Maria Giner Soriano

Antecedentes y objetivos:
Este estudio busca mejorar la identificación de pacientes en riesgo de eventos adversos relacionados con la medicación potencialmente inapropiada (MPI) en atención primaria. Las prácticas actuales no consideran de forma integral el perfil de exposición, definido por el número, tipo y duración de la exposición a MPI.
Metodología:
Se diseñará una escala de riesgo (alto, medio o bajo) de caídas, fracturas, hospitalizaciones o muerte en función del perfil de exposición a los medicamentos del listado STOPPFall, y se evaluará el impacto de una intervención de toma de decisiones compartidas para la deprescripción. El estudio comprende dos fases: (1) un observacional retrospectivo (2010–2025) con datos de SIDIAP en pacientes de al menos 65 años, donde se analizarán incidencias de eventos adversos y su asociación con MPI mediante cohortes y casos-control anidados, y se elaborará la escala de riesgo; y (2) un ensayo clínico cuasiexperimental en dos centros de salud de Barcelona, con 198 pacientes con riesgo medio o alto de padecer uno de los eventos adversos por las MPI. La intervención constará de una formación sobre decisiones compartidas para pacientes y médicos, con seguimiento de seis meses para medir el efecto en la reducción de MPI y eventos adversos.
Determinaciones:
En el estudio observacional, la variable de exposición será la dispensación de MPI de la lista STOPPFall, creando perfiles según número, tipo y tiempo de exposición en el año previo al evento. Las variables de resultado incluirán hospitalización, mortalidad, caídas y fracturas. Otras variables abarcarán características sociodemográficas, índice de comorbilidad de Charlson, hábitos tóxicos, IMC, fármacos concomitantes, visitas a atención primaria e índice de deprivación socioeconómica, considerando como confusores las patologías y medicamentos asociados a mayor riesgo. En el ensayo cuasiexperimental, la variable de exposición será pertenecer al grupo intervención o control. La variable principal de resultado será la reducción en número o dosis de MPI, y las secundarias incluirán caídas, fracturas, hospitalización y mortalidad. Se recogerán además datos sociodemográficos, hábitos de vida, comorbilidades, medicaciones activas y uso de recursos sanitarios.
Análisis estadístico:
Para el estudio observacional se realizará un análisis descriptivo de variables sociodemográficas y clínicas, así como de la exposición a MPI. Se estimará la incidencia anual de eventos adversos (hospitalización, mortalidad, caídas y fracturas) en cohortes, y se aplicarán estudios de casos y controles anidados mediante emparejamiento (optmatch) y modelos de regresión logística condicional, ajustando por edad, sexo, comorbilidad y otros factores de confusión. En la cohorte de expuestos a MPI, se evaluará el riesgo según número, tipo y tiempo de exposición, clasificando a los pacientes en categorías de riesgo bajo, medio y alto. La comparación de grupos se realizará con Ji-Cuadrado y ANOVA, estableciendo la significación en p<0,05. En el ensayo cuasiexperimental se describirán las variables basales y se compararán los grupos de intervención y control a los seis meses en cuanto a número, tipo y dosis de MPI, así como en caídas, fracturas, hospitalizaciones y mortalidad. Se utilizarán pruebas Ji-Cuadrado y t de Student, y se construirá un modelo de regresión logística para identificar factores asociados con la reducción de la exposición a MPI. Se considerará la intervención efectiva si logra disminuir el número o la dosis prescrita de MPI. Resultados esperados, aplicabilidad y relevancia: Se espera que el proyecto permita identificar a la población mayor en mayor riesgo de eventos adversos mediante una escala de riesgo y que, a través de estrategias de toma de decisiones compartidas, se reduzca el uso de MPI. Esto debería traducirse en una menor frecuencia de caídas, fracturas y hospitalizaciones, con beneficios directos para pacientes y familias, así como en una reducción de los costes sanitarios. Además, la integración de estrategias educativas en la práctica clínica puede establecer un modelo para futuras intervenciones en seguridad farmacológica en personas mayores.

RATIONAL AND BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic, multisystemic, autoimmune, systemic rheumatic disease of clinical and biologic heterogeneity. Given the individual variability in SLE manifestations, there is no single treatment paradigm. A tailored, multidisciplinary strategy is required which needs to be adjusted to patients’ individual clinical manifestations. Anifrolumab, a human monoclonal antibody that binds to subunit 1 of the type 1 interferon receptor (IFNAR1), was developed based on the evidence supporting the role of type 1 interferon pathway in SLE. Anifrolumab was approved via a centralised procedure in the European Union (EU) on 14 February 2022. It is indicated as an add-on therapy for the treatment of adult patients with moderate to severe, active autoantibody SLE, despite standard therapy (EMEA/H/C/004975/0000). As part of the original marketing authorisation application to the European Medicines Agency, AstraZeneca included a proposal to conduct a non-interventional multi-country post-authorisation safety study to characterise the risk of malignancies and serious infections among real-world users of anifrolumab.
RESEARCH QUESTION AND OBJECTIVES: The main research question is to evaluate the risk of malignancies and serious infections among moderate/severe SLE patients who receive anifrolumab compared with a comparable population of moderate/severe SLE patients on standard of care (SOC) who do not initiate anifrolumab.
– Primary objectives
The following objectives pertain to the malignancy outcomes:
1) To estimate the incidence of new malignancies (as a composite outcome) in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
2) To compare hazard rates of new malignancies (as a composite outcome) in moderate/severe SLE patients initiating anifrolumab versus comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
The following objectives pertain to the serious infection outcomes:
3) To estimate the incidence of the first occurrence of a serious infection (as a composite outcome) in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
4) To compare hazard rates of the first occurrence of a serious infection (as a composite outcome) in moderate/severe SLE patients initiating anifrolumab versus comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
– Secondary objectives
The following objective pertain to the malignancy and serious infection outcome cohorts:
5) To describe the demographic and clinical characteristics of patients in each study cohort (malignancy cohort and serious infection cohort) at index date, by exposure status (exposed to anifrolumab vs. exposed to SLE SOC).
The following objectives pertain to the malignancy outcomes:
6) To estimate the incidence of new pre-specified malignancy sub-types (separately) in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
7) To compare hazard rates of new pre-specified malignancy sub-types (separately) in moderate/severe SLE patients initiating anifrolumab versus comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
The following objectives pertain to the serious infection outcomes:
8) To estimate the incidence of serious infection components – infections leading to hospitalisation, infections requiring treatment with intravenous antimicrobials, or infections related to death – in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
9) To estimate the incidence of the first occurrence of opportunistic serious infections, other serious infections, pneumonia (overall), fatal and non-fatal pneumonia (separately) in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
10) To compare hazard rates of the first occurrence of opportunistic serious infections, other serious infections, pneumonia (overall), fatal and non-fatal pneumonia (separately) in moderate/severe SLE patients initiating anifrolumab versus comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC), when feasible (i.e., if sample size allows).
Exploratory objectives
The following objectives pertain to the serious infection outcomes:
11) To estimate the incidence of recurrent infections leading to hospitalisation, in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC).
12) To compare the hazard rates of recurrent infections leading to hospitalisation in moderate/severe SLE patients initiating anifrolumab and in comparable moderate/severe SLE patients who do not initiate anifrolumab (exposed to SLE SOC), when feasible.
STUDY DESIGN: This long-term safety study is a cohort study based on secondary use of data from Denmark, France, Germany, and Spain. The study will start after anifrolumab market launch dates in each of these countries. For malignancies, the study period will end on the 31st of May 2029 and for serious infections it will end on the 31st of May 2025.
This study is based on a prevalent new-user design, i.e., adult patients with a SLE diagnosis, previous exposure to SLE SOC (indicated for moderate to severe SLE), uncontrolled SLE and initiating anifrolumab (exposed to anifrolumab) will be compared with a comparable group of patients who do not initiate anifrolumab (exposed to SLE SOC). Time-based exposure sets will be created to identify comparative study cohorts. Exposure sets will be defined within a time interval (+/- 45 days, [wider time intervals may be considered if matches cannot be obtained using this time window]) of anifrolumab initiation where all comparator members within each set match the anifrolumab exposed patient according to time since first SLE SOC prescription. Additionally, to increase comparability, comparators will be selected taking into account SLE disease activity (uncontrolled SLE despite SOC), disease severity and matched on propensity scores (PS).
Two cohorts will be constructed for the outcomes of interest (a malignancies cohort – for evaluating new malignancies as a composite outcome and for malignancies’ sub-types; and a serious infections cohort – for evaluating serious infections outcomes), considering outcome-specific inclusion and exclusion criteria. In the main analysis, on-treatment definition of exposure will be considered: patients will be considered at risk while exposed to the first anifrolumab treatment (or the SOC treatment for the exposed to SLE SOC group). For the analysis of malignancy outcomes, follow-up will start after a 12-months latency period after the index date and an additional 12-months period at risk (off-drug) will be considered to capture outcomes that might occur after drug cessation.
EXPOSURE VARIABLES: Patients exposed to anifrolumab will be defined by the initiation of anifrolumab (anatomical therapeutic chemical code L04AA51).
SLE SOC patients will be defined by the use of drugs indicated for moderate to severe SLE (in addition to antimalarials and/or low dose corticosteroids): medium to high dose corticosteroids, immunosuppressants (synthetic or biologics [except anifrolumab]), plasmapheresis or intravenous immunoglobulins.
OUTCOME VARIABLES
– Primary outcomes
Malignancies will be defined as the first coded diagnosis for haematological malignancies and solid tumours available in the data sources.
Serious infection will be defined as an infection leading to hospitalisation, use of intravenous antimicrobials or an infection-related death, operationalised as:
Infections leading to hospitalisation: a) infection diagnosis as part of a hospitalisation episode or b) infection diagnosis in primary or secondary care settings up to 7 days before hospitalisation.
• Prescription/administration of intravenous antimicrobials.
• Infection-related death: recorded diagnosis of infection in primary or secondary care settings with record of death within the subsequent month.
– Secondary outcomes
Specific types of malignancies: haematologic, solid and skin malignancies.
Serious infection components: infection leading to hospitalisation, infection requiring treatment with IV antimicrobials and infection-related death.
Serious infection types grouped as opportunistic serious infections, other serious infections, pneumonia (overall), fatal and non-fatal pneumonia (separately)
– Exploratory outcomes
All episodes of infections leading to hospitalisation.
OTHER VARIABLES: The following variables will be used to describe the cohorts’ characteristics and to control for confounding: demographics, lifestyle characteristics, SLE disease history (including measures of disease severity and activity), medical history and comorbidities, healthcare resource utilisation and other risk factors specific for malignancies and/or serious infections.
DATA SOURCES: This study will use secondary data from multiple countries. The final list of data sources is based on a feasibility assessment conducted between June 2022 and January 2023. All data elements for this study will be collected from information routinely recorded in the regional and national data sources of:
– Denmark (Danish National Registries)
– France (National Health Data System)
– Germany (Statutory Health Insurance Claims)
– Spain (Information System for the Development of Primary Care Research)
STUDY SIZE: Study size estimations were carried out for the primary outcomes (serious infections and malignancies) at the meta-analysis level varying four parameters – hazard ratio, standard deviation (SD) of hazard ratio, background estimate of the primary outcome, and matching ratios of exposed:non-exposed patients. Simulations were run to calculate expected power to detect a pre-specified hazard ratio (HR) given an overall sample size; and to get exact sample size estimates to achieve 80% power to detect the pre-specified HR. Three specifications of HR threshold were considered, 1.5, 1.8, and 2.0, along with two pre-specified SD (0.1 and 0.2) of HR to get an effect-distribution in lognormal space within which the true HR lies. The background estimate of incidence of serious infections was varied from 9.6 to 39.8 per 1000 person-years, while the background estimate of incidence of malignancies incidence was varied from 5.26 to 6.31 per 1000 person-years. Matching ratios of exposed to non-exposed patients were specified as 1:1 and 1:3. Achieved power was computed for sample sizes ranging from a total of 500 anifrolumab exposed patients across all study countries to 5000 anifrolumab exposed across all study countries.
Approximately 1,312 anifrolumab exposed patients across all study countries would be necessary to achieve 80% power to detect a true HR of 1.5 (geometric mean of 0.405 in lognormal space) from an effect distribution with 0.2 SD (geometric coefficient of variation of 0.132 in lognormal space) for serious infections outcome. This assumes a matching ratio of 1:3, and background IRs of serious infection of 39.8 per 1000 person years.
Approximately 3,195 anifrolumab exposed patients across all study countries would be necessary to achieve 80% power to detect a true HR of 1.5 (geometric mean of 0.405 in lognormal space) from an effect distribution with 0.2 SD (geometric coefficient of variation of 0.132 in lognormal space) for malignancy outcome. This assumes a matching ratio of 1:3, and background IRs of malignancies of 6.31 per 1000 person years.
STATISTICAL ANALYSES: The data analysis for all the study objectives will be performed separately for each data source and using appropriate study sub-cohorts. In this study, PS adjustment will be performed separately in each data source to control for confounding using a prevalent new user design. First, time-based exposure sets will be defined based on duration of SLE SOC use: for each exposed patient, the time-based exposure set will include all unexposed patients with a similar duration of SLE SOC use as the exposed when they become exposed to anifrolumab. A single time-conditional propensity score model will be fit using all the exposure sets. This model will then be used to compute a time-conditional propensity score for all patients (exposed and unexposed) in each time-based exposure set. Each exposed patient will then be matched with up to three unexposed patients from his time-based exposure set by selecting those patients with the closest time-conditional propensity score. Covariate balance after matching will be assessed by calculating the absolute standardised differences for each variable between the study sub-cohorts.

Antecedents:
L’atenció primària (AP) és la responsable del 85-90% de prescripcions d’antimicrobians, pel que s’han implementat estratègies (PRogrames d’Optimització d’ús d’Antimicrobians (PROA)) per millorar la prescripció antimicrobiana. Les infeccions del tracte urinari són la segona causa més freqüent de prescripció d’antimicrobians, però existeix una manca d’acord sobre la definició i tractament d’aquestes en homes. Actualment existeix discrepància i manca d’evidència sobre quin és el tractament per a la prostatitis aguda bacteriana (PBA) en l’AP.
Hipòtesis:
El tractament antimicrobià en la prostatitis bacteriana aguda (PBA) ha canviat al llarg dels anys i pot optimitzar-se a l’AP.
Objectius:
Descriure el tractament antimicrobià al llarg dels anys, la seva eficàcia, així com la influència dels PROA en la prescripció antimicrobiana de les PBA a l’AP a Catalunya.
Metodologia:
Estudi de cohorts observacional en pacients de l’AP de Catalunya entre 2012-2025. S’inclouran homes >18 anys amb diagnòstic de PBA i >1 prescripció antimicrobiana. Es classificaran segons antimicrobià rebut per avaluar l’eficàcia. S’avaluarà l’impacte dels PROA sobre la selecció d’antimicrobians en PBA.
Determinacions:
La informació s’obtindrà del SIDIAP.
Anàlisi estadística:
– Descriptiva: sèrie temporal 2012-2025 i Alluvial plot.
– Eficàcia i complicacions: Corba de supervivència de Kaplan-Meyer
– Wilcoxon-rank test per comparar l’impacte del PROA.
– Variables contínues es presentaran com mitjanes i desviacions estàndard, variables categòriques com nombres i percentatges. Les estadístiques seran bilaterals i amb significació estadística a p<0,05. Resultats esperats: El tractament antimicrobià en la prostatitis aguda s’ha anat adaptant a les recomanacions de les guies locals en l'atenció primària al llarg dels anys i la prescripció de quinolones ha disminuït. Les fluoroquinolones i cefalosporines com tractament empíric per la PBA presenten la mateixa taxa de curació. Les intervencions PROA resulten en menor exposició a fluoroquinolones i major prescripció d'antimicrobians d'espectre estret. Aplicabilitat i Rellevància: Els resultats d'aquest estudi pretenen proporcionar evidències sobre la selecció d'antimicrobians per la PBA, la seva eficàcia i el paper del PROA a l’AP. Es sol·licita l'extracció de dades d'aquest projecte de manera gratuïta corresponent a l'any 2025 per a Maria Giner Soriano com a membre del Comitè Científic de SIDIAP

Since the advent of biologic agents targeting key proinflammatory pathways, the treatment of chronic inflammatory and autoimmune diseases has substantially changed. Rheumatoid arthritis and psoriasis are two of the most common conditions for which these agents are administered. Patients taking biologics are more prone to mild infections; however, since most trials conducted have been of short duration, long-term follow-up of these individuals is necessary. Their association with serious infections has not yet been thoroughly analyzed.
In response to the need for further investigation into the long-term effects of biologic therapies, we propose a cohort study of patients with rheumatoid arthritis and/or psoriasis, comparing those exposed to biologic drugs with those who have not been exposed. We aim to analyze the association with potentially severe infections, including influenza, sepsis, pneumonia, and COVID-19.
This study aims to evaluate the association between biologic exposure and the incidence of serious infections, including COVID-19, influenza, pneumonia, and/or septicaemia, in patients diagnosed with rheumatoid arthritis and/or psoriasis in the general population of Catalonia.
Specific objectives:
To describe the sociodemographic and clinical characteristics of patients with rheumatoid arthritis and/or psoriasis, including their comorbidities, pharmacological treatments in use, and the prevalence of serious infections in this population.
To evaluate the association between different biologics and the incidence of life-threating infections in patients diagnosed with rheumatoid arthritis and/or psoriasis.
To evaluate the association between the duration of biologic exposure and the incidence of these infections in the same patient population.
To assess the impact of recent biologic exposure (within the last two months) on the incidence of these infections in the same patient population.
To evaluate the impact of comorbidities on the associations between biologic therapy and the incidence of infections in the same patient population.
To determine the influence of concurrent immunosuppressive therapies on biologic exposure and their relationship with the incidence of infections in the same patient population.
Design: Population-based cohort study.
Study period: A ten-years period, from January 1, 2014, to June 2024.
Population: Adult patients diagnosed with rheumatoid arthritis and/or psoriasis treated with biologic and non-biologic therapies will be identified in the primary healthcare records in Catalonia (ECAP), and they will be categorized into different cohorts based on their prior exposure to biologic treatments.
Data analysis:
The study population will be described overall and stratified by exposure status (exposed vs. unexposed individuals). Quantitative variables will be summarized using means with standard deviations (SD) or medians with interquartile ranges (IQR), depending on the distribution of the variable. Categorical variables will be presented as absolute and relative frequencies. Bivariate comparisons between groups will be conducted using Student’s t-tests, Wilcoxon rank-sum tests, or Chi-square tests, as appropriate.
For the primary outcome, marginal structural models (MSMs) will be employed to estimate the risk of treatment exposure while addressing confounding. Inverse probability of treatment weights (IPTWs) will be derived from propensity scores calculated using age, sex, socioeconomic deprivation score, previous life-threatening infections, and other relevant clinical factors. If necessary, weights will be truncated at the 1st percentile to stabilize estimates. Covariate balance before and after weighting will be evaluated using the standardized mean difference (SMD). Variables with SMD > 0.1 after weighting will be included in the MSM as additional covariates to achieve double robustness.
IPTWs will then be applied in logistic regression models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), using robust standard errors (SEs) to account for variability. Statistical significance will be determined using the Wald test at a 0.05 level. When assessing the association between prior biologic exposure and severity outcomes, patients will be assigned to the worst outcome observed (all-cause death > hospitalization > disease presence) to ensure a mutually exclusive classification.
All analyses will be performed using R software (v4.2 or above).

Objetivos: Evaluar la efectividad clínica de 2 pautas antibióticas de fosfomicina: 3 g de fosfomicina trometamol monodosis y 3 g de fosfomicina trometamol una vez al día, 2 días.
Diseño: Estudio observacional con medicamentos (Active comparator New user design that emulates a target trial).
Ámbito de estudio: pacientes de la base de datos de un proyecto previo ITUCAT, que contiene información registrada de pacientes de la base de datos SIDIAP (Sistema de Información para el Desarrollo de la Investigación en Atención Primaria) entre los años 2012-2021.
Población de estudio: Todas las mujeres = de 18 años no embarazadas con diagnóstico de infección urinaria baja no complicada (IUBNC) o cistitis, que hayan iniciado un tratamiento antibiótico en monoterapia con fosfomicina en el período comprendido del estudio y que hayan sido atendidas en alguno de los centros sanitarios del instituto catalán de la salud (ICS) y con registro en la base de datos de SIDIAP.
Variables: necesidad de un segundo antibiótico a los 7 días, a los 14 días y a los 28 días, incidencia de pielonefritis durante los 28 días posteriores a la fecha índice, días hasta la recepción de un segundo antibiótico tras la fecha índice.
Análisis estadístico: Todos los análisis se realizarán mediante el software estadístico R (versión 4.3.1)
Resultados esperados, aplicabilidad, relevancia y limitaciones:
En base a resultados previos se espera encontrar que la fosfomicina 3 g monodosis sea inferior al tratamiento de dos dosis en IUBNC en mujeres adultas. Ante la ausencia de información entre las diferentes pautes antibióticas que se utilizan en Cataluña, este estudio permitirá aportar información de cuál es el tratamiento óptimo para el manejo de las IUBNC. Asimismo, se realizará un target trial emulation que permitirá reducir al máximo los sesgos inherentes a los estudios observacionales. El hecho de que tengamos un número de muestra grande permitirá analizar la efectividad clínica de ambos antibióticos en función de diferentes covariables. Asimismo, este estudio se comparará con el estudio SCOUT para comparar un ensayo clínico con un estudio similar utilizando real world data.
Sin embargo, no debemos obviar que se trata de un estudio observacional y aun cuando, se trata de minimizar al máximo los sesgos, pueden existir debido a que hay variables confusoras que no se conocen y no se pueden tener en consideración en el análisis.
Los datos necesarios para la realización del proyecto se realizarán mediante la reutilización de la base de datos del proyecto ITUCAT. Este proyecto contiene datos de la base de datos SIDIAP (de la historia clínica del ECAP, y del Conjunto Mínimo Básico de Datos (CMBD) de altas hospitalarias (CMBD-AH y de urgencias (CMBD-URG) y datos del registro de medicamentos de dispensación hospitalaria (MHDA).

La insuficiència cardíaca (IC) es classifica habitualment segons la fracció d’ejecció del ventricle esquerre (FEVE), de manera que es diferencien tres fenotips: IC amb FEVE reduïda (ICFEr), quan és = 40%, IC amb FEVE lleugerament reduïda o intermèdia (ICFEmr), quan està entre 41-49%, i IC amb FEVE conservada (ICFEc), si FEVE = 50%. També és habitual utilitzar la classificació funcional de la Nova York Heart Association (NYHA) per a descriure el grau d’IC, basada en la gravetat dels símptomes que presenta el pacient.
L’objectiu del tractament de la IC és reduir la mortalitat, reduir el risc d’hospitalitzacions per descompensació de la malaltia i millorar la simptomatologia. El tractament farmacològic recomanat segons l’evidència científica varia en funció del fenotip de IC.
L’objectiu d’aquest estudi és descriure les característiques clíniques i sociodemogràfiques de les persones diagnosticades de IC i els tractaments farmacològics que s’utilitzen per al maneig de la malaltia.
Recentment hem dut a terme aquest estudi a Catalunya, mitjançant la base de dades de SIDIAP. El nostre objectiu és replicar el mateix estudi amb dades nacionals procedents de BIFAP per a poder comparar els resultats.

La malaltia pulmonar obstructiva crònica (MPOC) és una patologia respiratòria comuna i prevenible, caracteritzada per una obstrucció progressiva i irreversible del flux aeri. El tabaquisme és el principal factor de risc, tot i que hi ha influències ambientals i genètiques. Els símptomes predominants inclouen la dispnea i la tos crònica, i sovint es produeixen exacerbacions que empitjoren la qualitat de vida del pacient. A Catalunya, la prevalença estimada de la MPOC és del 17,3%, la més alta d’Espanya, amb una mortalitat de 37,4 per 100.000 habitants. El diagnòstic i tractament es basa en la classificació GOLD, segons la funció pulmonar (FEV1), i en una estratificació per símptomes i antecedents d’exacerbacions. El tractament farmacològic inclou broncodilatadors de llarga durada (LABA, LAMA) i, en certs casos, corticoides inhalats (CI), especialment en pacients amb eosinofília elevada.
L’objectiu general de l’estudi és caracteritzar l’evolució dels patrons de tractament farmacològics inhalats i els resultats en salut en dues cohorts de pacients amb MPOC (incidents i prevalents) en el sistema sanitari català durant els darrers anys (2019-2024).
Metodologia: Estudi observacional de cohorts de base poblacional. La cohort 1 estarà formada per aquelles persones amb nou diagnòstic de MPOC durant el període d’estudi (diagnòstics incidents). La cohort 2 estarà formada per aquelles persones amb diagnòstic de MPOC actiu en diferents talls transversals durant el període d’estudi (diagnòstics incidents i prevalents).
Anàlisi estadística: El tractament dels registres de medicaments es durà a terme segons el protocol desenvolupat pel grup, basat en l’algorisme smooth.
Els objectius d’estudi s’analitzaran per separat a les dues cohorts. Les anàlisi segons els objectius específics, seran:
1. Descriptiva de les característiques basals en el moment d’entrada a la cohort:
a. Variables categòriques: Freqüències absolutes i relatives (percentatges), comparades entre cohorts amb test ?² o Fisher exacte (si n < 5 per cel·la). b. Variables contínues: Mitjana ± desviació estàndard (distribució normal) o mediana [RIQ] (distribució no normal), comparades amb t-test o Wilcoxon-Mann-Whitney. c. Temps zero: Cohort 1 (data inici tractament), Cohort 2 (01/01/2019). 2. Trajectòries de tractament broncodilatador (Cohort 1): a. Anàlisi longitudinal: Descripció de canvis (inici, monoteràpia, biteràpia, triple teràpia) i discontinuacions mitjançant: b. Diagrames de flux (transicions entre estadis de tractament). 3. Tractament broncodilatador en talls transversals (Cohort 2) a. Prevalences puntuals: Percentatge de pacients en cada estadi de tractament (LABA, LAMA, CI o combinacions d'aquestes) cada 6 mesos (gener/juliol 2019-2024). b. Comparació temporal: Tendències avaluades amb models logístics multinivell (efecte aleatori per pacient) o Cochran-Armitage (tendències lineals). 4. Anàlisi d’aguditzacions/exacerbacions de la MPOC: a. Taxes d’incidència: i. Hospitalitzacions: Nombre d’events/persona-temps (IC95% Poisson). ii. Aguditzacions en AP: Models Poisson/Negative Binomial per sobre-dispersió, ajustats per edat/sex/comorbiditats. b. Comparació entre cohorts: Raons de taxes ajustades (IRR) amb regressió multivariable. 5. Anàlisi de l’impacte de la pandèmia COVID-19 en els pacients de la cohort 2 respecte a canvis de tractament i a morbi-mortalitat. a. Canvis en tractament: Comparació pre/post-pandèmia (març 2020) amb test de McNemar (parellat) i GEE (per a dades longitudinals). b. Morbi-Mortalitat: Comparació pre/post pandèmia. Aplicabilitat i utilitat pràctica dels resultats de l’estudi: Els resultats que s’obtinguin d’aquest estudi seran utilitzats per l’elaboració de futures pautes d’harmonització farmacoterapèutica i/o esquemes de tractament de la MPOC, pel qual seran d’aplicació directa a l’atenció primària.

Aquest estudi preten classificar els pacients de MPOC en dues classificacions: una segons la gravetat (GOLD) i una altra segons trets clínics i biològics (Trets Tractables), per personalitzar millor el tractament. Un cop fetes les classificacions es preten explorar, tractaments administrats i la incidència de noves exacerbacions i mortalitat. Les dades provenen de la base SIDIAP, i tambe´ es busca identificar prescripcions inadequades i desigualtats en l’atencio sanitària.

La falta de adherencia al tratamiento es un problema generalizado en todo el mundo, que conduce a mayores tasas de utilización de los servicios sanitarios e incluso a la muerte prematura.
Aunque el nivel de adherencia puede variar en función de la enfermedad y el tratamiento específicos, los estudios estiman que aproximadamente el 50% de los medicamentos no se toman según las instrucciones prescritas. Las revisiones bibliográficas sobre los factores que afectan a la adherencia de las personas muestran que es difícil predecir quiénes pueden considerarse adherentes o no adherentes. Además, los estudios destacan que es difícil ayudar a una persona a ser adherente. Basándose en estos conocimientos, se creó el proyecto BEAMER (Behavioural and Adherence Model for improving quality, health outcomes and cost-Effectiveness of healthcaRe). El objetivo general del proyecto es mejorar la calidad de vida de las personas, aumentar la accesibilidad y la sostenibilidad de la asistencia sanitaria, transformando así la forma en que los agentes sanitarios se relacionan con los pacientes para conocer su estado de salud y sus niveles de adherencia a lo largo de su recorrido sanitario. Para lograr este objetivo general, el proyecto BEAMER ha desarrollado un modelo agnóstico de la enfermedad denominado «B-COMPASS: BEAMER-COmputational Model for Patient Adherence and Support Solutions». El objetivo de B-COMPASS es identificar las necesidades y preferencias de los pacientes, permitiendo la creación de apoyos específicos para cada paciente, con la intención de mejorar su adherencia al tratamiento dentro de la heterogeneidad de las diferentes áreas de enfermedad y contextos sanitarios.
BEAMER-CAT es un subestudio del proyecto en que se validará la herramienta B-COMPASS en pacientes con patologías prevalentes en atención primaria en tratamiento crónico y, a su vez, evaluará el grado de control de dichas patologáis y el grado de adherencia a los tratamientos.

Rationale and Background: This study will be conducted following the initial marketing authorization of ZEPOSIA® (ozanimod) for the treatment of multiple sclerosis (MS) to observe incidence rates of specific adverse events of interest (AEIs). The AEIs in this Post-Authorisation Safety Study (PASS) were selected based on the mechanism of action of ozanimod (sphingosine 1 phosphate [S1P] receptor modulation), ozanimod nonclinical data, possible class effects and safety issues identified with currently marketed S1P receptor modulator compounds in the MS indication based on AEIs observed in the clinical trials for ozanimod (marketed as ZEPOSIA®).
Research Question and Objectives:
Research question: What are the rates of AEIs in a real-world population of patients with relapsing remitting multiple sclerosis (RRMS) receiving newly marketed product ZEPOSIA® (ozanimod), an oral S1P receptor modulator (exposed) compared to the rates of these events in 2 populations of patients (not exposed to ozanimod) with RRMS who have received treatment with other S1P-receptor modulators or non-S1P receptor disease-modifying treatments (DMTs)?
Primary Objectives: The primary objectives of this study will be carried out through multinational distributed data sources that include secondary databases, such as Optum Research Database (ORD) and Clinical Practice Research Datalink (CPRD) and RRMS cohort and registry data sources in the United Kingdom (UK) and Europe:
•To describe the incidence rate and hazard ratio of major adverse cardiovascular events (MACE) within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used to treat RRMS.
•To describe the incidence rate and hazard ratio of serious opportunistic infections (SOI) within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used in the treatment of RRMS.
•To describe the incidence rate and hazard ratio of serious acute liver injury (SALI) without predisposing risk factors within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used in the treatment of RRMS.
•To describe the incidence rate and hazard ratio of macular edema within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used to treat RRMS.
•To describe the incidence rate and hazard ratio of malignancies within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used to treat RRMS.
•To describe the incidence of acute non-fatal myocardial infarction during exposure to ozanimod and exposure to other therapies used to treat RRMS.
•To describe the incidence of acute non-fatal stroke during exposure to ozanimod and exposure to other therapies used to treat RRMS.
•To describe the incidence of cardiovascular (CV) mortality during exposure to ozanimod and exposure to other therapies used to treat RRMS.
•To evaluate the study outcomes among patients 55 years or older compared to patients younger than 55 years.
Secondary Objectives:
•To describe the incidence of MACE during exposure to ozanimod and exposure to other therapies used to treat RRMS in intervals of time since initiation (ie, < 365 days and = 365 days). •To describe the incidence of symptomatic bradycardia during exposure to ozanimod and exposure to other therapies used to treat RRMS. •To describe the incidence of progressive multifocal leukoencephalopathy (PML) during exposure to ozanimod and exposure to other therapies used to treat RRMS. •To describe the incidence of SALI with and without predisposing factors within the person-time of exposure to ozanimod and the person-time of exposure to other therapies used in the treatment of RRMS. •To describe the incidence rate of posterior reversible encephalopathy syndrome (PRES) during exposure to ozanimod and exposure compared to other therapies used to treat RRMS. Study Design: This is a long-term observational study including patients exposed to ozanimod or other medications used to treat RRMS. The study will use existing multinational distributed data sources, such as administrative healthcare data, electronic health records, and potentially disease registries, which will not be collected primarily for this research but do reflect care in usual clinical practice. Exposure in the automated datasets will be based on prescription or dispensing data. As in usual practice, patients may switch between study drugs, and thus the analysis will be episode-of-use level, rather than patient level. Propensity scores (PS) based on relevant baseline demographics, clinical characteristics, and number of prior treatments at the start of each new treatment episode will be used to adjust for potential confounding in comparative analyses. The primary endpoints of interest are MACE (composite and the individual components of MACE), SOI, and SALI, macular edema, and malignancy. The study will estimate the incidence rates of these events in one exposed (ozanimod), and two comparator cohorts, defined by selected DMTs for MS. Hazard ratios will be considered the main measure of effect. A cohort design will allow direct estimation of the incidence rates, rate differences, and relative risk or hazard ratios of multiple outcomes of interest among new users of ozanimod compared with new users of other DMTs. A cohort study design will also allow accurate chronologic confounder assessment and assessment of the outcomes at multiple time points. The covariate information will be assessed during the time preceding treatment initiation and will include all relevant demographic and clinical characteristics available for each patient. Population(s): The study population will include men and women at least 18 years old who have a diagnosis of MS and are new users of (“initiate”) treatment with one of three cohort-defining treatments. Patients will be grouped into the following cohorts: •Exposed: Starting ozanimod •Non-exposed: Starting another S1P receptor modulator •Non-exposed: Starting a DMT other than an S1P receptor modulator Data Sources: The study cohorts include multinational distributed data sources that will be drawn from electronic databases from health systems in which ozanimod is launched and in countries where reimbursement status is anticipated to be granted or has been granted. The primary sources of data will include the: Optum (USA), Clinical Practice Research Datalink Aurum (UK), GEPARD (Germany), PHARMO (The Netherlands, to be included in the amendment) and SIDIAP (Catalunya, Spain, to be included in the amendment). Study Size: The size of the study cohorts will be determined by the uptake of ozanimod and comparator drugs in the countries and populations included in the data sources during the study period, and the amount of person-time each patient will contribute will depend on how long they remain on specific treatments. Data Analysis: When ozanimod-treated patients reach 1,000 patient-years in at least one data source, the study will conduct the PS-based analyses for the primary objectives in that data source as described below. Selective removal of observations, known as “trimming,” will be implemented at both ends of the PS weight range. At the low end of the range, all patient episodes with a PS weight below the 2.5 percentile value of the distribution of scores in the exposed group (ie, ozanimod) will be excluded. At the upper end of the range, we will exclude all patients, exposed and unexposed to ozanimod, with PS weights greater than the 97.5 percentile.

Antecedentes. La migraña es una cefalea primaria que forma parte de las 20 principales causas de discapacidad a nivel mundial que tiene un impacto en edades productivas afectando el ámbito social, familiar, académico y laboral de las personas. Los efectos de la migraña difieren según sexo/género, la frecuencia, duración e incapacidad que provocan los ataques de migraña son mayores en mujeres que en hombres. Objetivos. El objetivo principal de este estudio es explorar las creencias, actitudes y experiencias de las personas que padecen migraña en relación con el manejo de su enfermedad y de los profesionales sanitarios que las atienden. Métodos. El presente estudio sigue una metodología cualitativa con perspectiva de género y de los determinantes de la salud que investiga las experiencias de dos grupos de participantes: a) participantes del ensayo clínico que padecen migraña y b) profesionales sanitarios que los tratan y hayan reclutado en el ensayo. El reclutamiento será intencional, razonado y de tipo teórico. El estudio se llevará a cabo entre 2025 y 2026 mediante entrevistas semiestructuradas y grupos focales en Atención Primaria de Cataluña. Análisis de datos. Se seguirá el análisis temático de los datos, siguiendo los criterios de Lucy Yardley, así come el COREQ Checklist para asegurar el rigor y la calidad de la investigación. Aplicabilidad y relevancia. Se espera visibilizar las experiencias de las personas que sufren migraña, así como recoger su experiencia con la participación en el ensayo PREMI (NCT06499116) y con la medicación asignada. Además, permitirá recoger las experiencias de profesionales que tratan a pacientes con migraña y su experiencia reclutando para el ensayo. Este estudio permitirá complementar los resultados del ensayo clínico y mejorar el manejo de las personas con migraña en la Atención Primaria.

Las caídas representan una de las principales causas de morbilidad, mortalidad y elevados costes sanitarios a nivel mundial, especialmente en personas de edad avanzada. Se estima que uno de cada tres adultos mayores de 65 años sufre al menos una caída anual, cifra que asciende a uno de cada dos en mayores de 80 años; aproximadamente un 10 % de estas caídas derivan en fracturas, de las cuales cerca de la mitad requieren atención médica.
Paralelamente, la polimedicación y prescripción de psicofármacos en población mayor de 65 años han experimentado un notable incremento en los últimos años, coincidiendo con un aumento de eventos relacionados con caídas y fracturas. Aunque se ha descrito una asociación entre ambos fenómenos, los estudios existentes suelen agrupar los psicofármacos como una única categoría, sin diferenciar el impacto de cada subgrupo específico ni de otros grupos farmacológicos.
Este estudio caso-control doble, basado en datos del mundo real, tiene como objetivo evaluar si el uso de los psicofármacos más prescritos se asocia a un mayor riesgo de caídas —y, en consecuencia, de fracturas—en pacientes de 70 años o más, y determinar si dicho riesgo varía según el tipo de fármaco utilizado.
Se describirán las características sociodemográficas, clínicas y de estilo de vida basales, tanto para la muestra global como estratificadas por presencia o ausencia de caída, utilizando frecuencias absolutas y porcentajes para las variables cualitativas, y medias y desviaciones típicas para las variables cuantitativas.
Los casos y controles se emparejarán mediante puntuaciones de propensión (propensity scores). La asociación entre el diagnóstico de caída y la exposición a fármacos se evaluará mediante razones de Odds (RO), crudas y ajustadas por variables de confusión potenciales, junto con sus intervalos de confianza del 95% (IC95%). Para evaluar la asociación entre fractura y exposición a fármacos, se seleccionarán únicamente los casos. Los casos con fractura se emparejarán con casos sin fractura y, posteriormente, se calcularán las razones de Odds (RO), tanto crudas como ajustadas, junto con sus intervalos de confianza al 95% (IC95%),
para estimar el riesgo de fractura en los individuos expuestos a fármacos en comparación con aquellos no expuestos.

Aquest protocol correspon a un dels “case studies” que es porten a terme dins del “TARGET EU – ROC19: Comparative effectiveness and safety studies using the target trial emulation (TTE) and estimand frameworks”, SIDIAP 640 (reunió Comitè Científic abril 2025), que tenia com a objectiu estudiar la viabilitat de portar estudis de TTE a diferents bases de dades i seleccionar-ne vàries per portar a terme els estudis proposats. Ens han seleccionat per portar a terme el “CASE STUDY 4: Rivaroxaban and risk of major gastrointestinal bleeding in elderly patients with non-valvular atrial fibrillation” que es descriurà a continuació. L’estudi es farà amb el CDM de ConcePTION i reutilitzarem la instància de 31/12/2024.
Background: Non-valvular Atrial fibrillation (NVAF) is a common arrhythmia that presents a significant morbidity and mortality risk. Current evidence suggests important differences in bleeding risk between DOACs that may be particularly relevant in high-risk population, such as the elderly, who tend to be underrepresented in RCTs. The purpose of this study is to compare the safety of apixaban versus rivaroxaban in older adults with NVAF, with a particular focus on major gastrointestinal bleeding.
Objectives: The primary objective is to estimate the effect of initiating rivaroxaban versus apixaban on time to a first major gastrointestinal bleeding event. Methods: We will conduct an active comparator new-user cohort study using linked electronic health records from Denmark (Danish national registers) and Spain (SIDIAP). Eligible individuals are adults (=75 years) who initiated rivaroxaban or apixaban between 2012 (2014 en cas de SIDIAP) and 2023 (o 2024 segons instància actual, a discutir). In the primary analysis, a while on treatment strategy is used for treatment-related intercurrent events (discontinuation, switching). Inverse probability of treatment weighting (IPTW) is used to adjust for confounding. The primary analysis uses a Cox proportional hazards model, with supplemental analyses using an accelerated failure time model to estimate restricted mean survival time (RMST) at 1 and 2 years. Sensitivity analyses will be conducted to assess the impact of changing the conditions related to non-informative censoring using inverse probability of censoring weights as well as outcome misclassification using probabilistic bias analysis. NO CAL EXTRACCIÓ DE DADES. REUTILITZAREM INSTÀNCIA PRÈVIA DEL CDM DE ConcePTION (no omplim l’apartat de variables de SIDIAP).

La insuficiència cardíaca (IC) es classifica habitualment segons la fracció d’ejecció del ventricle esquerre (FEVE), de manera que es diferencien tres fenotips; IC amb FEVE reduïda (IC-FEr), quan és = 40%, IC amb FEVE lleugerament reduïda o intermèdia (IC-FEIr), quan està entre 41-49%, i IC amb FEVE conservada (IC-FEc), si FEVE = 50%. També és habitual utilitzar la classificació funcional de la New York Heart Association (NYHA) per descriure el grau d’IC, basada en la gravetat dels símptomes.
L’objectiu del tractament de la IC és reduir la mortalitat, reduir el risc d’hospitalitzacions per descompensació de la malaltia i millorar la simptomatologia. El tractament farmacològic recomanat segons l’evidència científica varia segons el fenotip d’IC.
L’objectiu d’aquest estudi és classificar els pacients amb diagnòstic d’IC segons la FEVE i descriure les característiques clíniques i sociodemogràfiques d’aquestes persones diagnosticades d’IC i els tractaments farmacològics que s’utilitzen pel maneig de la malaltia.
Es portarà a terme un estudi de cohort amb la base de dades de SIDIAP que inclourà totes les persones amb diagnòstic d’IC a ECAP en el període de 2018 a 2022. Els pacients es classificaran segons la disponibilitat de registre de FEVE i de NYHA a ECAP, i es descriuran les seves característiques sociodemogràfiques i clíniques, a més del tractament farmacològic pel maneig de la IC.
Estem treballant en aquest estudi des de novembre de 2022 i ara sol·licitem les mateixes dades en format OMOP per replicar l’estudi.

Rationale and background: The increasing use of medicines during pregnancy, coupled with a notable lack of safety information for a substantial portion of approved medicines, raises concerns regarding potential teratogenic and neurodevelopmental effects on the fetus. Certain medications with documented long-term teratogenic and neurodevelopmental effects on human fetuses have similarly demonstrated teratogenicity in animal studies. Such correlations emphasize the potential utility of embryo-fetal developmental toxicity (EFDT) studies in identifying medications with lasting effects on children after prenatal exposure. The Dutch National Institute for Public Health and the Environment (RIVM) and the Dutch Medicines Evaluation Board (CBG-MEB) compiled a database comprising rat and rabbit EFDT study outcomes, encompassing 198 European Union (EU) authorized human medicines. This database was used to rank medicines of increased concern, lower concern or minor concern based on malformations and/or embryo-fetal death (MEFL) and exposure safety margins compared to the maximum recommended human dose. In the ConcePTION project, we investigate the long-term effects on offspring after exposure to medications during pregnancy and lactation. Combining data from the animal studies and medication use prevalence data from pregnant women and women of childbearing age could help in prioritizing medicines that pose clinically relevant risk during pregnancy and facilitate the creation of a ranking list for future pharmaco-epidemiological studies.

Research question and objectives: What is the prevalence of prescriptions of medicines known to be associated with developmental toxicity in pregnant women and women of childbearing age?
Primary objectives:
1A. To determine the prevalence of medication use known to be associated with
developmental toxicity in pregnant women, by trimester of pregnancy.
1B. To determine the prevalence of medication use known to be associated with developmental
toxicity in women of childbearing age, by age of the women.
Secondary objective:
2A. To combine medication use prevalence data with pre-clinical data of rat and rabbit teratogens to make a ranking list of medicines known to be associated with developmental toxicity that have a high prevalence of prescription to humans.

Study design: A descriptive retrospective, multi-database cohort study will be conducted.

Population:
The target population will comprise all pregnant women and women of childbearing age registered in the participating data sources between 1 January 2015 – 31 December 2020. The index date for each pregnant women will be the start date of pregnancy. Follow-up continues until end of pregnancy (spontaneous or induced abortion, stillbirth or livebirth). Women of childbearing age will be followed each respective calendar year (2015 till 2020). The follow-up starts at 1 January and ends on 31 December or upon death, migration, becoming pregnant, performing sterilisation, or end of data availability, whichever occurs earliest.

Variables: The ConcePTION algorithm will be used to identify pregnancies. The primary outcome of interest is the prevalence of prescriptions of medicines known to be associated with developmental toxicity. All medicines use refers to prescribed or dispensed medicines as recorded in the participating data sources. All medicines will be identified by Anatomical Therapeutic Chemical (ATC) code. Pregnant women will be considered exposed to the medicines if they received at least one prescription during pregnancy. Women of childbearing age will be considered exposed to the medicines if they had received at least one prescription during follow-up.

Data sources: This study will include data from 4 national healthcare databases in 3 European countries (Italy, Spain, UK), pending feasibility and confirmation.
Study size: The study will include all pregnant women and women of childbearing age identified in the participating data source over a 5 years’ time span.

Data analysis: For objective 1, the prevalence of the medicines of interest will be computed for each data source stratified by trimester of pregnancy. Prevalence will be calculated per 1000 pregnancies with 95% confidence interval. To calculate the prevalence, the numerator will be the number of women having one or more prescription of the specific medicine within a given trimester. The denominator will be the number of women contributing to that trimester. For objective 2, the prevalence of the medicines of interest will be computed for each data source stratified by age. To calculate the prevalence, the numerator will be the number of women having one or more prescription of the specific individual medicines within the given study-period. The denominator will be the total number of women contributing at least one day of person-time to that study period. A sensitivity analysis with >1 prescription will be conducted in both cohorts.

We will use a previous data instance of the ConcePTION CDM, so no new data extraction is needed.

Objetivos: Analizar la asociación entre las medicaciones potencialmente inadecuadas (MPI) de la herramienta STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) y los eventos adversos (hospitalizaciones, mortalidad general, caídas, fracturas y demencia) en atención primaria.
Material y métodos: Estudio de cohortes retrospectivo y de casos-control anidado del 2010 al 2024 usando datos anonimizados de la base de datos SIDIAP (www.sidiap.org) que recoge información médica de atención primaria de >5.8 millones de sujetos (75% de los centros de salud de Cataluña). Los = 65 años, con = 365 días de seguimiento previo y sin ninguno de los eventos adversos a estudio, serán incluidos en las cohortes de 1. Expuestos a MPI (=1 dispensación durante el periodo de estudio) o 2. No expuestos a MPI (en ningún momento dado). Para los estudios casos-control, los casos serán aquellos con un primer evento adverso (hospitalización, mortalidad general, caídas, fracturas o demencia) durante el periodo de estudio. Se emparejarán con controles mediante el procedimiento “optmatch”, por edad, sexo, índice de comorbilidad de Charlson (ICC) y número de medicaciones (excepto MPI). Seguimiento: desde su entrada en la cohorte, inicio del estudio o primera dispensación de MPI (cohorte de expuestos), hasta el evento adverso, fin del estudio, traslado a otro centro o 1 año de seguimiento.Variables de exposición: MPI del listado STOPPFall (benzodiacepinas e hipnóticos, antipsicóticos, opioides, antidepresivos, anticolinérgicos, antiepilépticos, diuréticos, bloqueadores alfa, antihipertensivos centrales, antihistamínicos, vasodilatadores usados en enfermedad cardiaca, medicaciones para la incontinencia urinaria). Variables de resultado: primer registro de hospitalización, mortalidad general, caída, fractura o demencia. Otras variables: datos sociodemográficos, hábitos tóxicos (alcohol y tabaco), índice de masa corporal, número/tipo de MPI, índice de deprivación socioeconómica (MEDEA), visitas en atención primaria (año previo), comorbilidades y medicaciones identificadas como confusoras. Se calculará el porcentaje de exposición a MPI: baja (<25%), media (25-74%) o alta (=75%). Análisis estadístico: Se calculará la incidencia anual total y para cada MPI de los eventos adversos por cada 100 000 personas-año, con intervalo de confianza 95% (IC 95%). Se determinará (regresión logística) el riesgo del evento adverso entre expuestos y no expuestos y en función del porcentaje de exposición a MPI comparado con sujetos con una exposición baja (<25%) (referencia). Las ODDs Ratio, con IC 95%, se ajustarán por edad, sexo, estatus socioeconómico y factores confusores. Los resultados se estratificarán por edad, sexo y estatus socioeconómico. La significación estadística se establecerá en p-valor<0,05. El análisis estadístico se realizará con el programa STATA MP/18 (StataCorp, Texas, USA) y el programa R 4.3.3. Aplicabilidad de los resultados esperados: Los resultados permitirán caracterizar e identificar la población con más riesgo de sufrir eventos adversos debidos a la MPI y determinará si existen diferencias por género en la incidencia de estos eventos adversos.

Les infeccions del tracte urinari (ITU) representen la segona patologia infecciosa més freqüent en atenció primària. El seu maneig ha estat el motiu de molts estudis, però fins a la data no s’ha avaluat la idoneïtat del seu maneig a la totalitat de l’àrea de Catalunya.
Aquest projecte està compost de quatre subprojectes, que es desenvoluparan en 3 fases:
1) Conèixer l’epidemiologia dels diferents tipus d’ITU i el seu maneig terapèutic i demanda d’urocultius;
2) Avaluar la correlació de consum total i tipus d’antibiòtics per a ITUs de repetició amb la presència i gravetat de complicacions infeccioses d’origen urològic, especialment pielonefritis i sepsis, i dues infeccions potencialment greus: pneumònia i COVID-19;
3) Crear una escala predictora associada al diagnòstic d’ITU que es complica en una pielonefritis aguda; i
4) Conèixer el grau d’(in)adequació en la sol·licitud d’urocultius en base a les guies de pràctica clínica.
En la primera fase, que correspon aquesta sol·licitud, s’inclou els objectius 1 i 2.

En aquesta sol·licitud es vol demanar les dades per dur a terme el punt 3 (fase 3 del projecte ITUCAT que té concedit un PERIS).

Hipòtesis: un percentatge de les infeccions del tracte urinari (ITUs) es compliquen, essent la pielonefritis aguda (PNA) la complicació més freqüent. Aquesta pot esdevenir greu en un petit percentatge de casos, però es desconeixen les raons perquè això ocorri.

Objectius de l’estudi: crear una escala predictora de PNA per aquells pacients que siguin diagnosticats d’ITU.

Disseny: estudi observacional.

Àmbit d’estudi: tots els pacients, dones i homes, = 18 anys atesos en els centres sanitaris de l’ICS amb registre en la base de SIDIAP de Catalunya.

Subjectes d’estudi: tots els pacients, dones i homes, = 18 anys atesos en els centres sanitaris de l’ICS amb registre en la base de SIDIAP de Catalunya amb diagnòstic d’ITU entre 2017 – 2021. Segons la base de dades del WP previs del projecte ITUCAT, tenim 1000 homes i 3000 dones que desenvolupa una PNA després d’una cistitis. Atès que es vol realitzar un estudi cas i control (1:2), serà necessari un grup control (2000 homes i 6000 dones).

Variables més importants: variables sociodemogràfiques, clíniques, analítiques, tractaments prescrits/facturats, sol·licitud d’urocultiu, text MEAP.

Anàlisi estadística: el procés de gestió de dades, depuració, càlcul de descriptius i anàlisis estadístics es realitzarà mitjançant el programari estadístic R. Caracteritzarem la població i els grups d’estudi segons les variables demogràfiques i clíniques d’interès. S’avaluaran els possibles factors de risc associats a la pielonefritis a partir de tests bivariats i de la SMD (diferència de mitjanes estandaritzada) entre casos i controls. Posteriorment, s’ajustaran models de regressió logística multivariant ajustant pels factors de risc més rellevants segons criteris clínics i estadístics. Per evitar possibles efectes de col·linealitat, principalment en aquelles variables relacionades amb l’activitat sexual i les d’historial d’ITU, emplenarem el mètode de selecció de variables forward stepwise. Partint del model buit, s’anirà afegint seqüencialment aquelles variables que més contribueixen a l’àrea sota la corba operativa del receptor (ROC), segons l’augment observat de la bondat d’ajust i la significança obtinguda en la prova d’Hosmer-Lemeshow. Examinarem el model final en quatre subgrups d’interès: a) dos subgrups d’edat (edat = 50 anys i edat > 50 anys); b) individus que no reportin antecedents d’ITU i els que sí; c) homes vs dones i d) pacients hospitalitzats greus o no. El model final expressarà l’efecte relatiu de cada factor de risc en termes de odds ratio (OR) amb el seu interval de confiança calculat a partir dels errors estàndard robustos

Resultats esperats, aplicabilitat, rellevància i limitacions: Esperem crear una escala predictora que ajudi als clínics identificar les situacions en que les ITUs poden complicar-se en pielonefritis aguda. Amb això podrem detectar quina o quines variables clíniques i quin diferent test es presenten més freqüentment en les persones adultes que pateixen una pielonefritis aguda en el context d’ITU inicial per poder crear una escala predictiva de pielonefritis que ingressa a l’hospital. Es valorarà la necessitat de crear una escala predictora per a homes i una altra per a dones

Atès que es tracta d’un estudi observacional no permetrà l’anàlisi de la causalitat. A més pot haver presència de possibles variables confusores, que son inherents als estudis de caràcter observacional, com per exemple diagnòstic-tractament no lligats.

RATIONALE AND BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Abrocitinib received marketing authorization for the European Union (EU) on 09 December 2021 and is indicated for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. To mitigate the risks associated with abrocitinib, required routine RMMs including the SmPC and package leaflet are being employed. In addition to the routine RMMs, additional RMMs (aRMMs) inclulding prescriber’s brochure and patient card, are being implemented in the EU.
RESEARCH QUESTION AND OBJECTIVES: The study objectives are to evaluate, to the extent measurable in the available routinely collected data, indicators of HCPs’ adherence to the RMMs in accordance with the abrocitinib SmPC and prescriber’s brochure, assessed by:
– indicators of adherence to performing laboratory tests of CBC, lipid panel, hepatitis B/C, and TB screening prior to initiation of abrocitinib treatment,
– indicators of adherence to performing laboratory tests of CBC and lipid panel at week 4 (±2 weeks) after initiation of abrocitinib treatment,
– indicators of adherence to consideration of risk factors for VTE, MACE, malignancy and serious infection prior to treatment with abrocitinib,
– indicators of adherence to avoid live attenuated vaccines immediately prior to and during treatment with abrocitinib,
– indicators of adherence to contrainidcations for use during pregnancy,
– indicators of adherence to contraindications for use amog patients with severe hepatic impairment,
– indicators of adherence to no use in patients aged < 18 years, and - indicators of adherence to recommended posology (estimated average daily dose). STUDY DESIGN: This will be a descriptive drug utilization study using secondary data from healthcare databases in Denmark, France, Sweden, Spain and Hungary. POPULATION: The study population will include patients with a dispensing of abrocitinib as recorded in routinely collected electronic healthcare data in Denmark, France, Sweden, Spain and Hungary during the study period (study start: country-specific aRMM distribution [01 March 2022, Sweden; 09 March 2022, Denmark; 31 July 2022, France; 30 Jan 2023, Spain; September 2023 (estimated), Hungary]; study end: December 2026). These countries have universal healthcare. VARIABLES: The study will collect all relevant data including patient demographics, comorbidities, prescription medications, vaccine administration, and laboratory testing prior to the initiation of abrocitinib and during treatment with abrocitinib to address the study objectives. DATA SOURCES: This study will utilize routinely collected electronic healthcare data from national or regional population-based electronic healthcare registers in Denmark, Sweden and Spain and an administrative healthcare databases in France and Hungary. STUDY SIZE: All patients initiating abrocitinib during the study period will be included. DATA ANALYSIS: Data will be analysed in each country separately using a common protocol, database-specific definitions of the study variable, and common analysis strategy. The main indicators will be proportions of abrocitinib users with a given indicator of aRMM adherence.

This tender is composed of two objectives:
1. Objective 1: To describe utilisation of antiepileptics in individuals of childbearing age, pregnant, and male individuals. This objective will be described in WorkPackage (WP) 1. There is a specific protocol for WP1. The development of WP1 protocol is one of the deliverables of the project.
2. Objective 2: To assess the feasibility of estimating the risk of adverse pregnancy, neonatal and child outcomes following in utero and paternal exposures to antiepileptic drugs. This objective will be assessed in WP2. Initially, only databases with developed father-child linkage developed were expected to participate. In the end, EMA required all databases involved in WP1 to participate also in WP2. WP2 does not require a data extraction, as it will answer the question whether data sources are fit for purpose for studies assessing adverse pregnancy, neonatal and child outcomes following either ASM exposure through the mother, or periconceptional ASM exposure through the father. There is a specific protocol for WP2. The development of WP2 protocol is one of the deliverables of the project.
Prototol 1 – WP1: THE UTILISATION OF ANTISEIZURE MEDICATIONS IN MEN, WOMEN OF CHILDBEARING AGE, AND PREGNANT WOMEN: A MULTI-DATABASE STUDY FROM 7 EUROPEAN COUNTRIES.
Background: Currently there is substantial evidence on teratogenicity of several antiseizure medications (ASMs) and a potential increased risk of neurodevelopmental disorders in young children exposed in utero to ASMs. Recently, few evidence has emerged expanding this risk also when there was a paternal exposure before conception. On that line, EMA asked for an updated evaluation on trends in use of various ASMs and related drugs in pregnant women, in other women of childbearing potential, and in men.
Objectives: The main objective of this study is to describe the utilisation of ASMs and related drugs (i.e., antiepileptics (ATC codes N03A), gabapentinoids (N02BF), and all benzodiazepines with antiepileptic properties) in pregnant women, other women of childbearing potential (12-55 years of age), and men (12 years and older). It has the following sub-objectives: 1.1) To estimate the annual incidence and prevalence rate of ASM use in women of childbearing potential and in men; 1.2) To describe treatment duration, discontinuation, and treatment switches to other ASMs or alternative medications and polytherapy in women of childbearing potential and men; 1.3) To estimate incidence and prevalence of specific ASM use in up to one year prior to and during the pregnancy period in all pregnant women; 1.4) To estimate and compare discontinuation, treatment switches to other ASMs or alternative medications and polytherapy among pregnant women in the 12-10, 9-7, 6-4, and 3 months prior to pregnancy or during first, second and third pregnancy trimesters; 1.5) To estimate dose changes of ASMs in women prior to and during pregnancy.
Study Design: Retrospective population-based cohort study.
Exposure and outcomes: The main exposures of interest are ASMs (N03A), including gabapentinoids (N02BF) and benzodiazepines with antiepileptic properties. The drug utilisation outcome measures will be the incidence and prevalence of ASM use among pregnant women, other women of childbearing potential, and men, treatment duration of ASM, discontinuation of ASMs, initiation of ASM use during pregnancy, switching to another ASM or an alternative medication, dose changes of ASMs before and during pregnancy, and polytherapy of ASMs.
Data Analysis: According to sub-objectives stated above, statistical estimates will be produced, such as descriptives (counts, percentages), distributions (mean, percentiles), rates (incidence, prevalence), or other relevant estimates. Various visualisations (e.g., flow diagrams, line and bar charts, and Sankey diagrams) will be used to depict the findings. This will be conducted using a common R script.
Limitations: Our operational definitions of treatment episodes with a grace period of 30 days, temporary break (between 30-120 days of no new prescription/dispensing), ASM discontinuation (no new record after 90 days), and switching from an ASM to another ASM or an alternative medicine might not reflect the exact clinical scenarios in case of all ASMs, especially when using data from diverse EHDs. One especial case would be misclassification of prevalent users as incident users due to considering not long enough look-back periods. Due to this, we will not estimate incident use of ASMs among women and men of childbearing potential and initiation of ASM during pregnancy in data sources EFEMERIS and THL that we only have 2.5 or 3-months look-back data for medications. But the overall approach is based on prior drug utilisation studies on the same topic,8,28 and same definitions for all ASMs across all centres, which considering the limitations and data quality will assist in comparability of findings. Another limitation could be operational definitions for high, medium, and low daily doses of ASMs based on DDD data, which might not always reflect the actual clinical situation. But considering the diversity of data sources and healthcare systems involved, this seems the only feasible option in such a multi-database study. Also, capturing the right doses would be difficult when prescriptions are not renewed but patients were using the old prescription with new instructions from clinician, which is not visible in all our included data sources. This will be taken into account when interpreting findings from the dose analyses.
Protocol 2 – WP2: FEASIBILITY OF ESTIMATING THE RISK OF ADVERSE PREGNANCY, NEONATAL AND CHILD OUTCOMES FOLLOWING EITHER IN UTERO ASM EXPOSURE THROUGH THE MOTHER, OR PERI-CONCEPTIONAL ASM EXPOSURE THROUGH THE FATHER
Rationale and background: Evidence shows that certain ASMs such as valproate, pose teratogenic and neurodevelopmental risks during pregnancy. Conflicting findings also suggest potential neurodevelopmental impacts from paternal ASM exposure pre-conception. Thus, it is critical to assess the feasibility of causal studies on ASM exposure, especially given the complexity of father-child data linkage.
Research question and objectives: This study aims to understand whether data sources can be used to study the effects of maternal and paternal exposure to ASM, on pregnancy, neonatal and child outcomes. For this main objective, the following sub-objectives will be addressed:
a. To estimate the availability of relevant information/characteristics for pregnant women, using 15 different parameters that will inform the assessment of fitness for purpose.
b. To estimate availability of relevant information/characteristics for men and linkage with pregnancies, using 9 different parameters that will inform the assessment of fitness for purpose.
c. To estimate availability of relevant information/characteristics for neonates/children, using 17 parameters and comparing them between those that can and cannot be linked to mother and/or father where possible.
d. To assess fitness for purpose to different types of studies of pre-conceptional/prenatal exposure to antiepileptics and the development of adverse pregnancy and child outcomes.
Study design: This is a retrospective cohort study to assess the suitability of the available databases for ASM exposure studies, aligning with the study’s fit for purpose evaluation.
Population: The source population comprises all persons of childbearing age who are registered with the data sources that participate in this study. From the source population, we will select study cohorts for each of the different sub-objectives.
Variables: The main exposures of interest are ASMs (N03A) and gabapentinoids (with ATC code N02BF) and all benzodiazepines with antiepileptic properties. Outcome parameters will be considered per subobjective. Clinical outcomes of interest will include pregnancy outcomes (i.e., spontaneous pregnancy loss, stillbirth, preterm birth) neonatal/child outcomes (e.g., small gestational age, congenital anomalies, adverse neurodevelopment).
WP2 does not require a data extraction, as it is a study to assess the fit for purpose of the databases for assessing adverse pregnancy, neonatal and child outcomes following either ASM exposure through the mother or periconceptional ASM exposure through the father.
Data analysis: For objective a-c we will estimate the 41 feasibility parameters using descriptive analyses and visualizations. For objective d, we will use the parameters from objectives a-c plus metadata on the data sources and assess the fitness-for-purpose of the data instance by using, implementing, and adapting the framework from Gatto and colleagues.
Limitations: Methods for descriptive analysis have been employed in previous studies undertaken across the ConcePTION project, EU PE&PV and VAC4EU networks (Durán et al., 2023a; Hurley et al., 2023; Abtahi et al., 2023; Durán et al., 2023b). This protocol aims to leverage existing tools available tools and algorithms, developed by the aforementioned enterprises, including the ConcePTION CDM, the pregnancy algorithm, the INSIGHT quality checks, code lists and algorithms, as well as component analyses and the analytical pipeline and functions. Differences between data sources will be described transparently. The aim is to describe and appraise mother-child and father-child linkage, both deterministic and probabilistic, that has been established thus far across each data source. We also aim to investigate novel improvement in linkage using additional parameters available in EHR data. It is possible that improvements in probabilistic linkage will not be possible due to characteristics of available data fields, or because linkage will not improve materially with inclusion of these additional data fields. Exploration of parental linkage will be described transparently, regardless of whether improvement in linkage is possible. Due to limited budget and the scope of work, we will not be able to validate any of the linkages nor outcomes.

“La malaltia renal crònica (MRC) engloba un conjunt de malalties i implica la presència d’alteració estructural o de la funció renal. És un problema important de salut pública i s’estima la seva prevalença en el nostre medi d’entre el 7 i 15%. El seu maneig es dur a terme principalment en atenció primaria i el seu objectiu és prevenir i alentir la progressió d’aquesta malaltia tot reduint el risc de malaltia cardiovascular i de complicacions associades. Es basa en mesures higiènico-dietètiques i el tractament farmacològic dels factors de progressió de la MRC i del risc cardiovascular, com també del risc de complicacions de la malaltia.
El tractament dels factors de risc per la MRC inclou el maneig de la hipertensió arterial (HTA), la diabetis mellitus (DM), la dislipèmia (DLP), la hiperuricèmia, l’anèmia, l’obesitat, el virus de l’hepatitis C (VHC), les alteracions del metabolisme ossi i mineral (hormona paratiroidea i la hiperfosfatèmia), la hiperpotassèmia, l’acidosi metabòlica i les complicacions trombòtiques com l’ictus cardioembòlic.
Atès que la MRC és un problema sanitari molt important cal disposar d’informació per conèixer les pràctiques clíniques existents en relació amb el tractament de la MRC a Catalunya i per identificar possibles àrees de millora en el maneig terapèutic de la malaltia.
L’objectiu principal de l’estudi és descriure les característiques i la utilització dels diferents tractaments farmacològics de la població de pacients amb MRC de Catalunya. Com a objectius secundaris es pretén descriure les característiques sociodemogràfiques, clíniques i comorbiditats de la població amb MRC; Descriure la utilització del tractament farmacològic de la població diagnosticada de MRC segons les comorbiditats més importants (HTA, DM tipus 2 i malaltia nefrològica); Descriure la utilització del tractament farmacològic de la població amb MRC segons FG i finalment analitzar la utilització dels fàrmacs segons albuminúria.
Per fer-ho es realitzarà un estudi de cohorts que inclou pacients amb MRC entre en el període de 2018-2022.”

La migranya és un trastorn neurològic que afecta a un 15% de la població adulta, sent la setena malaltia més prevalent al món. És una cefalea primària que es caracteritza per episodis de dolor al cap d’entre 4 i 72 hores de durada.
Per al tractament simptomàtic agut de la migranya habitualment s’utilitzen antiinflamatoris no esteroidals, paracetamol, metamizol, triptans i derivats ergòtics. En 2022 s’han autoritzat dos nous fàrmacs, rimegepant i lasmiditan.
En canvi, per al tractament preventiu s’utilitzen propranolol, metoprolol, flunarizina, amitriptilina, topiramat, toxina botulínica A, a més d’altres fàrmacs amb evidència demostrada però sense indicació terapèutica com àcid valproic, candestartan, lisinopril i venlafaxina. En els últims anys s’han comercialitzat els anticossos monoclonals bloquejadors del pèptid relacionat amb el gen de la calcitonina (CGRP) o del seu receptor.

Assaig clínic aleatoritzat pragmàtic en el que es preten avaluar la efectivitat dels fàrmacs més freqüentment utilitzats com a primera línia en atenció primària com a tractament preventiu per la migranya segons la reducció de dies de migranya al mes (DMM), comparant amitriptilina, flunarizina i topiramat amb propanolol.

Els antagonistes de la vitamina K (AVK) i els anticoagulants orals directes (ACOD) poden interaccionar amb un gran nombre de fàrmacs per mecanismes farmacocinètics (FC) i/o farmacodinàmics (FD). Sovint, aquestes interaccions poden disminuir o augmentar l’efecte dels anticoagulants. En el cas d’un augment de l’efecte, poden acabar produint-se hemorràgies que poden arribar a ser greus i provocar l’ingrés hospitalari.
El nostre objectiu és analitzar quines hemorràgies de la nostra cohort de dades d’un estudi previ (2011-2020) poden haver estat ocasionades per interaccions FC i/o FD dels ACO amb altres tractaments concomitants. És per això que plantegem un estudi cas-control, on els casos seran tots els pacients que hagin patit alguna hemorràgia major durant el període d’estudi, per analitzar l’associació d’aquestes hemorràgies amb l’exposició concomitant d’ACO i altres fàrmacs que potencialment hi poden interaccionar.
Amb les dades que ja tenim disponibles (2011-2020) podem analitzar algunes de les interaccions dels ACO. Tanmateix, com que en aquella extracció no es van sol·licitar tots els fàrmacs que potencialment interaccionen amb ACO, es per això que necessitem afegir alguns grups farmacològics tant a prescripció com a facturació, i afegir la facturació d’alguns fàrmacs pels quals només havíem demanat prescripció.
Els fàrmacs que ja teníem a prescripció i ara necessitem facturació són:
• C01BD: Antiarítmics classe III (amiodarona, dronedarona)
• C08DA01: Verapamil
• C08DB01: Diltiazem
• C10AA: Estatines
• H02A, H02B: Corticoides sistèmics
• M01A: AINE
Els fàrmacs nous a afegir tant a prescripció com a facturació són:
• J01FA: Macròlids
• J01M: Quinolones
• J02AB, J02AC: Antifúngics
• L04AD01: Ciclosporina
• M04AA01: Al·lopurinol
• N02AX02, N02AJ13, N02AJ14: Tramadol
• N06A: Antidepressius

Rationale and background: Paxlovid consists of nirmatrelvir (formerly PF-07321332), a potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, co-administered with a low dose of ritonavir, which acts as a pharmacokinetic enhancer, orally twice a day for 5 days. Paxlovid is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19.
The safety of Paxlovid in pregnant women is not known. The post-authorisation safety study (PASS) of Paxlovid in pregnant women is a regulatory commitment to the European Medicines Agency (EMA) and the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA).
Research question and objectives: The primary study objective is to estimate the birth prevalence, prevalence ratio, and prevalence difference of the following adverse pregnancy, offspring, and maternal outcomes in women with COVID-19 who are exposed to Paxlovid during pregnancy compared with those in women with COVID-19 who are exposed to molnupiravir (or other comparable medications for COVID-19), where available, during pregnancy or to women with COVID-19 unexposed to any study medications during pregnancy:
Pregnancy outcomes
• Spontaneous abortion
• Elective termination
• Stillbirth
• Preterm delivery
Offspring outcomes
• Major congenital malformations
• Intrauterine growth retardation/small for gestational age
Maternal outcomes
• Gestational diabetes
• Gestational hypertension
• Postpartum haemorrhage
• Maternal death
The secondary study objective is to assess maternal exploratory outcomes in outpatient and inpatient settings as available that will be identified based on conditions appearing in the study population after exposure to Paxlovid.
Study design: The study will focus on pregnant women. Within this population, there will be a descriptive analysis and comparative analyses. Molnupiravir, an antiviral with a similar recommended usage, will be used as an active comparator in the data sources in which it is available; other drugs may be incorporated as active comparators as more information becomes available. At the time of preparing this protocol, molnupiravir was not utilised or its use was not captured by some of the data sources (eg, France and Information System for Research in Primary Care [SIDIAP] in Catalonia, Spain). Therefore, a second comparator group is included in the study: individuals with COVID-19 unexposed to any study medication. Other medications to treat COVID-19 will be considered as active comparators in the future.
The study period will start on 01 January 2022 (in alignment with regulatory authorisation and launch in Europe) and end as late as possible.
Population: The target study population will be individuals with COVID-19 exposed to Paxlovid or comparator drug molnupiravir or other comparable medications and individuals unexposed to Paxlovid, molnupiravir, or other comparable medications (the unexposed comparison group), while they are pregnant.
Data sources: As of 20 September 2022, the MAH has confirmed that Paxlovid has been supplied to France, Germany, Italy, Spain, Slovenia, Sweden, and the UK, initially or continuing under special government contracts, resulting in different distribution and reimbursement channels being used and subsequent challenges capturing its prescription and distribution. Current information is that prescribed/dispensed Paxlovid should be captured in existing electronic population data sources in France, Spain, and the UK. The Italian Medicines Agency (AIFA) established a national registry for Paxlovid and other antivirals to treat COVID-19. At the time of this writing, capture of Paxlovid dispensing/prescriptions in the existing electronic data sources commonly used for pharmacoepidemiological research in Italy at this moment is expected to be minimal. As long as the German government continues to cover payments for Paxlovid, it is expected that Paxlovid prescriptions will not be captured in the German Statutory Health Insurance data sources.
The proposed data sources are the French Administrative Healthcare Database (SNDS), SIDIAP (Catalonia, Spain), and Clinical Practice Research Datalink–Aurum (CPRD Aurum) (UK). The UK OpenSAFELY data source and the AIFA patient registry will continue to be explored as potential supplementary data sources for this study.
Study size: All individuals meeting eligibility criteria during the study observation period will be included. As the summaries of product characteristics (SmPCs) recommend against use in pregnancy, Paxlovid exposure in this population is anticipated to be small.
Data analysis: Study data will be analysed as a cohort. Descriptive baseline characteristics will include tabulations of age, sex, comorbidities, selected concurrent medications, COVID-19 vaccination status, history of COVID-19, current COVID-19 status and setting of Paxlovid use (among Paxlovid users). Comparative analyses will be based on the estimation of risk/prevalence, risk/prevalence ratios, and risk/prevalence differences. Comparative analyses will control for measured confounding within each data source. Aggregated results from each data source will be combined using meta-analytic techniques as numbers allow. If a study population is too small, analyses will be only descriptive; pooling of results from various data sources will be undertaken only if at least 3 independent data points are available.

Study to be conducted with the ConcePTION common data model. We plan to extract the data for both Paxlovid protocols (pregnancy & liver_renal populations) in a unique extraction (one in 2024 for interim report 1, another in 2025-26 for interim 2 and final report), but we present two different application forms for each protocol endorsed by PRAC (EMA).
Paxlovid is dispensed in a specific circuit in Spain, not in the usual electronic prescription.

Rationale and background: Paxlovid consists of nirmatrelvir (formerly PF-07321332), a potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, co-administered with a low dose of ritonavir, which acts as a pharmacokinetic enhancer, orally twice a day for 5 days. Paxlovid is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19.
The safety of Paxlovid in individuals with hepatic or renal impairment is not known. Assessing the safety of Paxlovid among individuals with moderate or severe hepatic or renal impairment is a regulatory commitment to the EMA.
Research question and objectives:
• What is the safety profile of Paxlovid in patients with COVID-19 and moderate or severe hepatic impairment?
• What is the safety profile of Paxlovid in patients with COVID-19 and moderate or severe renal impairment?
For the population of individuals with moderate or severe hepatic impairment, the objectives are:
Primary objectives
• To assess the safety of Paxlovid relative to the comparator populations prescribed molnupiravir (or other comparable medications for COVID-19), where available, and to unexposed patients with COVID-19.
• To assess side effects resulting from drug overexposure due to impaired liver function and with regard to severity and frequency compared with comparator groups. Safety outcomes for primary objectives are all safety events in outpatient and inpatient settings, as available, including the following safety outcomes of special interest:
• Hepatic transaminase elevations, clinical hepatitis, or jaundice
• Severe vomiting, nausea, diarrhoea, or abdominal pain
• Dysgeusia, headache, or hypertension
• Anaphylactic reactions
Secondary objective
• To assess all safety events included in the primary objective that require hospitalisation or emergency department visits
For the population of individuals with moderate or severe renal impairment, the objectives are:
Primary objectives
• To assess the safety of Paxlovid relative to the comparator population prescribed molnupiravir (or other comparable medications for COVID-19), where available, and to unexposed patients with COVID-19.
• To assess side effects resulting from drug overexposure due to impaired renal function and with regard to severity and frequency compared with comparator groups.
Safety outcomes for primary objectives are all safety events in outpatient and inpatient settings, as available, including the following safety outcomes of special interest:
• Severe vomiting, nausea, diarrhoea, or abdominal pain
• Dysgeusia, headache, or hypertension
• Anaphylactic reactions
Secondary objective
• To assess all safety events included in the primary objective that require hospitalisation or emergency department visits
Study design: The study will employ a cohort design and will make secondary use of multiple sources of data from electronic health records and/or claims data in European countries. Data sources currently selected have the ability to capture Paxlovid exposure where the target populations, study outcomes, and key covariates can be ascertained. The feasibility component of this research programme will provide counts of the target population, separately for Paxlovid users, users of molnupiravir, users of other comparable medications (Section 9.1.2, Table 2), and the unexposed comparator group. Relevant patient characteristics will be presented for each exposure group in the target population to allow an assessment of the feasibility of comparative analyses. Molnupiravir, an antiviral with a similar recommended usage, will be used as an active comparator in the data sources for which it is available; other drugs may be incorporated as active comparators as more information becomes available. At the time of preparing this protocol, molnupiravir was not utilised, or its use was not captured by some of the data sources (eg, France and Information System for Research in Primary Care [SIDIAP] in Catalonia, Spain). Therefore, a second comparator group is included in the study: individuals in the target populations with COVID-19 who had not received Paxlovid, molnupiravir or other comparable medications, referred to as “unexposed patients”. The study period will start on 01 January 2022 (in alignment with regulatory authorisation and launch in Europe) and end based on the calendar period coverage at the time of the last data extraction.
Population: The target study populations are individuals with moderate or severe hepatic or renal impairment with COVID-19 exposed to Paxlovid or comparator drug molnupiravir or other comparable medications, and individuals unexposed to Paxlovid, molnupiravir, or other comparable medications (the unexposed comparison group).
Data sources: As of 30 September 2022, the MAH has confirmed that Paxlovid has been supplied to France, Germany, Italy, Spain, Slovenia, Sweden, and the United Kingdom (UK), initially or continuing under special government contracts, resulting in different distribution and reimbursement channels being used and subsequent challenges capturing its prescription and distribution. Current information is that prescribed/dispensed Paxlovid should be captured in existing electronic population data sources in France, Spain, and the UK. The Italian Medicines Agency (AIFA) established a national registry for Paxlovid and other antivirals to treat COVID-19. At the time of this writing, capture of Paxlovid dispensing/prescriptions in the existing electronic data sources commonly used for pharmacoepidemiological research in Italy is expected to be minimal. As long as the German government continues to cover payments for Paxlovid, it is also expected that Paxlovid prescriptions will not be captured in the German Statutory Health Insurance data sources.
The proposed data sources for this study are the French Administrative Healthcare Database (SNDS), SIDIAP (Catalonia, Spain), and Clinical Practice Research Datalink Aurum (CPRD Aurum) (UK). The UK OpenSAFELY data source and the AIFA patient registry will continue to be explored as potential supplementary data sources for this study.
Study size: All individuals meeting eligibility criteria during the study observation period will be included. As the summaries of product characteristics (SmPCs) caution (EU) or contraindicate (UK) use in severe hepatic or renal impairment, Paxlovid exposure in these populations is anticipated to be small.
Data analysis: Study data will be analysed as a cohort. Descriptive baseline characteristics will include tabulations of age, sex, comorbidities, selected concurrent medications, COVID-19 vaccination status, history of COVID-19, current COVID-19 status and setting of Paxlovid use (among Paxlovid users). Comparative analyses will be based on the estimation of risk ratios and risk differences. Comparative analyses will control for measured confounding within each data source. Aggregated results from each data source will be combined using meta-analytic techniques as numbers allow. If a study population is too small, analyses will be only descriptive; pooling of results from various data sources will be undertaken only if at least 3 independent data points are available.

Study to be conducted with the ConcePTION common data model. We plan to extract the data for both Paxlovid protocols (pregnancy & liver_renal populations) in a unique extraction (one in 2024 for interim report 1, another in 2025-26 for interim 2 and final report), but we present two different application forms for each protocol endorsed by PRAC (EMA).
Paxlovid is dispensed in a specific circuit in Spain, not in the usual electronic prescription.

RIMEGEPANT (VYDURA®) HA ESTAT AUTORITZAT PER L’EMA, PERÒ A ESPANYA ENCARA NO DISPOSA DE DECISIÓ DE PREU NI FINANÇAMENT.
EL CHMP DE L’EMA VA APROVAR AQUEST PROTOCOL D’ESTUDI POST-AUTORITZACIÓ AMB ELS “TIMELINES” INDICATS AL PROTOCOL, DE MANERA QUE ENTRE EL 2on I 3er TRIMESTRE DE 2024 HEM D’ENTREGAR EL CORRESPONENT “PROGRESS REPORT.
COM QUÈ EL FÀRMAC ENCARA NO TÉ PREU NI FINANÇAMENT, PER TANT, NO ES POSSIBLE PRESCRIURE’L, EVIDENTMENT NO HI HAURÀ USUARIS DEL FÀRMAC EN EL MOMENT D’ENTREGAR EL “PROGRESS REPORT”, I NO S’HAN D’EXTRAURE DADES DE SIDIAP FINS A 2025, PERÒ PER COMPLIR AMB ELS “TIMELINES” I PODER ENTREGAR AQUEST “PROGRESS REPORT”, EL PROTOCOL D’ESTUDI HA D’ESTAR APROVAT ABANS PEL COMITÉ CIENTÍFIC DE SIDIAP I PEL CEIm.

Rationale and background: Rimegepant is a calcitonin gene–related peptide (CGRP) receptor antagonist for the treatment of acute migraine and preventive treatment of episodic migraine. The European Medicines Agency (EMA) granted approval for rimegepant in the European Union (EU) in Apr-2022 both for the acute treatment of migraine with or without aura in adults and for the preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month.
The opinion of the Committee for Medicinal Products for Human Use (CHMP) in the Day 180 review was that “Patients with cardiovascular diseases should be included as missing information. The applicant should further elaborate on this matter, taking into account the inclusion and exclusion criteria applied in the clinical trials…setting depending on the indication, and if a (theoretical) cardiac risk for Vydura exists.”
As part of the risk management plan for rimegepant in Europe, Biohaven is committed to address the request from the EMA and the Medicines and Healthcare Products Regulatory Agency (MHRA) to conduct a post-authorisation safety study (PASS) to evaluate whether there is an increased risk of major adverse cardiovascular events (MACE) among patients with migraine and history of cardiovascular disease (CVD) initiating treatment with rimegepant compared with that among patients with migraine, with history of CVD, and being treated with other treatments for migraine, either continuing the current treatment or initiating a new one, other than rimegepant. The study will also describe the use of rimegepant in the initial years after approval in the same population.

Research question and objectives: The research question is as follows: does the use of rimegepant increase the risk of MACE compared with other treatments for migraine in patients with migraine and history of CVD?
The study has 2 primary objectives:
1. To evaluate whether treatment initiation with rimegepant versus treatment with other preventive treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with preventive migraine therapies
2. To evaluate whether treatment initiation with rimegepant versus treatment with other acute treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with acute migraine therapies
The study has 1 secondary objective: To describe the patient characteristics of rimegepant initiators with migraine and a history of CVD (including demographics, comorbidities, comedications, and health care utilisation) at the time of rimegepant initiation and to describe their patterns of rimegepant use, including acute, preventive, or both.

Study design: This is a non-interventional population-based prospective cohort study using a prevalent new-user design. The study will be conducted in multiple data sources, comparing patients with treated migraine and a history of CVD who initiate rimegepant to comparator groups of similar patients with migraine and a history of CVD from the same data source. Both the rimegepant and comparator groups will consist of patients who have been treated with other preventive or acute treatment. This study will estimate the cumulative incidence of study outcomes with corresponding 95% confidence intervals (CIs) comparing the rimegepant initiators to the appropriate comparator group (one group of continuators or initiators of a preventive migraine medication and another group of continuators or initiators of an acute migraine medication). The analysis will be conducted separately in each data source, and overall estimates of effect will be obtained using appropriate statistical techniques. Confounding will be addressed primarily by propensity score weighting.

Population: The study population will comprise adults with migraine and history of CVD registered in each electronic health care data source who are on treatment with a qualifying acute or preventive migraine medication during the study period.
To be eligible for inclusion into the study populations, patients must have a prescription/dispensing of rimegepant or a comparator treatment for migraine within the study period, be adults (aged 18 years or older) at the index date, have at least 12 months of data available before the index date, have a diagnosis of migraine any time before or on the index date, and have a CVD diagnosis any time before or on the index date. The index date in the rimegepant groups will be defined as the date in which a patient receives a first prescription/dispensing of rimegepant within the study period and meets all the eligibility criteria. Potential index dates for the comparator groups will be defined as the date on which a patient receives a prescription/dispensing of a qualifying migraine study drug within the study period and meets all the eligibility criteria. In the analysis phase, exposure sets will be created based on the time since first prescription/dispensing of migraine medication identified in the database any time before the index date. The index date for the comparator groups will be the date of the included comparator prescriptions/dispensings within exposure sets including rimegepant index dates.
Because patients may be used as comparators for multiple rimegepant patients, a single comparator patient may have multiple comparator index dates. Furthermore, rimegepant patients may be used as comparators before their initial rimegepant prescription/dispensing.

Data sources: The study will be implemented in 4 health care data sources:
– Danish National Health Registers (DNHR) (Denmark)
– PHARMO Database Network (the Netherlands)
– Information System for the Development of Research in Primary Care (SIDIAP) (Spain)
– Clinical Practice Research Datalink (CPRD) (United Kingdom [UK])

Study size: Considering a scenario of an IR of MACE ranging between 176.1 and 210.9 per 10,000 patients and having a cohort of patients with > 1 to 5 years after migraine diagnosis, a sample size of 2,500 patients in the rimegepant group would result in a 86% or higher probability that the upper bound of the observed RR would be below 1.8.

Data analysis: Each research partner will conduct analyses separately within each data source, and results will be pooled via meta-analytic methods, if appropriate, at the end of the study. The analysis will comprise 4 different steps: select the study population, assign exposure and define follow-up, describe the study cohorts and patterns of rimegepant use, and estimate exposure propensity scores. Stabilised propensity score weights will be used in the comparative analyses, where the inverse of the propensity score is multiplied by the probability of receiving the treatment independently of baseline covariates. Crude and adjusted incidence rates of MACE with their 95% CIs will be estimated using a Poisson regression model with robust estimation of variance. Cumulative incidence of MACE will be estimated using the Kaplan-Meier estimator for each of the 4 exposure groups. Finally, for each comparison, crude and adjusted RRs and risk differences at various times during follow-up (3, 6, 9, and 12 months) will be estimated using the Kaplan-Meier estimator, and 95% CIs will be derived using bootstrap methods. Adjusted hazard ratios (HRs) will be estimated with a Cox model.

Objectius: Les infeccions del tracte urinari (ITU) representen la segona patologia infecciosa més freqüent en atenció primària. El seu maneig ha estat el motiu de molts estudis, però fins a la data no s’ha avaluat la idoneïtat del seu maneig a la totalitat de l’àrea de Catalunya.
Aquest projecte està compost de quatre subprojectes: 1) Conèixer l’epidemiologia dels diferents tipus d’ITU i el seu maneig terapèutic i demanda d’urocultius; 2) Avaluar la correlació de consum total i tipus d’antibiòtics per a ITUs de repetició amb la presència i gravetat de complicacions infeccioses d’origen urològic, especialment pielonefritis i sepsis, i dues infeccions potencialment greus: pneumònia i COVID-19; 3) Crear una escala predictora associada al diagnòstic d’ITU que es complica en una pielonefritis aguda; i 4) Conèixer el grau d'(in)adequació en la sol·licitud d’urocultius en base a les guies de pràctica clínica.
Metodologia: Per als dos primers estudis es durà a terme un estudi observacional descriptiu amb població de 18 anys o més que tingui almenys un diagnòstic de qualsevol forma d’ITU durant el decenni de estudi, des del 2012 al 2021. En el tercer estudi, es revisaran les dades de les històries clíniques d’aquells pacients amb hospitalització per pielonefritis entre 2017 i 2021.
En els tres primers estudis, les dades seran obtingudes de la base de dades SIDIAP (Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària), la qual conté informació clínica anonimitzada d’un 80% aproximadament de la població de Catalunya completant la informació mitjançant les dades del Conjunt Mínim Bàsic de Dades (CMBD) d’altes hospitalàries (CMBD-AH). En el primer estudi s’avaluarà el maneig dels diferents tipus d’ITUs en dones i homes, tractaments administrats i durada, teràpies supressores en les ITUs de repetició i sol·licitud d’urocultius. En el segon estudi es seguiran dones amb ITUs de repetició tractades amb teràpies supressores vs. dones amb ITUs de repetició sense teràpies supressores i resta de dones amb ITUs tractades puntualment i es valorarà la presència de pielonefritis aguda, sepsis, pneumònia i COVID-19 i es construirà una variable de gravetat que inclourà mortalitat i hospitalització. En el tercer estudi es farà un estudi retrospectiu a partir dels diagnòstics de pielonefritis aguda des del 2017 fins al 2021 en ambdós sexes i s’avaluaran els criteris de gravetat associats a les ITUs que aquests pacients han presentat anteriorment. En el quart estudi es durà a terme un estudi retrospectiu de totes les sol·licituds d’urocultius rebudes al Servei de Microbiologia de l’Hospital Joan XXIII de Tarragona en el 2021 i es farà un mostreig en centres d’atenció primària de la Gerència Tarragona-Reus, avaluant els motius de sol·licitud.
Resultats esperats: D’acord amb la literatura publicada d’estudis locals esperem trobar un alt grau d’inadequació del maneig diagnòstic i terapèutic de les ITUs Catalunya, principalment en les ITUs no complicades, especialment en determinats subgrups de pacients, com poden ser dones amb patologies prèvies, comorbiditats associades i homes. Cal també esperar una inadequació en l’ús de teràpies supressores, malgrat les guies les recomanen amb dues o més ITUs en els darrers 6 mesos o tres o més en el darrer any. Probablement observarem una alta inadequació en la sol·licitud d’urocultius, amb una excessiva sol·licitud en ITUs no complicades, bacteriúries asimptomàtiques i seguiments i, per contra, una infrasol·licitud d’urocultius en ITUs complicades. Esperem crear una escala predictora que ajudi als clínics identificar les situacions en què les ITUs poden complicar-se en pielonefritis. També esperem trobar que un ús de teràpies llargues, moltes pautes prèvies i un ús d’antibiòtics d’ampli espectre en dones s’associen a una major probabilitat de presentar complicacions infeccioses, com pneumònia i COVID-19 i major gravetat d’aquestes.

El uso de fármacos en el embarazo y la lactancia es una circunstancia frecuente para el control
de patologías crónicas o tratar problemas médicos agudos.
A pesar de ello, la información sobre seguridad, efectividad y manejo de medicamentos en esta
población no está disponible de forma rutinaria, debido a los problemas éticos que comporta la
participación de mujeres gestantes y lactantes en ensayos clínicos y la dificultad de equilibrar
beneficios y riesgos para ellas y su descendencia en la exposición a medicamentos.
Actualmente, gracias a los programas de prevención de embarazos establecidos por las agencias
reguladoras para fármacos con efecto teratógeno y a los sistemas de monitorización de defectos
congénitos e identificación de teratógenos, es difícil imaginar una nueva epidemia como la de la
talidomida. Sin embargo, en la práctica asistencial los proveedores de salud continúan teniendo
dificultades para interpretar y evaluar beneficios y riesgos de gran número de fármacos, y
realizar la posterior decisión compartida con las mujeres embarazadas y lactantes que precisan
tomar medicación.
Para mejorar la interpretación de los datos, en 2015 la Food and Drug Administration (FDA)
implantó un nuevo modelo para categorizar los fármacos en el embarazo, Pregnancy and lactation
labelling rule (PLLR), con el objetivo de ayudar en la toma de decisiones en la prescripción,
que incluye un narrativo que describe riesgos y consideraciones clínicas en 3 apartados:
gestación y parto, lactancia y potencial reproductivo en hombres y mujeres. Es un modelo más
similar a la normativa europea, donde encontramos información en la ficha técnica del producto.
Además, la European Medicines Agency (EMA) establece en su Guía de Buena Práctica en
Farmacovigilancia para poblaciones específicas; mujeres embarazadas y lactantes, que es
necesario realizar estudios observacionales post autorización de seguridad en los fármacos que
no puedan ser discontinuados durante el embarazo, fármacos para tratar enfermedades propias de
la gestación/lactancia o los que en estudios preclínicos han mostrado algún tipo de riesgo para
la descendencia.
En los últimos años el uso de bases de datos ha permitido realizar estudios
farmacoepidemiológicos relacionados con el uso de fármacos durante embarazo y lactancia,
permitiendo conocer la exposición a fármacos durante estos periodos y, mediante la vinculación
madre-descendencia, estudiar problemas de salud de la descendencia, así como información sobre
posibles confusores.
La evaluación del uso de fármacos durante el embarazo y la lactancia no se ha evaluado en
nuestro ámbito mediante este tipo de estudios. Nuestro objetivo es evaluar el uso de fármacos
durante embarazo y lactancia mediante un estudio de cohortes de base poblacional con datos de
SIDIAP (Sistema de Información para el Desarrollo de la Investigación en Atención Primaria), que
incluya mujeres embarazadas y lactantes, así como detectar posibles alteraciones congénitas y
otros problemas de salud en el nacimiento y la infancia que puedan ser causados por la
exposición a fármacos de las madres durante el embarazo y la lactancia, lo cual permitirá
generar nuevas hipótesis de causalidad para futuros estudios que permitan corroborarlas o
rechazarlas.
También pretendemos explorar las creencias, experiencias y actitudes sobre el uso de fármacos en
embarazo y lactancia desde la perspectiva de las mujeres y sus parejas y de los profesionales de
la salud que las atienden mediante un estudio cualitativo exploratorio y un estudio
observacional descriptivo mediante la realización de encuestas, para detectar si existen falsas
creencias sobre el riesgo o la seguridad de los medicamentos.
Así podremos aportar información que permita mejorar la evaluación del balance beneficio-riesgo
de los tratamientos farmacológicos antes de su prescripción a mujeres embarazadas o lactantes y
dar soporte a los clínicos en su labor durante el tratamiento y seguimiento de sus pacientes.

Antecedents: Des de la comercialització dels inicialment anomenats com a nous anticoagulants orals i actualment coneguts com anticoagulants orals directes (ACOD), ha disminuït l’ús dels fàrmacs antagonistes de la vitamina K (AVK) acenocumarol i warfarina.
La seva fàcil posologia i els aparents millors resultats en seguretat han fet dels ACOD una alternativa realment interessant per a pacients amb necessitats d’un tractament anticoagulant, p.ex pacients amb una fibril·lació auricular no valvular (FANV). Els ACOD no estan exempts de risc d’hemorràgia, però també han aparegut altres problemes de seguretat envers el potencial d’interacció amb altres medicacions freqüentment prescrites a pacients anticoagulats. Tant des de la perspectiva farmacocinètica com des de la farmacodinàmica els ACOD poden interaccionar amb altres medicacions disminuint la seva efectivitat (risc trombòtic) o incrementant el risc d’hemorràgia.
Hipòtesis: Les interaccions farmacològiques amb els ACOD resulten en un augment del risc d’efectes adversos, tant del risc d’hemorràgia com del risc d’esdeveniments trombòtics per una disminució de la seva efectivitat.
Objectius: Quantificar el risc de les interaccions farmacològiques (farmacocinètiques o farmacodinàmiques) més rellevants dels ACOD actualment comercialitzats a Catalunya i la seva repercussió clínica en forma d’esdeveniments hemorràgics o trombòtics durant 2014-2021.
Metodologia: Estudi observacional analític amb disseny autocontrolat. Formaran part de la cohort aquells individus que presentin un diagnòstic de FANV amb almenys 3 mesos d’exposició a un ACOD (dabigatran, rivaroxaban, apixaban, edoxaban). Els individus que entrin a la cohort s’analitzaran en base a la resta de medicacions que consumeixen amb especial èmfasi en fàrmacs que poden alterar el metabolisme dels ACOD a través del citocrom P-450 (ritonavir, rifampicina i dexametasona entre altres) o que per les seves característiques farmacodinàmiques puguin augmentar el risc d’hemorràgia (AINEs, ISRS, corticoides o antiagregants entre altres grups) o disminuir-lo (inhibidors de la bomba de protons). S’analitzarà el risc d’esdeveniments hemorràgics o trombòtics que impliquin l’ingrés a un centre hospitalari amb una alta d’hemorràgia rellevant, hemorràgia gastrointestinal, hemorràgia intracranial, ictus o embòlia sistèmica.
Dades: dades de prescripció, dispensació i facturació farmacèutica d’ACOD i els grups d’interès per la seva capacitat d’interacció (Sistema Integrat de Recepta Electrònica o SIRE i el Registre de Pacients i Tractaments o RPT que conté la Facturació de Medicaments Hospitalaris de Dispensació Ambulatoria o MHDA) amb data i posologia. Dades del CMBD-HA.

Antecedentes. Existe escasa evidencia sobre las experiencias en relación al uso de fármacos, medicina complementaria y alternativa y vacunación durante el embarazo y la lactancia, siendo la investigación necesaria para minimizar los potenciales riesgos para mujeres, otras personas con capacidad de gestar y lactar e hijas/os. Objetivos. El objetivo principal de este estudio consiste en explorar las experiencias, creencias y actitudes sobre el uso de fármacos, los productos de la medicina complementaria y vacunas durante el embarazo y el periodo de lactancia, tanto de las mujeres y otras personas con capacidad gestar y lactar (con o sin patología crónica), como de sus parejas, así como de los profesionales de la salud, en el área de Cataluña. Metodología. Se trata de un estudio cualitativo con una aproximación socioconstruccionista y con perspectiva de género, investigando las experiencias en tres grupos de participantes: 1) mujeres y personas embarazadas y lactantes, 2) parejas en estas etapas y 3) profesionales de la salud. El reclutamiento será intencional, razonado y de tipo teórico. El estudio se llevará a cabo entre enero 2023 y abril 2024, mediante entrevistas individuales y grupos de discusión, en servicios de atención primaria y hospitalaria en el área de Cataluña. Análisis de datos. Se usará el análisis temático para el análisis de datos. También, se seguirán los criterios de Lucy Yardley, así como el uso del Critical Appraisal Skills Programme para asegurar rigor y calidad a la investigación. Aplicabilidad y relevancia. Esperamos que visibilizar las experiencias de las mujeres y personas embarazadas y lactantes, sus parejas y profesionales sanitarios en el uso de fármacos, medicina alternativa y vacunación, tenga un impacto en la gestión de la atención sanitaria, social y educativa, haciendo énfasis en el bienestar y la salud de las mujeres y otras personas con capacidad de gestar y lactar y sus hijas/os.

Tots els nous hipoglucemiants no insulínics (HNI) han demostrat eficàcia en la reducció de l’HbA1c (major o menor efecte glucèmic segons el grup farmacològic) i han demostrat no associar-se a pitjors resultats de morbimortalitat CV en els estudis de seguretat CV requerits per les agències reguladores. Tot i que alguns d’aquests estudis amb ISGLT2 i ARGLP1 suggereixen que aquests fàrmacs podrien tenir beneficis en morbimortalitat CV, fins ara no està clarament establert quin és l’impacte clínic real que tenen en el tractament de la DM2 en la pràctica clínica del nostre entorn. No hi ha estudis poblacionals en el nostre entorn que hagin analitzat l’associació entre la introducció dels nous grups d’ISGLT2 i ARGLP1 i els esdeveniments clínics.
Objectiu general: estudiar l’associació entre l’evolució de la utilització dels diferents hipoglucemiants i l’evolució dels resultats en salut en la població de pacients amb DM2 de Catalunya en el període 2015-2020.
Es tracta d’un estudi observacional de disseny ecològic. A més, es durà a terme una anàlisis descriptiva dels resultats en salut en els diferents anys segons el tipus de tractament hipoglucemiant. Totes les dades provenen de fonts secundàries: fitxer de prestacions farmacèutiques del CatSalut, SIDIAP, CMBDs, RCA.
Els objectius a analitzar amb dades de SIDIAP són:
– Descriure l’evolució en el percentatge de pacients controlats (HbA1c < 7%) i de les HbA1c mitjanes en el període 2015-2020 en la població de pacients amb DM2 (amb tractament o sense) i en la població de pacients amb DM2 tractats amb hipoglucemiants. - Descriure l'evolució en el percentatge de pacients controlats (HbA1c < 7%) i de les HbA1c mitjanes en el període 2015-2020 en la població de pacients amb DM2 tractats amb hipoglucemiants en funció del tipus de tractament: HNI en monoteràpia, combinacions d'HNI, insulina en monoteràpia i combinacions d'HNI amb insulina. - Descriure l'evolució en el percentatge de pacients amb obesitat (índex de massa corporal [IMC] ? 30 Kg/m2) i de les mitjanes d'IMC en el període 2015-2020 en la població de pacients amb DM2 (amb tractament o sense) i en la població de pacients amb DM2 tractats amb hipoglucemiants. Paraules clau: diabetis mellitus tipus 2, hipoglucemiants no insulínics, evolució, mortalitat, esdeveniments cardiovasculars, HbA1c.

Rationale and background: The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of coronavirus disease 2019 (COVID-19), has led to a global pandemic. AZD1222 is a vaccine developed to prevent COVID-19. Now known as COVID-19 Vaccine AstraZeneca, the vaccine has received emergency use authorisation in the United Kingdom (UK) and conditional approval by the European Commission. Several important potential risks have been identified based on the experience of other non-COVID-19 vaccines. The clinical development programme also had limited enrolment of certain patient populations, including pregnant or breastfeeding women, individuals who are immunocompromised, frail persons with comorbidities, those with autoimmune or inflammatory disorders, and use with other vaccines such as an influenza vaccine.
Research question and objectives: What are the incidence rates (IRs) of safety events of interest (based on adverse events of special interest [AESIs]) among individuals vaccinated with AZD1222 and in individuals who have not received any vaccination for COVID-19, overall and in subpopulations of interest, within selected European data sources? How do the IRs compare with one another? What are the baseline characteristics of individuals who received at least one dose of AZD1222? How many of them received a second dose of a COVID-19 vaccine, which vaccine did they receive, and when did they receive it?
Study design: A multi-country, retrospective cohort design will be used to estimate the incidence of AESIs after receiving AZD1222 and will compare this incidence with that occurring in an unvaccinated comparator group. Where appropriate, the study will also use a self-controlled risk interval (SCRI) design. The study period will start on 04 January 2021, when the vaccine was first used in the UK, and will end approximately 24 months after it is introduced in the last country among participating data sources.
Population: The source population will comprise all individuals registered in each of the health care data sources. An exposed cohort will be identified based on first vaccination with AZD1222 (index date). A concurrent comparator population will be identified among subjects who have not received any vaccination for COVID-19 matched on the vaccinee’s index date, age, and gender.
Variables: Receipt of AZD1222, other SARS-CoV-2 vaccines, and dates of vaccination will be obtained from all possible sources that capture COVID-19 vaccination, such as pharmacy dispensing records, general practice records, and immunisation registers. Safety outcomes include safety concerns and other AESIs. These outcomes will be identified using algorithms based on codes for diagnoses, procedures, and treatments in electronic data, and they will be defined uniformly across the data sources to the fullest extent possible. Operational case definitions from the ACCESS (vACcine Covid-19 monitoring readinESS) project will be implemented for the AESIs for which they have been developed.

Desarrollo de algoritmos parobabilísticos para estimación de tratamientos combinados en registros electrónicos de salud.

El algoritmo usa datos de fármacos, prescripciones principalmente, y nos permitirá detectar de forma automática cuando se observan tratamientos combinados, su duración, posibles cambios y discontinuaciones.

Para poder publicar el método, se ha diseñado un ensayo de validación que requiere de datos reales, en este caso los datos de la extracción de SIDIAP del proyecto titulado ‘Características sociodemográficas, clínicas y farmacológicas asociadas con el pronostico en pacientes con infección por SARS-CoV-2 (4R20/029, SIDIAP 396)’

Background: Edoxaban is an oral anticoagulant approved in 2015 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). A European non-interventional prospective post-approval safety study (ETNA-AF study – EU-PAS register numbers EUPAS8896) is ongoing to gain insight into the safety and efficacy of edoxaban in non-preselected patients with non-valvular atrial fibrillation (NVAF) treated with edoxaban.
Objectives: The main objective of this study is to put in perspective the results of the ETNA-AF study using secondary electronic health care data and administrative health data of patients with NVAF treated with edoxaban and thus, gain additional insight into the effectiveness and safety of edoxaban in real world setting.
Methods: In this multi-country retrospective longitudinal cohort study, adult patients with NVAF initiating edoxaban will be identified in five large European databases: LHU data (Italy), GePaRD database (Germany), SIDIAP (Spain), PHARMO data (Netherlands), UK CPRD AURUM linked to HES data (UK). Observational period will be the same as in the ETNA-AF study, that is, up to 48 months after initiation of edoxaban. Primary outcomes will be occurrence of bleeding events, drug-related adverse events and mortality (all-cause, CV-related) during the observational period.
Analysis: Analysis will be purely descriptive. Baseline characteristics, primary and secondary outcomes will be analyzed for each individual database and overall, across all databases, using standard descriptive statistics. The risk of occurrence of events of interest during the observational period will be characterized using a Kaplan-Meier analysis. Country-specific results will be combined in a meta-analysis.

Justificación: Múltiples estudios han identificado factores relacionados con la evolución de la enfermedad COVID-19 desde su inicio en China. Actualmente España está entre los países con mayor número de infectados y muertos, lo que está generando datos útiles para su análisis y el futuro manejo de la enfermedad.
Objetivo: evaluar la asociación de factores sociodemográficos, clínicos y farmacológicos con la tasa de infección, la gravedad y el desenlace fatal del COVID-19.
Metodología: estudio observacional de cohortes de base poblacional en Cataluña. Análisis de variables sociodemográficas, comorbilidades y tratamientos para identificar factores de riesgo para la infección, mediante registro diagnóstico o PCR positiva para SARS-CoV-2, y su evolución (neumonía, ingreso, respiración asistida y muerte).

La incontinència urinària (IU) és la pèrdua involuntària d’orina i pot ser d’esforç (IUE), d’urgència (IUU) o mixta (IUM). Aquest estudi té com a objectius:
– Descriure la població que inicia tractament amb antiespasmòdics urinaris (anticolinèrgics urinaris o mirabegró): característiques sociodemogràfiques, comorbiditats, comedicacions, diferències per sexe i edat.
– Descriure l’ús d’absorbents d’orina per al tractament de la IU: número de pacients que utilitzen bolquers i reben tractament farmacològic simultàniament.
– Descriure principi actiu, dosi i durada dels tractaments farmacològics de la IU.
– Analitzar canvis de tractament i combinacions de principis actius.
– Estimar l’adherència al tractament farmacològic.
– Estimar la càrrega anticolinèrgica en aquells pacients tractats amb fàrmacs antimuscarínics i mirabegró.
La població d’estudi estarà formada per aquells pacients amb una nova prescripció de fàrmacs antiespasmòdics urinaris durant el període 2015-2017 i amb seguiment fins a 31/12/2018.

RATIONALE AND BACKGROUND
Irritable bowel syndrome (IBS) is a chronic, relapsing gastrointestinal condition characterised by abdominal pain, bloating, and changes in bowel habits. Prevalence estimations vary with the diagnostic criteria used, and in the United Kingdom (UK) were estimated between 9.5% and 22%. IBS can be classified according to Rome III criteria on the basis of the stool?s characteristics: IBS predominantly with diarrhoea (IBS-D); IBS predominantly with constipation (IBS-C); and IBS with mixed bowel habits (IBS-M). Approximately one-third of IBS patients have each type of the disease.
The commercialisation of linaclotide (Constella®), a guanylate cyclase-C receptor agonist with visceral analgesic and secretory activities, was approved as the first medicine authorised for the symptomatic treatment of moderate-to-severe IBS-C in adults in the European Union (EU).
Therefore, this study is planned to assess the safety of linaclotide in terms of the risk of severe complications of diarrhoea (SCD) during treatment and other risk factors among patients with IBS-C in Spain.
RESEARCH QUESTION AND OBJECTIVES
This study will occur over two phases. In Phase I, we will validate an algorithm for identifying SCD. In Phase II, we will use either a cohort design (Phase IIa) or a case-control design (Phase IIb) depending on the results the validation study to investigate whether use of linaclotide is associated with an increased risk of SCD.
The specific objectives of the study are:
Phase I: Validation Study
– Estimate the incidence of diarrhoea and identify patients experiencing severe complications of diarrhoea (SCD) among patients with IBS-C
– Validate a proposed diagnostic algorithm for SCD among patients with IBS-C
Phase IIa: Cohort Study
If a PPV>95% is achieved in the validation study, then we will use a cohort design to:
– Estimate the incidence of SCD among IBS-C patients prescribed linaclotide overall and stratified by groups of interest (i.e. patients ?65 years, patients with hypertension, diabetes, or cardiovascular disease diagnostic codes)
– Identify risk factors for SCD, with linaclotide and laxative use being the key exposures of interest
Phase IIb: Case-control Study
If a PPV<95% is achieved in the validation study, then Phase IIb will be executed, in which a matched case-control design will be used to: - Identify risk factors for SCD, with linaclotide and laxative use being the key exposures of interest The rationale for this study design is that if the results from the validation study show that the SCD algorithm has a good performance, we can implement this algorithm to identify our outcome of interest within the entire study population and conduct a classic cohort analysis. However, if the algorithm has poor performance, then we will only be able to utilise confidently the data within the validation sample for the implementation of a matched case-control study. STUDY DESIGN The final decision on study design will be made following the validation stage. If the PPV is >95% then a cohort study design will be used, otherwise a matched case-control study will be used.
POPULATION
This study will use observational data from and Spain. The study population will be a cohort of IBS-C patients. Patients with less than 12 months of computerised records prior to IBS-C cohort entry date or no follow-up time will not be included.
VARIABLES
Users will be classified as current, never and past users. For Phase IIa (cohort study), these exposures will be defined based on drug prescriptions in a time-updated manner The outcomes of interest are severe complications of diarrhoea including dehydration that requires intravenous rehydration, dehydration that requires oral rehydration with solutions of electrolytes, electrolyte imbalance (potassium and sodium), oliguria, anuria, new onset-thromboembolism, new-onset orthostatic hypotension, new-onset syncope, new-onset dizziness, new-onset vertigo, acute renal failure, hypovolemic shock, hospitalisation due to diarrhoea, stupor, coma, or death.
All variables will be identified using diagnostic and procedure codes from general practitioner (GP) electronic medical records. IBS type and safety outcomes will be validated through a questionnaire to physicians treating the cases and controls included in the study.
DATA SOURCES
This part of the study will utilise data from the Information System for the Development of Research in Primary Care (SIDIAP). SIDIAP is a primary care database that collects longitudinal data from electronic medical records (EMRs) from 274 primary care centres in Catalonia since 2006, representing approximately 12% of the Spanish population. Data from primary care, specialised care, hospitals, and pharmacies are available, as well as patient characteristics like gender and date of birth, GP-diagnosed conditions, GP prescriptions, prescription dosing and size, date of prescription and dispensation, laboratory test results, other procedures, specialist referrals and diagnosis, hospital referrals, hospital procedures and discharge diagnosis, death date, and pregnancy information. GP diagnoses are coded following the ICD-10 codes, and hospital admissions are classified following the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision (ICD-9). Since 2018, SIDIAP no longer allows the possibility to contact physicians for extracting extended additional information on the patient through long questionnaires. However, there is the possibility of a text review of the primary care records. This text review can be used to validate cases of interest and it would be conducted by IDIAP?s clinical researchers. For this study, it is recommended by the data custodians that a review of free-text in the patient?s medical records is conducted to improve the validity of the actual study, in place of the previously planned validation strategy using questionnaires to GPs. This free-text review will be made after an anonymisation process of the clinical records and a natural language processing of the text.
STUDY SIZE
From the linaclotide drug utilisation study we know that the total number of linaclotide users in SIDIAP between 2014 and 2017 was 1,854 patients.
Within the IBS-C cohort, we expect to accrue a non-trivial number of cases (e.g., 94 cases of SCD with an incidence of 0.05% among IBS-C patients) and the same number (or larger) of controls (e.g., that would provide 80% power [or greater] to detect an OR=4 [or larger] associating SCD with a risk factor present in 5% of controls [notice that we expect exposure to linaclotide in approximately 5% of the cohort]).
DATA ANALYSES
Patient characteristics at cohort entry date will be described for the full cohort of patients with IBS-C, as well as incidence rate of diarrhoea.
If the results of the validation of cases and controls are satisfactory (positive predictive value of EMRs in Spain ? 95% and negative predictive value ? 99%), then information from the whole cohort will be used to estimate incidence rates for those groups of patients with IBS-C prescribed linaclotide and those who are potentially at increased risk of SCD and prescribed linaclotide. The crude incidence of diarrhoea and of severe complications of diarrhoea will be described by calculating the proportion of patients with IBS-C experiencing diarrhoea and SCD, respectively, and their associated 95% confidence intervals (CIs). Crude incidence rates of SCD will be also calculated.
Additionally, the hazard ratios of SCD and the exposures of interest (mainly prescription of linaclotide) will be estimated using Cox proportional hazard models.
If the results of the validation of cases and controls in Spain are not satisfactory (positive predictive value of our outcome algorithm in Spain < 95% or negative predictive value < 99%), only the nested case-control study will be performed and ORs of SCD and the same exposures of interest will be estimated using data from cases and matched controls by applying conditional logistic regression analysis. The goal is to assess SCD among patients who were treated with linaclotide, were ?65 years old, and had history of hypertension, diabetes or cardiovascular disease diagnostic codes (i.e., SCD occurrence is the outcome variable [yes/no] and the independent variables of main interest are whether the patient has a prescription for linaclotide, a prescription for laxatives, the patient is ?65 years old, and the patient has hypertension, diabetes, or cardiovascular disease diagnostic codes, all of them at index date, or not, controlling for potential confounders). Statistical analyses will be conducted using R statistical software.

RATIONALE AND BACKGROUND:
Retinoic acid analogues comprise of a group of active substances known as the retinoids and are available as topical and oral preparations. Therapeutic indications include the treatment of severe acne (such as nodular or conglobate acne) resistant to adequate courses of standard therapy, hand eczema resistant to empirical treatment measures, and severe forms of psoriasis and other skin conditions.
Therapy with systemic retinoids is associated with teratogenicity. Therefore, women who are pregnant or are planning a pregnancy must not be prescribed retinoids. Strict prescription guidelines and a PPP comprising education material for patients, physicians, and pharmacists as well as strict prescription guidelines have been put in place but exposure during pregnancy still occurs. In January 2016, a Pharmacovigilance Risk Assessment Committee (PRAC) review noted that there are concerns about how well the requirements of the PPP are followed in clinical practice. In July 2016, the PRAC initiated an article 31 referral to assess the effectiveness of risk minimisation in relation to the PPP. After completion of the review in March 2018, the European Medicines Agency (EMA) confirmed that an update of measures of the PPP for the oral retinoids acitretin, alitretinoin and isotretinoin is needed. They, therefore, mandated the conduct of a DUS (category 1) to assess the effectiveness of these updated risk minimisation measures (RMMs). In June 2018, the decision to strengthen the recommendations for pregnancy prevention for oral retinoids was issued by the European Commission (EC).
RESERACH QUESTION AND OBJECTIVES:
The aim of the Drug Utilizacion Study (DUS) is to address the following research question:
Is there a difference in physicians’ prescribing and monitoring practice in the periods before and after the update of the pregnancy prevention programme (PPP) for the oral retinoids acitretin, alitretinoin, and isotretinoin when treating women of childbearing potential?
PRIMARY OBJECTIVE:
To evaluate the changes in the prescribing and monitoring practices following the update of the PPP in females of childbearing potential receiving prescriptions of the oral retinoids acitretin, alitretinoin, or isotretinoin by comparing the following key elements of the PPP between the pre- and the postimplementation period:
? Contraceptives* before, during, and after treatment with oral retinoids
? Time interval between prescription dates for oral retinoids during treatment episode
? Laboratory pregnancy tests ? where available – before, during, and after treatment with oral retinoids
* contraceptive methods that require prescription and which are, therefore, captured in the administrative databases
SECONDARY OBJECTIVES:
? To describe the patient profile during the pre-and the post-implementation period, with respect to:
o Patient age
o Indication for oral retinoids
? To describe the prescriber specialty during the pre-and the post-implementation period
? To describe the exposure characteristics during the pre-and the post-implementation period, with respect to:
o Active substance
o Dose
o Treatment duration
? To describe the incidence of pregnancies exposed to oral retinoids during the pre- and the post-implementation period
? To stratify the key elements of the PPP described in the primary objective by oral retinoid substance
? To describe trends in the physician?s prescribing and monitoring practice of oral retinoids with respect to measures of the PPP (contraceptive use and performance of pregnancy tests) over the entire duration the study
STUDY DESIGN:
This is a multicountry, multisource, observational cohort study in females of childbearing potential receiving oral retinoids (i.e., acitretin, alitretinoin and isotretinoin) using a pre-post design. This study will cover time periods before and after the implementation of the updated RMMs related to the PPP update. The study will be based on secondary use of data extracted from established longitudinal healthcare databases (claims, primary care database, national registries). The pre-implementation period consists of 2 distinct phases, a 2-year phase (07/2014 to 06/2016) prior to the start of the referral in July 2016 and a 2.5-year phase between the start of the referral and the distribution of EM for the updated PPP in Q4 2018. The post-implementation period captures the 2-year phase after the distribution of the EM (01/2019 to 12/2020).
POPULATION:
The study population will consist of females of childbearing potential (13-49 years of age, inclusive) receiving oral retinoids (i.e., acitretin, alitretinoin and isotretinoin) in the outpatient setting (at officebased practices and outpatient departments at hospitals), during the pre-defined periods identified from the selected data sources in the European target countries (i.e., France, Germany, Spain, and Sweden).
INCLUSION CRITERIA:
? Female gender
? Childbearing potential (13-49 years of age, inclusive)
? Received or prescribed at least one prescription of the oral retinoids acitretin, alitretinoin, or isotretinoin in either the pre-implementation or post-implementation period
EXCLUSION CRITERIA:
All females in the age group 13 to 49 years with available information that they are not of childbearing potential before initiation of oral retinoids (such as records of hysterectomy or sterilisation) will be excluded.
Data for the oral retinoids acitretin, alitretinoin, and isotretinoin will only be extracted from databases in target countries where the respective active substance has been granted market authorisation.
No further exclusion criteria will be applied.
VARIABLES:
The exposure is defined as one or more prescriptions of oral retinoids (i.e., acitretin, alitretinoin, orisotretinoin) during one of the study periods. The following variables will be considered (if available):
patient age, oral retinoid prescribing and monitoring practice such as indication, length of prescription, treatment duration, and prescriber speciality, as well as PPP-specific variables such as prescriptions of contraceptive and ? if available – laboratory pregnancy testing (before, during, and after treatment). In addition, information on exposed pregnancies and outcomes (if available) will be provided.
DATA SOURCES:
The following established longitudinal data sources will be utilised for data extraction:
Claims databases
? France: System National d’Information Inter-Régimes de l’Assurance Maladie (SNIIRAM) of the Système National des Données de Santé (SNDS)
? Germany: Collective of insurants from company health insurance funds Primary care database
? Spain: Sistema d?Informació per al Desenvolupament de l?Investigació en Atenció Primària (SIDIAP)
National health registers
? Sweden: national drug-, patient-, and birth registers
Study size:
All females of childbearing potential receiving oral retinoids (i.e. acitretin, alitretinoin, isotretinoin) available in pre-defined periods of the selected databases will be included in the analysis.
The number of females of childbearing potential receiving oral retinoids was checked for a 3-year
period (2015-2017) in Germany, Spain, and Sweden. The number of patients is approximately 3,700 in Germany, 4,800 in Spain, and 20,500 in Sweden.
In France, only the number of boxes that was reimbursed in France in total (without any restriction to age and gender) is available without receiving ethical approval for the study, the number of approximately 1,041,000 boxes in one year suggests that the number of female patients of childbearing potential receiving oral retinoids will be sufficient for analysis.
DATA ANALYSIS:
Given the study objectives, the analyses will mainly be descriptive and will be conducted by country and study time periods (both pre-implementation periods and post-implementation period). Some comparisons will be made especially between the different study time periods.
The analyses will be provided for the overall class of oral retinoids (acitretin, alitretinoin and isotretinoin) and for the single active substances.
Results for key variables will be presented over time where patient numbers permit to provide insights on continuous trends capturing pre- and post-implementation periods.
In addition, an interrupted time series (ITS) analysis will be considered in case the conditions for this analysis will be met.

The ConcePTION project aims to build a platform that can use Real World Data (RWD) to generate Real World Evidence (RWE) regarding safety of medication use in pregnancy and breastfeeding for evidence-based decision-making in clinical and regulatory settings.

This project aims to demonstrate how secondary data sources across Europe can be used to study safety of medication use in pregnancy by conducting five methodologically diverse sub-projects.
Together, these sub-projects will demonstrate how the ConcePTION platform could facilitate future studies of medication use and safety based on data from health registries and linked databases in Europe in a distributed, timely, and scientifically sound way.

The demonstration sub-projects are:
1) Methods for controlling confounding by indication: application to medications for neuropathic pain
2) The effect of time varying confounders on long-term childhood outcomes: application to antidepressants and mental health disorders in pregnancy
3) Novel statistics to handle rare diseases and small sample sizes using Bayesian techniques: application to Multiple Sclerosis and Lupus (SLE) in pregnancy
4) Demonstrating solutions for studying intermittent medication exposures in diseases with episodic manifestations during pregnancy: application to medication for migraine in pregnancy
5) Studying medication exposure when disease is measured through accurate identification of an incident case: application to breast cancer and pregnancy.

Methods and Material: The sub-projects will utilize data from at least five different countries with geographic spread across Europe. The data sources will be selected based on sample size requirements as well as on availability and quality of variables, and available budget. Each country’s Data Access Provider (DAP) will be responsible for obtaining the necessary permissions for this project.
Data management and analysis will be done in each individual country/region using the ConcePTION common data model (CDM). Data will remain in the country of origin, and only aggregated results will be delivered to the ConcePTION platform. The studies will be conducted in line with the ENCePP Code of Conduct for scientific independence and transparency, and the FAIR (Findable, Accessible, Interoperable, Reusable) principles of the ConcePTION project.

Justificació
La hiperpotassèmia és una alteració electrolítica causada principalment per una insuficiència en l’excreció urinària de potassi per malaltia renal crònica (ERC), però també per alteracions o ús de fàrmacs que afecten el sistema renina-angioensina-aldosterona (SRAA). També pot aparèixer en casos de cetoacidosi diabètica o estat hiperglucèmic hiperosmolar.
La hiperpotassèmia es defineix com a concentració sèrica de potassi >5,5 mmol/L i es considera com lleu si el potassi sèric és 5,5-5,9 mmol/L, moderada si 6,0-6,4 mmol/L o greu >6,5 mmol/L.
S?han autoritzat dos nous fàrmacs per al tractament de la hiperpotassèmia en adults, destinats principalment per al tractament de la hiperpotassèmia crònica lleu o moderada en pacients amb malaltia renal crònica (MRC) o amb tractament amb inhibidors del SRAA. El tractament habitual en aquests casos es basa en la modificació de la dieta, l?ús de diürètics, el tractament de l’acidosi metabòlica crònica, evitar l’ús d’antiinflamatoris no esteroïdals o el tractament amb resines d’intercanvi catiònic (poliestirè sulfonat de sodi i calci).
Objectiu
Es plantegen dos estudis, un per avaluar la incidència d?hiperpotassèmia (estudi d?indicació-prescripció) i un altre per descriure la població tractada amb resines d?intercanvi catiònic (estudi de prescripció-indicació).

La fibrilación auricular (FA) es la arritmia crónica más frecuente, cuya prevalencia aumenta progresivamente con la edad. Su manejo en nuestro ámbito se lleva a cabo principalmente en atención primaria y uno de sus principales objetivos es la prevención de ictus mediante el uso de anticoagulantes antagonistas de la vitamina K (AVK) o anticoagulantes orales directos (ACOD). Los ACOD han demostrado ser al menos no inferiores a AVK en la prevención de ictus en sus respectivos ensayos clínicos pivotales. Pero los resultados de estos ensayos clínicos, que suelen incluir poblaciones demasiado seleccionadas, no se pueden extrapolar a todos los pacientes y circunstancias clínicas de la práctica diaria.
Nuestro objetivo principal es analizar la efectividad y seguridad de los diferentes ACOD en comparación con los AVK para prevención de ictus en FA no valvular. Los objetivos secundarios comprenden la evaluación de eventos tromboembólicos y hemorrágicos según la persistencia a los tratamientos anticoagulantes, el sexo, la edad, la insuficiencia renal crónica, o según si los pacientes son o no naïve para tratamiento anticoagulante.
También se pretenden analizar la efectividad y seguridad de los AVK según su tiempo en rango terapéutico del INR, y la mortalidad.
Se describirán las características de aquellos pacientes con FA no valvular que no reciben ningún tratamiento antitrombótico o reciben ácido acetilsalicílico y se explorará el uso de anticoagulantes orales en pacientes con neoplasia activa, sometidos a cirugía mayor, sometidos a cardioversiones eléctricas y pacientes que hayan sufrido un infarto de miocardio.
Para ello se realizará un estudio de cohortes retrospectivo incluyendo pacientes con FA no valvular que inician tratamiento con AVK o ACOD entre noviembre 2011 y diciembre 2018.

Els objectius dels estudis són per una banda descriure les indicacions per les quals es prescriu ivabradina i per l?altra descriure els tractaments utilitzats en la població amb insuficiència cardíaca i sí aquests tractaments s?utilitzen en les situacions clíniques adequades

4.2 Rationale and Background:
Oestrogen deficiency, described as a decline in the levels of circulating oestrogens, affects numerous tissues in postmenopausal women, including musculoskeletal, vascular, and urogenital systems (Archer 2010).
Oestrogen deficiency leads to a decrease in vaginal lubrication, which is an early hallmark of vulvar and vaginal atrophy (VVA). Symptoms of VVA include vaginal dryness, burning/itching, dyspareunia, vulvar pruritus, bleeding, particularly associated with sexual activity. VVA is also associated with urinary symptoms including urethral discomfort, frequency, haematuria, urinary tract infection, and dysuria (MacBride, Rhodes et al. 2010).
The prevalence of VVA ranges from 45%-57% (Levine, Williams et al. 2008, Santoro and Komi 2009). Current therapies include systemic oestrogens, local oestrogens and lubricants/moisturisers. Ospemifene is the first non-steroidal selective oestrogen receptor modulator (SERM) approved in the EU for the treatment of moderate to severe symptomatic vulvar and vaginal atrophy (VVA) in post-menopausal women who are not candidates for local vaginal oestrogen therapy .
The SERM class of drugs has been associated with an increased risk of venous thromboembolism (VTE) and cerebrovascular events (CVE). In the ospemifene clinical programme, which followed the Food and Drug Administration (FDA) Guidance for the Treatment of VVA, no increase in the incidence of VTE or CVE in the ospemifene cohort compared to placebo was observed. This Post-Authorisation Safety Study (PASS) is being undertaken to assess the safety of ospemifene in real life over a period of up to seven years in the US and five years in the European Union, EU, ( Spain, Italy and Germany). The PASS will involve comparative analyses between specified cohorts of women in the US and Germany arms of the study, and analyses of off-label use in the EU arms (Spain, Italy and Germany).
4.3 Research Question and Objectives:
Following is the research question of interest which is applicable to the Spain arm of the study:
What is the off-label use among ospemifene patients in Spain?
Additional questions of interest that are studied in other countries within the PASS include:
What is the incidence and risk of various side effects (such as VTE, CVE, endometrial hyperplasia, endometrial cancer, pelvic organ prolapse, urinary incontinence, gall bladder events, atrial fibrillation, renal failure, renal carcinoma, renal adenoma, liver tumours, thymic epithelial tumours, increased triglycerides, and vaginal bleeding) in a cohort of postmenopausal women newly prescribed ospemifene relative to (a) a cohort of postmenopausal women diagnosed with VVA but not treated for their condition with local or systemic oestrogens and (b) a cohort of postmenopausal women newly prescribed other SERM therapies (SERM comparison cohort) being utilised for oestrogen-deficiency conditions (i.e., non-cancer and non-infertility indications) or breast cancer prevention.
The objective of the study in Spain is to assess off-label use among ospemifene patients, including use in patients with vaginal bleeding or signs or symptoms of endometrial hyperplasia and endometrial cancer (contraindications)
4.4 Study Design:
The Spain arm of the PASS is an annual cross-sectional study using electronic medical records (EMR). This protocol addresses only the Spain database study arm, and summarises how off-label use of ospemifene will be investigated. All patients with at least one ospemifene prescription are eligible for the study
In order to minimise bias, new users (initiators) will be identified. A new user is defined as anyone in the database with at least 12 months of medical history and with at least one prescription of ospemifene. The study duration will be up to 5 years from study initiation, and annual data updates will be obtained from each data source. Annual data updates will continue until the earliest of (1) the target sample size being reached, or (2) 5 years elapsing since first EU availability.
4.5 Population:
There will be one study analysis population for the Spain arm of the study.
? Ospemifene Prescribed Population: any patient with a prescription of ospemifene (that is, all patients treated with ospemifene who are enrolled in the database). The use of ospemifene in any patients that are not postmenopausal (aged ?54 years) will be considered as off-label use.
Index Date: The index date (date of cohort entry) will be defined as the date of first ospemifene prescription
Inclusion Criteria: The Ospemifene Prescribed Population will include patients with at least one prescription or dispensation of ospemifene within the study period and at least 12 months of medical history (i.e., enrolment in the database or activity in the health system as a proxy for enrolment) prior to the index date.
Exclusion Criteria: There are no exclusion criteria.
Study Duration: The total study duration will be 5 years from the start of analysis. The maximum patient follow-up will be 5 years in the EU and 7 years in the US.
4.6 Variables:
Patient characteristics, medications, and select medical conditions at initial use of ospemifene. Exposure to ospemifene will be assumed to begin on the date of pharmacy dispensing or prescription, and continue to the date of the last prescription. The occurrence of specific indicators will be assessed if diagnosis or treatment occurs in the period extending from the 12 months preceding the first ospemifene to the date of the final prescription.
4.7 Data Source:
The data source for the Spain arm of the PASS is SIDIAP.
4.8 Study Size:
The Spain arm of the PASS will investigate off-label use of ospemifene: this is a descriptive study with an exploratory analysis (with no comparative component) of all patients with an ospemifene prescription, and therefore sample size calculations in this context can be interpreted as a forecast of patients using ospemifene.
4.9 Data Analysis:
Off-Label Use of Ospemifene
A descriptive analysis will be conducted examining the frequency of use of ospemifene that appears to be outside the indication in the EU label.
Patients who have been prescribed ospemifene will be categorised into three main groups. The first group will be designated ?On label? and patients will be included if there is clear evidence that the woman has a VVA diagnosis, is aged 54 years or over whilst receiving ospemifene prescription, and has no contraindications or off-label indicators. The second patient group will be designated ?Potentially on-label but lacking clear evidence of on-label indication?: all patients in this group will have neither contraindications nor other off-label indicators. The third and final patient group will be designated as ?Apparent off-label use?, and will have either contraindications, or have other off-label indicators.
The frequency distribution of patients by specific contraindication or other off-label indicator will be reported. In addition, an age distribution of patients with off-label indicators will be provided.
Post-Menopausal Women Who Are Not Candidates for Local Oestrogen Use (Restricted Conditions for Local Oestrogen Use)
A frequency distribution of patients prescribed ospemifene who have diagnosis or treatment for at least one of the following will be produced: history of melanoma, active treatment for breast cancer (including adjuvant therapy), history of breast cancer, history of endometrial cancer, porphyria, history of endometriosis and dexterity problems (Parkinson?s disease and/or history of stroke). Number and percentage of patients with conditions/indications which are both restricted for local oestrogen use and off-label/contraindicated for ospemifene will be highlighted.
4.10 Milestones:
The drug (ospemifene) is expected to be initially available in Italy, Spain and later in Germany. Ospemifene received approval from the US Food and Drug Administration (FDA) in 2013. Data collection will conducted annually after ospemifene is commercially available in the first European market. See Table A.1 (Appendices) for study milestones.

La farmacoterapia durante el embarazo y la lactancia implica el posible riesgo de trastornos congénitos y otras enfermedades en la descendencia, por lo que es necesario evaluar el balance beneficio-riesgo de todos los tratamientos farmacológicos antes de recetarlos en mujeres embarazadas o en período de lactancia.
El uso de drogas en el embarazo y la lactancia materna se ha evaluado a través de diferentes estudios y, últimamente, a través de estudios de bases de datos, que ofrecen ventajas tales como información vinculada a la madre y el período de seguimiento a largo plazo para las madres y los bebés, información sobre los resultados maternos y del parto. , e información sobre factores de confusión.
El uso de medicamentos durante el embarazo y la lactancia materna no se ha evaluado a través de registros de salud electrónicos en nuestro entorno y planeamos evaluarlo a través de un estudio de base poblacional realizado con datos del SIDIAP en todas las mujeres con embarazo y lactancia registradas en esta base de datos a lo largo de 2010-2018 .
Planeamos analizar el uso de drogas durante el embarazo y la lactancia materna, focalizándonos en trastornos cardiovasculares, neurológicos y psiquiátricos; analizar el uso de vacunas durante estos periodos; y para detectar posibles trastornos congénitos y otras enfermedades durante la infancia que pueden ser causadas por la exposición a medicamentos de las madres durante el embarazo y la lactancia.

La base del tractament farmacològic de la MPOC estable són els broncodilatadors (BD) inhalats. Per al tractament de manteniment s?utilitzen els agonistes beta 2 d?acció llarga (LABA) i/o els antagonistes muscarínics d?acció llarga (LAMA), combinats amb els corticoides inhalats (CI) en els pacients que presenten exacerbacions freqüents. Els BD d?acció curta es fan servir a demanda per a l?alleujament dels símptomes i en general no s?utilitzen com a tractament de manteniment.

Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, such as coronary heart disease (CHD), cerebrovascular disease and peripheral artery disease. In 2012, it was the leading cause of mortality worldwide, accounting for 31% of an estimated 56 million deaths from all causes. Long-term administration of aspirin, statins, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB) improve survival in high risk CHD patients. Nevertheless, adherence to prescribed medication is poor for long-term drug treatment in CVD.
In this cohort study we aim to assess the risk of major cardiovascular events and all-cause mortality according to the level of adherence to antiplatelet agents, beta-blockers, ACEI or ARB, and statins, in a population of incident cases of CHD, defined as patients with a first episode of acute coronary syndrome (ACS).
The main objective of the study is to assess the relationship between adherences to the four pharmacological groups recommended for secondary prevention and the clinical outcomes of cardiovascular morbidity and mortality in patients with established CHD.
This is a population-based retrospective cohort study of patients with a first episode of ACS registered in CMBD-HA of the ICS from 2006 to 2015.
We will estimate adherence to antiplatelet agents, beta-blockers, ACEI or ARB, and statins. The primary endpoints of the study are a composite endpoint including: all-cause mortality, ACS and ischaemic stroke; and the first of these three events.
We expect to find that adherent patients would have a lower risk of the primary endpoints compared with non-adherent patients.

Solifenacina/tamsulosina és la primera combinació a dosis fixes autoritzada per al tractament dels símptomes del tracte urinari inferior associats a la hiperplàsia prostàtica benigna en homes que no responen adequadament al tractament en monoteràpia. Es va comercialitzar el mes de gener de 2015 i el seu consum ha anat augmentant progressivament; segons dades del fitxer de prestació farmacèutica del Servei Català de la Salut, actualment hi ha aproximadament 5.000 pacients tractats amb aquest fàrmac.
Les guies de pràctica clínica recomanen associar un anticolinèrgic quan persisteixen els símptomes d?ompliment (freqüència miccional, urgència, incontinència) tot i el tractament amb un blocador ?1 adrenèrgic en monoteràpia.
Per tant, en aquests pacients hi ha actualment dues opcions, administrar un blocador ?1 adrenèrgic (el d?elecció és tamsulosina) i un anticolinèrgic urinari (els més utilitzats són solifenacina i tolterodina) per separat o donar la combinació a dosis fixes que estem avaluant (solifenacina/tamsulosina).
Les combinacions a dosis fixes permeten administrar menys formes orals a cada presa i tenen l?avantatge potencial de millorar l?adherència. No obstant això, en aquest cas es tracta d?un tractament simptomàtic sense impacte en l?evolució de la malaltia, en el que la manca de compliment, especialment a l?anticolinèrgic, està molt influenciada per la percepció de poca eficàcia i les reaccions adverses que provoca, més que per la complexitat de la pauta.
OBJECTIU: avaluar la persistència i l?adherència al tractament combinat de blocadors ?1 adrenèrgics i anticolinèrgics urinaris, administrats per separat o amb la única combinació a dosis fixes disponible actualment.

En abril de 2017 s?ha publicat l?actualització de les pautes harmonitzades del tractament farmacològic de la DM2 des de la perspectiva de l?atenció primària i comunitària, incorporant-hi les darreres novetats terapèutiques. En aquest context, és necessari descriure la situació actual al nostre àmbit d?atenció primària de l?ICS pel que fa a la prescripció i utilització de fàrmacs antidiabètics (no insulínics i insulines) i avaluar si aquesta prescripció i utilització segueixen els criteris establerts per les pautes d?harmonització.
Els objectius del present estudi són:
– Descriure quins són els fàrmacs pel tractament de la DM2 habitualment prescrits al nostre àmbit.
– Descriure la prevalença d?ús de cada fàrmac o grups de fàrmacs a la nostra població.
– Descriure el número de pacients tractats amb 1, 2, 3 o més de 3 fàrmacs per la DM2.
– Avaluar l?adequació de la prescripció dels fàrmacs per la DM2 a les pautes d?harmonització, segons les següents variables: filtrat glomerular, edat, HbA1c, IMC, anys d?evolució de la DM2.

Objectius: Càlcul de la n de pacients tributaris a rebre tractament amb lesinurad.
La hiperuricèmia asimptomàtica no es tracta, només la gota (clínica o demostració de cristalls en teixits). Així, els pacients ja tractats amb un hipouricemiant en monoteràpia (al·lopurinol o febuxostat) no controlats són els pacients candidats. L?objectiu d?uricèmia amb més consens és =6 mg/dl tot i que es recomana de 5 mg/dl en certes situacions. Per tant seria d?utilitat conèixer el nombre de pacients tractats en monoteràpia mal controlats

Se propone un estudio de casos y de controles de base poblacional destinado a evaluar el riesgo de accidente vascular cerebral (AVC), de tipo isquémico y/o hemorrágico, asociado a la exposición a un número de fármacos para los cuales previamente se ha descrito una asociación de incremento de riesgo en otros medios.

En concreto, se pretende evaluar si en nuestro medio se observa un incremento de riesgo de AVC isquémico asociado a la exposición a AINEs, antipsicóticos, antidepresivos sedantes y anticomiciales, así como si se observa un incremento de riesgo de AVC hemorrágicos asociado al uso de antiagregrantes y anticoagulantes.

Se prevé la inclusión de unos 12.000 casos incidentes de AVC y unos 120.000 controles similares en edad, sexo y procedencia geográfica obtenidos por muestreo de densidad.

Se realizará un análisis de regresión logística multivariante, consderando una serie de potenciales factores de confusión que incluirán patología cardiovascular asociada y nivel de riesgo cardiovascular, uso de fármacos destinados a la reducción del riesgo cardiovascular, y presencia de otros factores moduladores del riesgo de AVC.
Por otra parte, se prevé realizar el análisis en detalle de dos subgrupos de pacientes de especial interés: el de los pacientes con artrosis y el de los pacientes con demencia. La relevancia de estas poblaciones se debe a su elevada prevalencia, en el primer caso, y a su especial susceptibilidad y elevada incidencia de AVC, en el segundo.
Puesto que en ambos casos existen alternativas terapéuticas a los fámacos para los que se ha descrito el aumento de riesgo de AVC, en el supuesto de observar riesgos menores o de tipo protector para alguna de estas alternativas, se podrían derivar recomendaciones de estrategias preventivas específicas.

Irritable bowel syndrome (IBS) is a chronic, relapsing gastrointestinal condition characterised by abdominal pain, bloating, and changes in bowel habits. Prevalence estimations vary with the diagnostic criteria used, and in the United Kingdom (UK) were estimated between 9.5% and 22%. IBS can be classified according to Rome III criteria on the basis of the stool?s characteristics: IBS predominantly with diarrhoea (IBS-D); IBS predominantly with constipation (IBS-C); and IBS with mixed bowel habits (IBS-M), with approximately one third of IBS patients having each type. Retrospective cohort (patients newly prescribed linaclotide). The specific research objectives for this study are to: 1) Describe the characteristics of patients prescribed linaclotide at time of first prescription, overall and by specific subgroups of interest; 2) Describe the extend of linaclotide off-label use; 3) Describe the proportion and characteristics of patients prescribed linaclotide (overall, and by alleged indication [IBS-C vs. other indications] who experience discontinuation of linaclotide or switching from linaclotide to other drugs potentially used by patients with IBS-C; 4) Describe the duration of linaclotide treatment until discontinuation or switching. All analyses will be first performed separately in each of the study countries. In addition, for the primary study objectives, aggregated analyses with data from all three countries will be performed.

L’objectiu principal del projecte Somnia és avaluar el risc de narcolèpsia associat amb vacunes contra la influença pandèmica amb adjuvant AS03 . Somnia té els següents objectius: – Per avaluar el risc de narcolèpsia següent AS03 que conté les vacunes en països fora de l’estudi original VAESCO. Això permetrà l’avaluació de les poblacions de diferent genètica, sinó també en àrees del món on l’aparent falta de publicitat sobre la possible associació facilitarà una avaluació menys esbiaixada. – Per a determinar si existeix un risc de narcolèpsia després de la vacuna de la influença pandèmica amb adjuvant MF – 59. Això es farà en els països d’Europa i fora d’Europa l’ús d’aquesta vacuna en els nens. – Per perfeccionar i ampliar l’estudi actual VAESCO per: – L’avaluació de la solidesa de l’anàlisi VAESCO actual fins a la data . Això es farà mitjançant l’avaluació de les taxes de diagnòstic de la narcolèpsia amb el temps i avaluar l’exhaustivitat de la seva inclusió en les investigacions inicials . – Augmentar la potència de l’estudi actual VAESCO per a contiunar inscribint casos de narcolèpsia diagnosticats en el període d’estudi primari dels països europeus que han participat en VAESCO i altres països europeus.

Rationale and background: Agomelatine (Valdoxan, Thymanax) is a melatonergic agonist and 5-HT2C antagonist indicated for major depressive episodes in adults. Hepatotoxic reactions are an identified risk of agomelatine included in the European risk management plan. The goal of this post-authorisation safety study (PASS) is to evaluate the risk of hospitalisation for acute liver injury (ALI) associated with agomelatine as used in current medical practice in comparison with other antidepressant drugs.

Research question and objectives: Specific objectives will be to estimate the incidence rates of hospitalisation with ALI in adult patients initiating treatment with agomelatine and other antidepressants and to estimate the relative risk of hospitalisation for ALI comparing new users of agomelatine and other antidepressants with new users of citalopram.

Study design: This is a large, multinational, retrospective longitudinal cohort and nested case-control study of new users of agomelatine (main exposure of interest) and new users of citalopram (common reference group), fluoxetine, paroxetine, sertraline, escitalopram, mirtazapine, venlafaxine, duloxetine, and amitriptyline.

Population: The study cohort includes adults from the source populations with at least 12 months of continuous enrolment in the data source who have a first-recorded prescription of agomelatine or one of the other study antidepressants during the study period and had not received a prescription for the same study antidepressant within the prior 12 months. Patients with history of liver disease or risk factors for liver disease, chronic biliary or pancreatic disease; malignancy or other life-threating conditions; and women during pregnancy will be excluded from the study cohort.

Variables: The main exposures of interest will be current use of agomelatine and other selected antidepressants. The primary endpoint, common in all the study data sources, is defined as any patient with a hospital diagnosis for ALI identified with specific ICD-9-CM or ICD-10-CM diagnosis codes. The secondary endpoint is defined by specific and non-specific diagnoses and will be evaluated only in selected study databases (Spain and Denmark) in which validation of this less-specific outcome by review of medical records and/or results from liver tests will be implemented.
Data sources: Based on the results of a feasibility evaluation in 2013, the IACS and SIDIAP databases in Spain, the German Pharmacoepidemiological Database (GePaRD) in Germany, the national registries in Denmark, and the national registers in Sweden have been identified as the best candidate data sources in which to implement the study. All the research institutions except Karolinska Institutet in Sweden have confirmed interest in participating in the study. Researchers in Karolinska will decide during 2015 whether or not to participate.

Study size: The study size is driven by the uptake of agomelatine in the populations from which the automated data sources obtain data. We have estimated that approximately 65,000 to 92,000 users of agomelatine might be available for analysis during the study period. With this study size, and depending on the incidence of hospitalisation for ALI in the study populations, the minimum odds ratio to be detected in the nested case-control study with an 80% power ranges from 2.1 to 6.8 for the scenario with the lowest number of users of agomelatine and from 1.9 to 5.6 for the scenario with the highest number of users of agomelatine.

Data analysis: In the cohort study, crude incidence rates of hospitalisation for ALI will be estimated for current use of agomelatine and each study antidepressant. The Kaplan-Meier method will be used to estimate the crude cumulative incidence of ALI at monthly intervals after the first dispensing of agomelatine and each study antidepressant.
In the nested case-control study, cases and controls will be matched on age, sex, and index date of the event. For both the primary and secondary study endpoints, the risk of ALI in current users of agomelatine and current users of the other study antidepressants will be compared with the risk in current users of citalopram, adjusting for confounders using conditional logistic regression. A secondary analysis will be conducted to estimate the effect in current single users of the study antidepressants. Additional analyses will include the assessment of recent and past use of the study antidepressants.

This is a drug utilisation study (DUS) on the use of cilostazol in several European populations in the context of the cilostazol referral under Article 31 of Council Directive 2001/83/EC. The DUS is planned to be conducted using database sources to understand the characteristics of users of cilostazol, duration and patterns of cilostazol use, and prevalence of concomitant use of cilostazol and other drugs with which it may interact. The DUS is planned to be conducted in two phases. DUS1 will evaluate cilostazol as currently used in several European countries during the period from launch through 2011. DUS2 will be conducted after the implementation of changes to the summary of product characteristics (SmPC) and the follow-up communication activities with health care professionals (HCPs) and will evaluate the impact of these measures during the year 2014 in the same countries. DUS2 will be conducted using the same protocol as used in DUS1. Both DUS1 and DUS2 will include all the marketed products containing cilostazol in the countries, irrespective of brand.
The primary objectives of the DUS are the following:
– To describe the characteristics of new users of cilostazol according to (1) demographics, (2) baseline comorbidity including conditions listed in the SmPC and the risk management plan (RMP) as potential or identified safety concerns, (3) baseline and concurrent use of medications potentially interacting with
cilostazol, and (3) specific comorbidity.
– To describe the duration of the use of cilostazol and discontinuation patterns
Secondary objectives of the DUS are to (1) quantify and describe off-label prescribing, (2) describe dosage patterns of the use of cilostazol, (3) to assess the proportion of patients who are hospitalised for any cause while treated with cilostazol, and (4) identify the medical specialties of physicians prescribing cilostazol.
Cohort study of new users of cilostazol identified in five proposed European population-based automated health databases from Spain (two databases), Germany, the United Kingdom, and Sweden (see Data Sources).

The goal of this study is to assess the effectiveness of minimization measures through the description of the utilization of dronedarone based on information captured in selected databases since the implementation of these measures. Starting from all labeling recommendations, the objectives of the study have been limited to the measurement of the data elements routinely available in European databases. Thus, the primary objectives of this study are therefore among patients initiating dronedarone since implementation of minimization measures: 1) Estimate the proportion of patients with a history of or current heart failure prior to the dronedarone initiation; 2) Estimate the proportion of patients with concomitant use of contraindicated drugs; 3) Estimate the proportion of patients receiving ECGs at least every 6 months whilst on dronedarone therapy; 4) Estimate the proportion of patients with serum creatinine testing and liver function test (LFT) monitoring The secondary objectives of this study are to: 5) Compare the proportions observed for each of the objectives listed above in the patients initiating dronedarone since implementation of minimization measures to proportions observed in the patients treated with dronedarone before. 6) Determine the effectiveness of minimization measures over the following outcomes: death, heart failure, stroke, myocardial infarction, coronary heart disease, renal failure, hepatitis, hepatic failure and hospital admission. 7) Determine the suitability of data from SIDIAP database.

Title: Cilostazol drug utilisation study Rationale and background: Drug utilisation study (DUS) on the use of cilostazol in several European populations in the context of the cilostazol referral under Article 31 of Council Directive 2001/83/EC. The DUS is planned to be conducted using database sources to understand the characteristics of users of cilostazol, duration and patterns of cilostazol use, and prevalence of concomitant use of cilostazol and other drugs with which it may interact. A second DUS is planned after the implementation of changes to the cilostazol summary of product characteristics (SmPC) and the follow-up communication activities with health care professionals (HCPs). Research question and objectives: The primary objectives of the DUS are the following: – To identify new users of cilostazol since it became available in each country: Spain, UK, Germany, and Sweden. – To describe the characteristics of new users of cilostazol according to (1) demographics, (2) baseline comorbidity including conditions listed in the SmPC and the risk management plan (RMP) as potential or identified safety concerns, (3) baseline and concurrent use of medications potentially interacting with cilostazol, and (3) specific comorbidity. – To describe the duration of the use of cilostazol and discontinuation patterns. Secondary objectives of the DUS are to (1) quantify and describe off-label prescribing, (2) describe dosage patterns of the use of cilostazol, and (3) identify the medical specialties of physicians prescribing cilostazol. Study design: Cohort study of new users of cilostazol identified in five proposed European population-based automated health databases from Spain, Germany, the United Kingdom, and Sweden. New users of cilostazol will be characterised in terms of demographics, comorbidity, and comedications at the date of receiving the first prescription for cilostazol (start date). Population: The source population includes all individuals registered in the study databases since the date of cilostazol availability in each country. The study period is defined as the time between the date of cilostazol availability and the latest date of data availability in each database.

OBJETIVOS Objetivo principal: analizar la utilización de fármacos para el manejo de la fibrilación auricular de causa no valvular con especial atención a los fármacos antitrombóticos. Objetivos específicos: Describir el manejo antitrombótico actual: tratamiento anticoagulante y/o antiagregante. Evaluar la efectividad de los diferentes tratamientos antitrombóticos en condiciones reales de uso según incidencia de accidentes cerebrovasculares y la seguridad según incidencia de hemorragias graves que requieren ingreso hospitalario. Determinar el coste anual por paciente de los diferentes tratamientos antitrombóticos. Describir el manejo farmacológico de la frecuencia y ritmo y determinar el coste anual por paciente de estos fármacos. Analizar la irrupción del nuevo antitrombótico dabigatran en cambios de tratamiento, efectividad y seguridad durante el primer año y en costes. METODOLOGÍA: estudio de cohortes retrospectivo del tratamiento y características de la población diagnosticada de fibrilación auricular. Se utilizará la base de datos SIDIAP que recoge de forma anonimizada los datos de las historias clínicas de la estación clínica (ECAP) de 280 equipos de atención primaria del Instituto Catalán de la Salud (cobertura al 85% de la población). Se estimará la efectividad, seguridad y costes de los tratamientos antitrombóticos.

Este es un estudio observacional retrospectivo, la estrategia de tratamiento de los pacientes no esta decidida previamente por el protocolo sino que el tratamiento de los pacientes es el recomendado por el médico participante de acuerdo a su práctica clínica habitual.

JUSTIFICACION
– Las nuevas prescripciones de estatinas en prevención cardiovascular en España se realizan mayoritariamente en prevención primaria (75 -90%).
– La indicación de las nuevas prescripciones de estatinas en prevención primaria se considera adecuada sólo en un tercio de los pacientes.
– La comercialización de rosuvastatina en el mercado español representará el 10% de las nuevas prescripciones de estatinas durante el primer año, en pacientes que estén tomando estatinas o no las hayan tomado con anterioridad.

OBJETIVOS
– Describir la distribución de las nuevas prescripciones de estatinas en una muestra de pacientes en Cataluñá en el período de un año desde la fecha de comercialización de rosuvastatina.
– Describir las características clínicas y epidemiológicas de los usuarios de rosuvastatina.
– Describir la distribución de las nuevas prescripciones de rosuvastatina en prevención cardiovascular primaria y secundaria.
– Analizar la adecuación de las nuevas prescripciones de rosuvastatina a las recomendaciones de las guías de práctica clínica en Cataluña.
– Analizar si las condiciones de utilización de rosuvastatina son adecuadas según la información de la ficha técnica: indicación, dosis, pauta, contraindicaciones, y posibles interacciones.

DISEÑO: Estudio observacional longitudinal retrospectivo.

POBLACIÓN: Pacientes adultos (mayores de 18 años) que reciben una nueva prescripción entre septiembre de 2009 hasta agosto de 2010 de estatina o tengan un cambio en su tratamiento con estatinas, bien sea por cambios dentro del grupo de las estatinas, cambios en la dosis previamente prescrita o cambio en el tratamiento debido a la adicción al tratamiento de ezetimibe o fibratos, como tratamiento de la dislipemia en prevención cardiovascular primaria o secundaria.

CRITERIOS INCLUSION:
1. Hombres y mujeres mayores de 18 años
2. Pacientes que reciben una nueva prescripción de estatina (simvastatina, atorvastatina, pravastatina, rosuvastatina u otras).
3. Pacientes que reciben uno o más cambios en la prescripción* de estatinas (simvastatina, atorvastatina, pravastatina, rosuvastatina u otras).
* Pacientes que realiza un cambio en la prescripción de estatina: paciente que está tomando una estatina o la ha tomado en algún momento en los seis meses anteriores y cambia de prescripción de estatina o cambia de dosis de estatina o se le añade ezetimibe o un fibrato

CRITERIOS EXCLUSION:
1. Pacientes de los que no se disponga de información suficiente para recoger los datos.

DURACION DEL ESTUDIO POR PACIENTE: De obtendrán datos retrospectivos de los pacientes desde la inclusión o inicio del tratamiento hasta agosto de 2011.

VARIABLES DEL ESTUDIO
(a) Variable Principal
– Tratamiento hipolipemiante y parámetros asociados
(b) Otras variables
– Características epidemiológicas
– Parámetros analíticos
– Tratamientos
– Patologías