Sara Martínez Torres

PANACEA aims to accelerate the large-scale adoption of a Mediterranean, largely organic and locally sourced diet during the perinatal window (from pregnancy up to 4 months post-partum), empowering not only the women but also their partners, using a community-anchored, digitally-enabled and multi-actor approach that demonstrably improves nutrition, sustainability metrics, and consumer empowerment across three Mediterranean countries. This will be achieved by carrying out a community-level intervention actively engaging health centres, community stakeholders and local farmers.

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.

Antecedents
La higiene de mans es refereix a la pràctica de mantenir les mans netes per prevenir la propagació de malalties. Els tallers sobre higiene de mans són una eina important per educar a la població sobre la importància de mantenir les seves mans netes i saludables.
Objectius
El principal objectiu d’aquest projecte és avaluar l’efectivitat d’una acció formativa ja utilitzada en altres àmbits, que incorpora un dispositiu amb fluorescència per quantificar la qualitat de la higiene de mans amb un taller formatiu dirigit a població adulta per la millora de la promoció i prevenció de la salut.
Metodologia
És un assaig comunitari quasi-experimental. La població d’estudi és població adulta del de Catalunya que assisteixi en els diferents tallers comunitaris d’higiene de mans que es realitzaran dins del marc d’aquest projecte.L’equip d’investigació del projecte s’encarregarà de fer una determinació pre-intervenció de la qualitat de rentat de mans amb un dispositiu que detecta per fluorescència l’àrea de la mà ben rentada. A continuació, es farà una formació educativa sobre la higiene de mans i, posteriorment, determinacions post-intervenció.
Anàlisi estadística
Es calcularan les freqüències i els percentatges de les variables qualitatives, la mitja i desviació estàndard o típiques, els valors màxims i mínims per a les variables quantitatives. Es descriurà el càlcul dels intervals de confiança del 95 % tant per a la mitja com per a altres proporcions. Es realitzarà una anàlisi bivariant per a les variables quantitatives, es calcularan els coeficients de correlació de Pearson i/o regressió lineal.
Resultats esperats
Amb aquest estudi s’espera demostrar l’efectivitat d’una intervenció formativa unida a l’ús d’un dispositiu en la millora de la higiene de mans en població general.

El projecte DigiDiab pilot Spain se centra en la implementació i avaluació del sistema GlucoTab en residències de gent gran i atenció domiciliària a la regió de Camp de Tarragona. GlucoTab és un dispositiu mèdic marcat amb CE de classe IIa, indicat per la gestió digitalitzada i centrada en el pacient de la diabetis en hospitals, residències de gent gran i atenció domiciliària. Aquest dispositiu proporciona assistència en la dosificació d’insulina i suport en la presa de decisions, millorant la seguretat i l’eficàcia del tractament de la diabeti L’objectiu principal és avaluar l’eficàcia del sistema GlucoTab en la gestió de la diabetis tipus 2, mantenint els nivells de glucosa en sang dins del rang objectiu. A més, es busca avaluar la usabilitat, seguretat i rendibilitat del sistema comparat amb les pràctiques actuals.
El GlucoTab és un sistema de suport per a professionals de la salut que proporciona recomanacions automatitzades de dosis d’insulina, ajustant-se a les necessitats variables dels pacients per mantenir la glucosa en sang en el rang objectiu de manera segura. Aquesta tecnologia innovadora té el potencial de millorar la gestió de la diabetis, reduir complicacions i costos associats, i augmentar la satisfacció dels pacients i professionals de la salut.
L’estudi inclou pacients amb diabetis tipus 2 tractats amb insulina basal, amb una durada de tractament de tres mesos. Es realitzaran mesures de resultat primàries i secundàries per avaluar l’eficàcia, seguretat, usabilitat i rendibilitat del sistema. Els resultats de l’estudi proporcionaran dades valuoses per a la implementació a gran escala del sistema GlucoTab en entorns de cura de llarga durada i atenció domiciliària.

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.

Si bien no existe un tratamiento curativo para la demencia, el manejor de los factores de riesgo modificables y las enfermedades metabólica relacionadas con el estilo de vida pueden retrasar el inicio o la progresión de la enfermedad. Por ello, proponemos realizar un análisis exhaustivo de la integración multiómica y estilo de vida para proporcionar información sobre los procesos biológicos que ayudarían a avanzar en la comprensión de la cognición, el deterioro cognitivo y la demencia desde las primera etapas. Este estudio contribuirá a identificar marcadores periféricos y factores clave de progresión de enfermedad, brindando oportunidades para diseñar e implementar estrategias efectivas para abordar el deterioro cognitivo y la demencia. Objetivos: 1) Identificar perfiles de metabolitos circulantes, smallRNAs, bacterias intestinales y marcadores de neurodegeneración asociados con diferencias en la función cognitiva (FC); 2)Integrar los datos previos en una firma multiómica y asociarla a diferencias en FC; 3) Investigar las asociaciones de la puntuación de estilo de vida saludable (HLS), sus componenetes individuales y los patrones de sueño con las diferencias en FC; 4) Investigar la interacción entre las firmas uniómicas y multiómicas con el HLS, sus componentes individuales, los patrones de sueño y las diferencias en la FC; 5) Evaluar si las firmas uniómicas y multiómicas identificadas están asociadas con indicadores de envejecimiento vulnerable derivadas de CT-scan/NMR y 18F-FDG-PET, 6) Evaluar si los factores de estilo de vida y firmas uniómicas y multiómicas generadas en los objetivos anteriores se asocian con cambios en los test neuropsicológicos y NMR/CT-scan (n=150), y en 18F-FDG-PET (n=100) tras 2 años de seguimiento. Para lograr todos estos objetivos, diseñamos un estudio observacional prospectivo realizado sobre 300 sujetos, de 45-80 años, con deterioro cognitivo subjetivo o leve.

«Objetivo principal: Evaluar la efectividad de la intervención SinergiAPS (intervención de auditoría/ retroalimentación centrada en el paciente) en la reducción de hospitalizaciones evitables, y explorar los factores que afectan a su implementación.

Diseño: Ensayo clínico híbrido tipo 1, pragmático, múlticéntrico, abierto, con seguimiento a los 24 meses.

Ámbito, muestra y aleatorización: 118 centros de atención primaria de diversas CCAA de España serán aleatoriamente asignados (ratio 1:1) a dos grupos (control e intervención). El grupo intervención recibirá dos auditorías (basal e intermedia a los 12 meses). Dichas auditorías consistirán en la administración del cuestionario PREOS-PC (que mide la seguridad del paciente en base a las experiencias de los pacientes) a una muestra de 150 pacientes por centro. El grupo intervención recibirá informes de los resultados de ambas auditorías, junto a recursos dirigidos a facilitar el diseño e implementación de planes de acción. La intervención se desplegará a través de la herramienta web SinergiAPS, desarrollada y validada en proyectos previos. El grupo control tendrá acceso a la intervención tras la finalización del ensayo clínico (waitlist).

Variables resultado: Variable principal: tasa de hospitalizaciones evitables (extraída a través de CMBD). Secundarias: seguridad percibida por pacientes (PREOS-PC); cultura de seguridad del paciente percibida por los profesionales (cuestionario MOSPC); eventos adversos experimentados por los sanitarios (cuestionario ad hoc); número de acciones de mejora de seguridad (cuestionario ad hoc). Se realizarán dos evaluaciones: basal, y a los 24 meses.

Evaluación de la implementación: Utilizando como base el modelo CFIR, combinaremos técnicas de investigación cualitativa (30 entrevistas individuales, cuadernos de registro de implementación) y cuantitativa (cuestionarios a profesionales de centros intervención,
nivel de uso de la herramienta web SinergiAPS) para evaluar la implementación de SinergiAPS.
«

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.

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.

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).

? We designed an 8-week, parallel-group, randomized-controlled, dietary intervention trial that will be conducted in 110 adult participants with overweight (BMI 27-29.9 kg/m2) who report routinely eating a Western-style diet and regularly consuming unhealthy snacks. We aim to examine the effect of regular consumption of almonds on changes in innate and adaptive immune system. Secondarily, we will investigate whether changes in microRNAs (miRNAs) mediate the effect of almonds in the metabolic reprogramming of defined immune system components (i.e., innate lymphoid cells and monocytes), as a distinctive stamp in alterations to the homeostasis of nutrients in which nutritional strategies can play a key role. Volunteers will be randomized either to follow their regular Western-style diet substituting unhealthy snacks by 2-serving almonds/day (intervention group) or to follow their Western-style dietary habits including isocaloric snacks (control group). Intervention and control group will be matched by gender (male/female), age (<55 / ?55years) and BMI (<27/ ?27kg/m2).

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