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[EN] Background Interindividual genetic variations contribute to differences in patients' response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH. Materials and methods We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin). Results We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3.30 (95%CI: 1.24-8.80), RERI = 4.39 (95%CI: 0.70-8.07); non-aspirin NSAIDs: S = 3.42 (95%CI: 1.12-10.47), RERI = 3.97 (95%CI: 0.44-7.50)], and rs4809957:A>G [any NSAID: S = 2.11 (95%CI: 0.90-4.97), RERI = 3.46 (95%CI: -0.40-7.31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [ORaspirin(+),wild-type: 2.22 (95%CI: 0.69-7.17) vs. ORaspirin(+),genetic-variation: 7.72 (95%CI: 2.75-21.68)], yet larger sample size is needed to confirm this observation. Conclusions The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption. KEY MESSAGES Multicenter case-control study of the effect of genetic variations involved in drug metabolism on upper gastrointestinal haemorrhage (UGIH) induced by NSAIDs (aspirin and non-aspirin). There is a statistically significant additive synergism interaction between certain genetic polymorphisms and NSAIDs on UGIH: rs2180314:C>G and rs4809957:A>G. The joint effect of each of these single nucleotide polymorphisms and NSAIDs on UGIH is more than three times higher than the sum of their individual effects. Genetic profiling and personalized prescriptions would be useful in managing the risks and benefits associated with NSAIDs. This study was supported by grants from: Carlos III Health Institute (P I12/02414, of the P E I+D+I 2012-2016); Fondo Europeo de Desarrollo Regional (FEDER); the Novartis, Pfizer and Dr Esteve pharmaceutical companies; the Health Research Fund/Fondo de Investigacio ~nn Sanitaria (P I021512, P I021364, P I020661, and P I021572); Ministry of Health & Consumer Affairs, Spain (SAF2002-04057); Galician Regional Authority, Spain (P GIDIT03P XIC20806P N); Department of Health of the Basque Country (03/11092 and 11/111103); Fundacion Vasca de innovacion e investigacion sanitarias (OSIBG19/002 and OSIBG18/105). The genotyping service was carried out at CEGEN-P RB3-ISCIII; Carlos III Health Institute and ERDF (P T17/0019, of the P E I+D+I 2013-2016). The funding sources do not have any role in the study design; data collection, analysis and interpretation; writing the manuscript; and in the decision to submit the article for publication.

Objective The aim of this study was to assess whether the CYP2C9∗2 and/or ∗3 variants might modify the risk for NSAID-related upper gastrointestinal bleeding (UGIB) in NSAID users. Patients and methods We conducted a multicenter, case-control study in which cases were patients aged more than 18 years with a diagnosis of UGIB, and controls were matched (1 : 3) by sex, age, date of admission, and hospital. Exposure was defined as the mean number of defined daily doses (DDDs) of NSAIDs metabolized by CYP2C9 in the week preceding the index date. Three DDD categories were defined (0, ≤0.5, and >0.5). Exposure was constructed taking both NSAID use and CYP2C9 polymorphisms into account. Patients of non-European origin were excluded from the analysis. Results A total of 577 cases and 1343 controls were finally included in the analysis: 103 cases and 89 controls consumed NSAIDs metabolized by CYP2C9, and 88 cases and 177 controls were CYP2C9∗3 carriers. The adjusted odds ratios (aORs) of UGIB associated with the CYP2C9∗2 and wild-type alleles proved to be similar [OR=8.79 (4.50-17.17) and 10.15 (2.92-35.35), respectively] and lower than those of the CYP2C9∗3 allele [aOR=18.07 (6.34-51.53)] for consumers taking more than 0.5 DDDs of NSAIDs metabolized by CYP2C9. Grouping genotypes into carriers and noncarriers of the CYP2C9∗3 variant resulted in aORs of 16.92 (4.96-57.59) for carriers and 9.72 (4.55-20.76) for noncarriers, where DDDs were greater than 0.5. Conclusion The presence of the CYP2C9∗3 variant increases the risk for UGIB associated with NSAID for DDDs greater than 0.5. The presence of the CYP2C9∗2 allele shows no such effect.

Las desigualdades socioeconómicas son una causa de mortalidad y morbilidad superior a la mayoría de factores de riesgo, especialmente en el entorno urbano. Se llevó a cabo una revisión sistemática de la evidencia científica, en la que se incluyó artículos en inglés, castellano, portugués e italiano y se excluyeron estudios de baja evidencia, y en los que no se analizaba la relación entre mortalidad y nivel socioeconómico en un entorno urbano. La selección de artículos se llevó a cabo por dos revisores independientes y la extracción de datos se realizó con tablas de evidencia. Se obtuvieron 1.509 registros y se incluyeron 24. En todos los trabajos se observó mayor mortalidad en las áreas con peores indicadores de privación. Se observó asociación con patologías cardiovasculares en seis estudios, en cuatro con patologías pulmonares y en tres con SIDA, infecciones y parasitosis y cirrosis. Los estudios incluidos presentan resultados poco consistentes y limitaciones metodológicas importantes que impiden la comparación entre estudios y la extracción de conclusiones relevantes. Socioeconomic inequalities cause more disease and death than most risk factors, especially in cities. This systematic review of the scientific evidence included articles in English, Spanish, Portuguese, and Italian and excluded studies with low levels of evidence and those that did not analyze associations between mortality and socioeconomic status in urban settings. Articles were selected by two independent reviewers, and data extraction used evidence tables. A total of 1,509 records were obtained, and 24 were included. All the studies showed higher mortality rates in poorer areas. Six studies showed an association with cardiovascular diseases, four with lung diseases, and three with AIDS, infectious and parasitic diseases, and cirrhosis. The selected studies showed low consistency in the results and important methodological limitations that prevented comparisons between studies or the extraction of relevant conclusions. As desigualdades socioeconômicas são uma causa de mortalidade e morbidade superior à maioria dos fatores de risco, especialmente no ambiente urbano. Foi realizada uma revisão sistemática da evidência científica, na qual foram incluídos artigos em inglês, espanhol, português e italiano, e da qual foram excluídos estudos de baixa evidência, onde não constava análise da relação entre mortalidade e nível socioeconômico no ambiente urbano. A seleção de artigos foi efetuada por dois revisores independentes e a extração de dados foi feita através de tabelas de evidência. Foram obtidos 1.509 registros e incluídos 24. Em todos os trabalhos, foi observada maior mortalidade nas áreas com os piores indicadores de privação. Observou-se uma associação com patologias cardiovasculares em seis estudos, com patologias pulmonares, em quatro deles, e com a AIDS, infecções, parasitoses e cirrose em três. Os estudos incluídos apresentam resultados pouco consistentes e importantes limitações metodológicas, impedindo a comparação entre estudos e a inferência de conclusões relevantes. SI

Esta Tesis pretende profundizar en el estudio de las variantes polimórficas CYP2C9*2 Y CYP2C9*3 Y en su influencia en la variabilidad interindividual de las reacciones adversas gastrointestinales de los antiinflamatorios no esteroideos (AINE).

Uno de los indicadores más relevantes para evaluar la seguridad del paciente es la incidencia de eventos adversos (EA). Las úlceras por presión (UPP) son un EA con una incidencia muy elevada en las unidades de cuidados intensivos. El objetivo de este estudio es valorar la efectividad de una intervención formativa en prevención de UPP a través de la valoración de la incidencia y la gravedad de las lesiones en una unidad de cuidados intensivos quirúrgicos. Se llevó a cabo un estudio cuasi experimental de controles antes-después. Los resultados muestran que la incidencia de UPP disminuye tras la intervención formativa. One of the most relevant indicators to assess patient safety is the incidence of adverse events (AE). Pressure Ulcers (PU) are an AE with a high incidence in intensive care units. The aim of this study is to evaluate the effectiveness of a formative intervention on prevention of PU through the assessment of the incidence and the severity of PU in the pre and the post intervention periods, in an intensive care surgical unit. We have carried out a quasi experimental study of pre and post controls. The results show that the incidence of PU is lower after the formative intervention.

Uno de los indicadores más relevantes para evaluar la seguridad del paciente es la incidencia de eventos adversos (EA). Las úlceras por presión (UPP) son un EA con una incidencia muy elevada en las unidades de cuidados intensivos. El objetivo de este estudio es valorar la efectividad de una intervención formativa en prevención de UPP a través de la valoración de la incidencia y la gravedad de las lesiones en una unidad de cuidados intensivos quirúrgicos. Se llevó a cabo un estudio cuasi experimental de controles antes-después. Los resultados muestran que la incidencia de UPP disminuye tras la intervención formativa.

Uno de los indicadores más relevantes para evaluar la seguridad del paciente es la incidencia de eventos adversos (EA). Las úlceras por presión (UPP) son un EA con una incidencia muy elevada en las unidades de cuidados intensivos. El objetivo de este estudio es valorar la efectividad de una intervención formativa en prevención de UPP a través de la valoración de la incidencia y la gravedad de las lesiones en una unidad de cuidados intensivos quirúrgicos. Se llevó a cabo un estudio cuasi experimental de controles antes-después. Los resultados muestran que la incidencia de UPP disminuye tras la intervención formativa. One of the most relevant indicators to assess patient safety is the incidence of adverse events (AE). Pressure Ulcers (PU) are an AE with a high incidence in intensive care units. The aim of this study is to evaluate the effectiveness of a formative intervention on prevention of PU through the assessment of the incidence and the severity of PU in the pre and the post intervention periods, in an intensive care surgical unit. We have carried out a quasi experimental study of pre and post controls. The results show that the incidence of PU is lower after the formative intervention.