort en l?àmbit de l?Atenció Primària de Catalunya durant el període de l?1 de gener del 2010 a 31 de desembre de 2016. S?inclouran en l?anàlisi les dones que han tingut un embaràs (Z.33) i part (080 ? 084) en el període d?estudi. Es farà un screening de la base de dades a nivell basal i després de forma continua per identificar els casos incidents que s?aniran incloent en la cohort. La data índex serà la primera visita de control de l?embaràs (primer trimestre). El seguiment es definirà fins (a) el diagnòstic de depressió puerperal, (b) tres mesos després del part, (c) final del seguiment (31 de desembre de 2016) o (d) mort. Es consideraran criteris d?exclusió: (a) antecedents d?un trastorn mental greu (Trastorns esquizofrènics (F20.x),Trastorn esquizotímic (F21), Trastorns delirants persistents (F22), Trastorns delirants induïts (F24), Trastorns esquizoafectius (F25), altres trastorns psicòtics no orgànics (F28 y F29), Trastorn bipolar (F31.x), Episodi depressiu greu amb símptomes psicòtics (F32.3), Trastorns depressius greus recurrents (F33) i Trastorn obsessiu compulsiu (F42); (b) mort perinatal. Les variables de resultat: es definirà la depressió puerperal a partir de: (a) codi F53.0: depressió puerperal, (b) qualsevol codi F32 o F33 (depressió major) o F38/F39 trastorns afectius no especificats diagnosticats dins del període de 90 dies després del part. Es defineix l?exposició a través del nivell socioeconòmic (determinat a través de l?índex de privació MEDEA (Domínguez-Berjón. Gac Sanit.2008;22:179-87) i els nivells sèrics de ferritina (1º trimestre i 3º trimestre de gestació). Considerarem nivells baixos de ferritina < 12 ng/mL. Les covariables d?estudi; variables sociodemográfiques: data de naixement, regió de residencia assistida i tipus de localitat (rural <2500 habitants; semiurbana població entre 2500 y 10.000; o urbana > 10.000 habitants), número de fills, tipus de lactància (materna, artificial, mixta), proteïna C reactiva, altres biomarcadors de ferro (transferrina, saturació transferrina). Antecedents patològics: antecedents d?ansietat, depressió, diabetis mellitus tipus 1 i tipus 2, diabetis gestacional, hipertensió arterial, dislipèmia, malalties cròniques, tabaquisme i consum d?alcohol (test AUDIT) i la medicació: suplements de ferro. Totes les covariables seran recollides en el 1º trimestre de gestació.
Anàlisis estadístic: Es calcularan les taxes d?incidència com el nombre d?esdeveniments (nous diagnòstics de depressió puerperal) per 1000 persones-anys segons la presencia de nivells baixos o normals de ferritina sèrica (a) en el primer trimestre o (b) en el tercer trimestre de la gestació.
Resultats esperats: Comprovar com i en quin grau els nivells baixos de ferritina en les gestants, s?associen a major risc de depressió puerperal
Aplicabilitat i rellevància: L?estudi tindrà rellevància a nivell científic , doncs la hipòtesi plantejada, tot i que es basa en resultats científics publicats, no ha estat estudiada en una gran cohort poblacional

L’objectiu de l’estudi és descriure l’ús de dulaglutida en diferent subpoblacions de pacients en diferents països europeus. Per avaluar aquests objectiu es descriurà la freqüència d’us de dulaglutide en la població cataracteritzada per edad, gènere, principals comorbilitats i co-prescripcions en els següents sub-grups d’interés:

– Pacients amb insuficiència renal severa.
– Pacients amb malaltia hepàtica.
– Pacients amb insuficiència cardíaca.
– Pacients amb malatia gastrointestinal severa.
– Nens i adoloscents de menys de 18 anys.
– Pacients a partir de 75 anys.
– Embaràs i dones lactants.

També es vol identificar l’ús fora d’indicació (‘off-label’) de dulaglutide, considerant els errors de prescripció i/o fora d?indicació a les diferents poblacions d?interés.

FUNDAMENTO: Actualmente 2 vacunas antineumocócicas, vacuna polisacárida tricosavalente (VNP23) y vacuna conjugada tridecavalente (VNC13), pueden usarse en adultos. Sin embargo, su efectividad clínica comparativa en la práctica es incierta. Objetivo: Investigar y comparar la efectividad clínica de ambas vacunas para prevenir enfermedad neumocócica invasiva (ENI), neumonía neumocócica (NN) y neumonía total de cualquier etiología (NT) en adultos con distintas condiciones de riesgo (inmunodeficiencia/inmunocompromiso, enfermedad pulmonar/respiratoria crónica, cardiopatía, hepatopatía, nefropatía, diabetes, alcoholismo y/o tabaquismo).

Metodología: Estudio de cohortes de base poblacional, multicéntrico atención primaria (establecimiento de la cohorte) y hospitalaria (ocurrencia de eventos), que incluirá aproximadamente dos millones de personas seguidas prospectivamente durante 24 meses. La cohorte de estudio estará conformada por todas las personas >50 años activas en el Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) de Cataluña (n=2.033.465 a 01/01/2015), clasificados en 3 estratos de riesgo (inmunocomprometidos, inmunocompetentes con otras condiciones de riesgo e inmunocompetentes sin condiciones de riesgo) y recepción o no de VNP23/VNC13 antes del inicio del seguimiento (01/01/2017). El estado vacunal (ninguna vacuna, VNP23, VNC13, VNP23+VNC13) será considerado como una condición variable en el tiempo y la medida del efecto será la ocurrencia de ENI, NN y NT durante el seguimiento. La efectividad vacunal se estimará mediante regresión de Cox, con cálculo de Hazard Ratios ajustados por edad, estrato de riesgo y comorbilidad.