Avaluació epidemiològica dels efectes indesitjables greus dels analgèsics i antiinflamatoris no esteroïdals

Títol obtingut de la portada digitalitzadaConsultable des del TDXPenden

Evaluación de la respuesta y seguridad a diferentes esquemas de tratamiento antirretroviral en Colombia

Establecer variables asociadas a fallas terapéuticas, adherencia al tratamiento, cambio de esquema y efectos indeseables asociados al tratamiento de VIH/SIDA

Humoral and cellular response in convalescent COVID-19 lupus patients

Systemic lupus erythematosus; Translational immunologyLupus eritematós sistèmic; Immunologia translacionalLupus eritematoso sistémico; Inmunología traslacionalIn SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8+T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8+ T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy

Sobreutilización de inhibidores de la acidez gástrica en pacientes pediátricos

Objetivos: Evaluar los patrones de prescripción de ranitidina y omeprazol en pacientes pediátricos ingresados en un hospital de niños; la adecuación de dichas prescripciones y los costos generados por prescripciones incorrectas. Pacientes y Métodos: estudio de utilización de medicamentos para observar pacientes ingresados en el Hospital de Niños (Córdoba –Argentina) durante 1 mes. Resultados: Durante el mes de estudio ingresaron 680 pacientes, de los cuales 415 (61%) recibieron inhibidores de la acidez gástrica (IAG). De estos, 330 pacientes (79,5%) no presentaron factores de riesgo para desarrollar úlcera por estrés, y en 293 pacientes (70,6%) las indicaciones se consideraron incorrectas. Sólo 81 pacientes (19,5%) presentaron indicaciones y dosis correctas de IAG. Se encontró una relación de la prescripción con el ingreso a quirófano y con el uso concomitante de corticoides a dosis bajas. El consumo innecesario de IAG generó un gasto directo mensual de US$ 470,42. Conclusiones: Este estudio pone de manifiesto una alarmante sobreutilización de IAG en la población pediátrica del Hospital de Niños. Existe una brecha entre las pruebas científicas y la práctica clínica cotidiana en la utilización de IAG. Se deberían implementar estrategias educativas en farmacoterapéutica, utilizando protocolos de actuación y auditorias farmacológicas con posterior evaluación, para mejorar la utilización de medicamentos y otorgar a los pacientes una medicina académica, efectiva, segura y de alta calidad

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008–2015)

Anticoagulants; Europe; Non valvular atrial fibrillationAnticoagulants; Europa; Fibril·lació auricular no valvularAnticoagulantes; Europa; Fibrilación auricular no valvularAims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008–2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).The project has received support from the European Medicines Agency under the Framework service contract (nr EMA/2015/27/PH) with regard to the reopening of competition no. 3. K. Janhsen (Witten/Herdecke University, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany (UW/GH)) and A. Heeke (AOK NORDWEST, Kopenhagener Straße 1, 44269 Dortmund, Germany). R. Gerlach and M. Tauscher (National Association of Statutory Health Insurance Physicians of Bavaria, Elsenheimerstr. 39, MD-80687 Munich, Germany). The authors from the BIFAP database would like to acknowledge the excellent collaboration of the primary care general practitioners and pediatricians, and also the support of the regional governments to the database. This study is based in part on data from the ‘base de datos para la investigación Farmacoepidemiológica en Atención Primaria’ (BIFAP) fully financed by the Spanish Agency on Medicines and Medical Devices (AEMPS). The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the EMA (European Medicines Agency) or one of its committees or working parties, or AEMPS (Agencia Española de Medicamentos y Productos Sanitarios). The authors thank Alethea Charlton for her support reviewing and editing the English. The authors thank SIDIAP (Sistema d’informació per al Desenvolupament de Investigació en Atenció Primària) for providing the data with respect to CPRD, approval of the study protocol was granted by the Independent Scientific Advisory Committee of the Medicines and Healthcare Products Regulatory Agency (protocol 17_089R)

Indications related to antidepressant prescribing in the Nivel-PCD database and the SIDIAP database

Altres ajuts: Acord transformatiu CRUE-CSICAntidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings

Efectividad del tratamiento antirretroviral en pacientes con Diagnóstico de VIH/SIDA de dos ciudades de Colombia

Métodos: Estudio descriptivo en 134 pacientes en tratamiento para VIH/SIDA en Pereira y Manizales entre el 1 de julio de 2008 y el 30 de junio de 2009. Se evaluó la carga viral, conteo de linfocitos CD4, esquemas antirretrovirales, dosis diaria prescrita, tiempo evolución de enfermedad, duración de terapia, antecedentes de enfermedades oportunistas, costos de medicamentos. Resultados: Predominio masculino (91 hombres vs 43 mujeres), promedio de edad de 39 años y 59 meses de evolución de la enfermedad. Todos recibían esquemas a Dosis Diarias Definidas recomendadas. La terapia era efectiva en el 74,5% de los pacientes (carga viral 400 copias/ml). Se pudo establecer que la falta de adherencia al tratamiento y el antecedente de haber tenido otras 2 infecciones de transmisión sexual se asociaban con mayor riesgo de no controlar la infección por VIH. El valor promedio de los medicamentos por año por paciente fue de € 2.865. Conclusiones. La falta de adherencia al tratamiento sigue siendo uno de los problemas más importantes para garantizar la efectividad, por lo cual los programas de control del VIH/SIDA deben asegurarla

Estudi d'utilització d'antifúngics sistèmics a l'Hospital Universitari Vall d'Hebron

Objectius: Descriure les principals característiques de la utilització dels antifúngics sistèmics a l'Hospital Universitari Vall d'Hebron (HUVH) i avaluar la seva adequació. Metodologia: Estudi de prescripció-indicació en pacients majors de 16 anys amb seguiment prospectiu de 40 casos incidents consecutius. Limitats a 10 els casos de fluconazole, es realitza una anàlisi descriptiva ponderada. S'avalua l'adequació segons les recomanacions de la Infectious Diseases Society of America (IDSA). Resultats: El fluconazole va ser el fàrmac més emprat (74,8%; IC del 95%: 60,7-88,9), seguit del voriconazole. L'ús més habitual va ser l'empíric-anticipat (53,4%; IC del 95%: 28,6-78,1) i la indicació més freqüent la profilaxi d'infecció fúngica invasiva (25,0%; IC del 95%: 2,4-47,5). Es van considerar adequades el 71,7% (IC del 95%: 49,1-94,3) de les indicacions, el 100% (IC del 95%: 100-100) dels fàrmacs seleccionats, el 51,2% (IC del 95%: 21,8-80,6) de les dosis i el 61,7% (IC del 95%: 32,6-90,7) de les durades. Conclusions: Els resultats suggereixen que a l'HUVH es fa una prescripció raonada dels antifúngics sistèmics però caldria millorar el seu ús empíricanticipat i específic. Cal interpretar-los amb cautela per la manca de precisió i la dificultat per valorar la situació clínic

Synergism interaction between genetic polymorphisms in drug metabolizing enzymes and NSAIDs on upper gastrointestinal haemorrhage: a multicenter case-control study

Genetic variation; Non-steroidal anti-inflammatory drugs; Upper gastrointestinal haemorrhageVariació genètica; Fàrmacs antiinflamatoris no esteroides; Hemorràgia gastrointestinal superiorVariación genética; Medicamentos antiinflamatorios no esteroideos; Hemorragia gastrointestinal superiorBackground 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.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 Investigaciońn 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

A multicenter case–control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users

Gastroenterology; PharmacogeneticsGastroenterologia; FarmacogenèticaGastroenterología; FarmacogenéticaBleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.This work was supported by a grant from Instituto de Salud Carlos III [PI12/02414]/Plan Estatal de 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 Investigación Sanitaria [PI021512, PI021364, PI020661, PI021572]; Ministry of Health & Consumer Affairs, Spain [SAF2002-04057]; Galician Regional Authority, Spain [PGIDIT03PXIC20806PN]; Department of Health of the Basque Country [03/11092 and 11/111103]; and Fundacion vasca de innovacin e investigacin sanitarias [OSIBG19/002 and OSIBG18/105]. The genotyping service was carried out at CEGEN-PRB3-ISCIII; Instituto de Salud Carlos III and ERDF [PT17/0019, of the PE I + D + I 2013–2016]