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OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last 3 years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorized or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13.9% of them are not marketed, 46.5% are in a situation of non-financing, under study or without a request for financing, and 4.6% are financed for a specific pediatric subpopulation. 52.7% are original drugs, 4.7% are generic, 38.8% are biological, 3.8% are biosimilar, and 17.8% are orphan drugs. 57.36% of these medicines obtain the pediatric indication due to extension of the indication and 42.64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorized indications are increasingly available in the pediatric population and the trend is to extend the indication of authorized drugs to the adult population. However, barriers in terms of financing and marketing need to be expedite and overcome to facilitate access to them.
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Aprovação de Drogas , Espanha , Humanos , Criança , Produção de Droga sem Interesse Comercial/economia , Produção de Droga sem Interesse Comercial/estatística & dados numéricos , Pediatria , Pré-Escolar , AdolescenteRESUMO
OBJECTIVE: To determine the prevalence of reconciliation errors on admission to hospital in the pediatric onco-hematological population in order to check whether they are similarly susceptible to these reconciliation errors as adults and to describe the characteristics of the patients who suffer them. METHODS: A 12-month prospective, multicentre study of medication reconciliation on admission in the pediatric onco-hematological population to assess the incidence of reconciliation errors and to describe the characteristics of the patients. RESULTS: Medication reconciliation was performed in 157 patients. At least a medication discrepancy was detected in 96 patients. Of the discrepancies detected, 52.1% were related to patient's new clinical situation or by the physician, while 48.9% were determined to be reconciliation errors. The most frequent type of reconciliation error was the "omission of a medication", followed by "a different dose, frequency or route of administration". A total of 77 pharmaceutical interventions were carried out, 94.2% of which were accepted. In the group of patients with a number equal to or greater than 4 drugs in home treatment, there was a 2.1-fold increase in the probability of suffering a reconciliation error. CONCLUSIONS: In order to avoid or reduce errors in one of the critical safety points such as transitions of care, there are measures such as medication reconciliation. In the case of complex chronic pediatric patients, such as onco-hematological patients, the number of drugs as part of home treatment is the variable that has been associated with the presence of medication reconciliation errors on admission to hospital, and the omission of some medication was the main cause of these errors.
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Erros de Medicação , Reconciliação de Medicamentos , Adulto , Humanos , Criança , Estudos Prospectivos , Erros de Medicação/prevenção & controle , Admissão do Paciente , HospitaisRESUMO
OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last three years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorised or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13,9% of them are not marketed, 46,5% are in a situation of non-financing, under study, or without a request for financing, and 4,6% are financed for a specific pediatric subpopulation. 52,7% are original drugs, 4,7% are generic, 38,8% are biological, 3,8% are biosimilar and 17,8% are orphan drugs. 57,36% of these medicines obtain the pediatric indication due to extension of the indication and 42,64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorised indications are increasingly available in the paediatric population and the trend is to extend the indication of authorised drugs to the adult population. However, barriers in terms of financing and marketing need to be expedited and overcome to facilitate access to them.
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OBJECTIVE: To determine the prevalence of reconciliation errors (RE) on admission to hospital in the paediatric onco-haematological population in order to check whether they are similarly susceptible to these RE as adults and to describe the characteristics of the patients who suffer them. METHODS: A 12-month prospective, multicentre study of medication reconciliation on admission in the paediatric onco-haematological population to assess the incidence of RE and describe the characteristics of the patients in whom they occur. RESULTS: Medication reconciliation was performed in 157 patients. At least 1 medication discrepancy was detected in 96 patients. Of the discrepancies detected, 52.1% were justified by the patient's new clinical situation or by the physician, while 48.9% were determined to be RE. The most frequent type of RE was the "omission of a medication", followed by "a different dose, frequency or route of administration". A total of 77 pharmaceutical interventions were carried out, 94.2% of which were accepted. In the group of patients with a number equal to or greater than 4 drugs in home treatment, there was a 2.1-fold increase in the probability of suffering a RE. CONCLUSIONS: In order to avoid or reduce errors in one of the critical safety points such as transitions of care, there are measures such as medication reconciliation. In the case of complex chronic paediatric patients, such as onco-haematological patients, the number of drugs as part of home treatment is the variable that has been associated with the presence of medication RE on admission to hospital, with the omission of some medication being the main cause of these errors.
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Erros de Medicação , Reconciliação de Medicamentos , Criança , Humanos , Hospitais , Erros de Medicação/prevenção & controle , Admissão do Paciente , Estudos ProspectivosRESUMO
BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.
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Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improve patient outcomes, and reduce resistance. To assess the effectiveness of ASPs, it is necessary to have indicators that can be widely used. Defined daily dose (DDD) was designed by WHO for the adult population as a consumption indicator. However, there are no DDDs adapted to the pediatric population. The main objective of this study is to establish the most appropriate DDD values in this population. An observational, retrospective, multicenter study was conducted. Antimicrobial prescriptions were collected from pediatric wards of seven Spanish tertiary hospitals for 2 years. The DDDs obtained from the prescriptions were compared with the theoretical DDDs agreed upon in the first stage. To select the optimal DDD, the following were analyzed: power value, magnitude obtained from the differences in the DDD, statistical significance, and degree of agreement in the stipulated doses. A total of 4788 prescriptions were collected. Pediatric DDD was defined for 30 different antimicrobials. A potency >80% was obtained in 24 antibiotics. 51.2% of the selected DDD correspond to Phase I and 39.5% from Phase II. Pediatric DDD of different antimicrobials was obtained, providing an indicator that can be used globally in different hospitals to analyze the consumption and efficacy of ASPs.
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OBJECTIVES: To evaluate the impact of a quality-of-care improvement program implemented in emergency departments (EDs) in a Spanish autonomous community with the aim of reducing the use of unrecommended drugs when treating infants for acute bronchiolitis. MATERIAL AND METHODS: Before-after quasi-experimental intervention study. We retrospectively included infants aged 12 months or less who were treated for acute bronchiolitis in 24 Spanish national health system hospital EDs in December during 2 epidemic periods: in 2018, before implementing the program, and in 2019, after implementation. Data collected included epidemiologic information, clinical and care details, and clinical course. The program consisted of providing informative material and training sessions before the epidemic period started. RESULTS: A total of 7717 episodes (4007 in 2018 and 2710 in 2019) were identified. Epidemiologic and clinical characteristics did not differ between the 2 periods. ED use of the following treatments decreased between the 2 periods: salbutamol, from 29.4% (95% CI, 28.8%-30.8%) in 2018 to 10.6% (95% CI, 9.6%-11.6%) in 2019; epinephrine from 6.0% (95% CI, 5.3%-6.8%) to 0.9% (95% CI, 0.7%-1.3%); and hypertonic saline solution fell from 8.2% (95% CI, 7.3%-9.1%) to 2.1% (95% CI, 1.7%-2.6%) (P.001, all comparisons). Prescriptions for salbutamol on discharge fell from 38.7% (95% CI, 36.9%-40.4%) to 10.6% (95% CI, 9.6%-11.6%) (P.001). Admissions and readmissions did not change, and the median time (interquartile range) spent in the ED fell from 81 (44-138) minutes to 66 (37-127) minutes (P.001). CONCLUSION: The quality-of-care improvement initiative was able to decrease the number of unrecommended therapeutic interventions for acute bronchiolitis. However, we identified great variations between EDs, suggesting that training and assessment of impact should continue.
OBJETIVO: Evaluar el impacto de una iniciativa de mejora realizada en los servicios de urgencias (SU) de una comunidad autónoma para reducir el uso de fármacos no recomendados en lactantes con bronquiolitis aguda (BA). METODO: Estudio cuasi-experimental analítico del tipo "antes y después de una intervención". Se incluyeron de forma retrospectiva todas las BA en niños # 12 meses atendidas en los SU de 24 hospitales públicos durante el mes de diciembre de dos periodos epidémicos: 2018 (preintervención) y 2019 (postintervención). Se recogieron variables epidemiológicas, clínicas, asistenciales y evolutivas. La intervención consistió en difundir material informativo y realizar actividades formativas previas al periodo epidémico. RESULTADOS: Se incluyeron 7.717 episodios (2018: 4.007 y 2019: 3.710). No existieron diferencias en las características epidemiológicas y clínicas. El empleo de salbutamol en los SU descendió del 29,4% [intervalo de confianza del 95% (IC 95%): 28,8-30,8] en 2018 al 10,6% (IC 95%: 9,6-11,6) en 2019 (p 0,001), el de adrenalina del 6,0% (IC 95%: 5,3-6,8) al 0,9% (IC 95%: 0,7-1,3) y el de suero salino hipertónico del 8,2% (IC 95%: 7,3-9,1) al 2,1% (IC 95%: 1,7-2,6) (p 0,001). La prescripción al alta de salbutamol se redujo del 38,7% (IC 95%: 36,9-40,4) al 10,6% (IC 95%: 9,6-11,6) (p 0,001). La tasa de ingreso y la tasa de readmisión no cambiaron y la mediana de tiempo de estancia en los SU se redujo 81 minutos [rango intercuartil (RIC) 44-138] a 66 (RIQ: 37-127) (p 0,001). CONCLUSIONES: La iniciativa de mejora ha conseguido disminuir la tasa de intervenciones terapéuticas no indicadas en BA. Sin embargo, existe una gran variabilidad entre los diferentes SU por lo que la estrategia y la medición de su impacto deben mantenerse en el tiempo.
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Bronquiolite , Humanos , Lactente , Estudos Retrospectivos , Doença Aguda , Bronquiolite/tratamento farmacológico , Serviço Hospitalar de Emergência , Albuterol/uso terapêuticoRESUMO
INTRODUCTION AND AIMS: The incidence of paediatric inflammatory bowel disease has increased in recent decades. The aim of the present study was to evaluate the role of proactive and serial monitoring of tumour necrosis factor (TNF) inhibitor levels to maintain clinical remission and mucosal healing in the follow-up of paediatric patients with Crohn disease (CD). METHODS: Prospective study that included all patients diagnosed with CD and treated with adalimumab or infliximab between May 2015 and November 2020 who underwent serial and proactive monitoring of TNF inhibitor levels. RESULTS: The study included 30 patients, 21 male (70%). The mean age at diagnosis was 11.3 years (SD, 2.0), the mean age at initiation of TNF inhibitors was 12.6 years (SD, 1.9) with a mean duration of follow-up of 27.1⯱â¯9.1 months. Clinical remission was defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) of less than 12.5 and mucosal healing as a Mucosal Inflammation Non-invasive Index (MINI) of less than 8. During the follow-up, patients were in clinical remission in 87.1% of the visits, presented with mild disease in 11.4% and with moderate disease in 1.5%, and mucosal healing was assumed in 83% of the visits. The rates of clinical remission and mucosal healing at 1, 2, and 3 years of follow-up were 83.3%, 95.8%, 92.8%, and 86.7%, 87.5% and 85.7%, respectively. CONCLUSIONS: Proactive and serial monitoring of serum TNF inhibitor levels may make it possible for patients to maintain clinical remission and mucosal healing in the maintenance phase, with individualised optimization of the required dosage and minimization of secondary loss of response.
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Doença de Crohn , Inibidores do Fator de Necrose Tumoral , Criança , Humanos , Masculino , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/diagnóstico , Seguimentos , Estudos Prospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , FemininoRESUMO
BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.
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Anti-Infecciosos , Gestão de Antimicrobianos , Antibacterianos/uso terapêutico , Ceftriaxona , Ciprofloxacina , Humanos , Lactente , Recém-NascidoRESUMO
Juvenile polyposis syndrome (JPS) is a rare disease with an autosomal dominant inheritance pattern characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. The most frequent signs and symptoms are recurrent abdominal pain, rectal bleeding, anemia, and iron deficiency. The treatment of JPS is symptomatic, requiring serial endoscopic polypectomies or intestinal resections in the most severe cases. We describe the clinical case of a patient with JPS with a childhood juvenile polyposis phenotype because of a mutation on the SMAD4 gene, who received treatment with sirolimus successfully.
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BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.
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BACKGROUND: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. METHODS: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. RESULTS: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). CONCLUSION: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
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Chronically active ulcerative colitis (UC) constitutes a challenge in an era where medical therapeutic options have increased while experience with colectomies has decreased. The change in the therapeutic paradigm of the disease means that patients with chronically active UC are being managed waiting to find their therapeutic target. We present 2 cases of children with chronically active UC who did not respond to intravenous steroids nor sequential therapy. A response was obtained with ustekinumab and tofacitinib, 2 drugs widely used in adults but still with little evidence in children. Highlighting the important role of patients and their families helped decision-making, facilitating the work of the medical team. With multidisciplinary management and close follow-up, they have been able to avoid surgery entering complete clinical remission.
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AIMS: Identifying DNA variants associated with trough serum anti-tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti-TNF levels and whether these variants are differential markers for infliximab and adalimumab. METHODS: We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty-one polymorphisms were genotyped using real-time PCR. Trough serum anti-TNF levels were measured using enzyme-linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti-TNF drugs was analysed by Fisher exact test, student's t-test and logistic regression. RESULTS: The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). CONCLUSION: Genotyping of these DNA variants before starting treatment may help to select the best anti-TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti-TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti-TNF levels.
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Doenças Inflamatórias Intestinais , Inibidores do Fator de Necrose Tumoral , Adalimumab , Adolescente , Criança , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Infliximab , Farmacogenética , Inibidores do Fator de Necrose Tumoral/farmacocinéticaRESUMO
OBJECTIVES: Inflammatory bowel disease (IBD) is more complex in children and they will have to live with the disease for much longer. For this reason, it is necessary to optimize treatment. The polymorphisms associated with the response to anti-tumor necrosis factor (TNF) drugs in adults with IBD have not been analyzed in children. The aim of the study was to identify genetic variants associated with the long-term response to anti-TNF drugs in children with IBD. METHODS: An observational, longitudinal, ambispective cohort's study was conducted. We recruited 209 anti-TNF-treated children diagnosed with IBD and genotyped 21 polymorphisms previously studied in adults with Crohn disease (CD) using real-time PCR. The association between single-nucleotide polymorphisms (SNPs) and time-to-failure was analyzed using the log-rank test. RESULTS: After multivariate analysis, 3 SNPs in IL10, IL17A and IL6 were significantly associated with response to anti-TNF treatment among patients diagnosed with CD (rs1800872-HR, 4.749 (95% confidence interval [CI] 1.156-19.517), P valueâ<â0.05; rs2275913-HR, 0.320 [95% CI 0.111-0.920], P value â<â0.05; and rs10499563-HR, 0.210 [95% CI 0.047-0.947], P value 0.05, respectively). None of these SNPs were associated with response to infliximab in adults diagnosed with CD. Among patients diagnosed with ulcerative colitis (UC), 1 SNP in LY96 was significantly associated with response to anti-TNF treatment (rs-11465996-HR, 10.220 [95% CI 1.849-56.504] P valueâ<â0.05). CONCLUSIONS: Genotyping of these DNA variants before starting treatment may help to identify children who are long-term responders to anti-TNF drugs, and thus tailor treatment of pediatric IBD.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adulto , Criança , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Infliximab/uso terapêutico , Necrose , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/genéticaRESUMO
Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2-∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.
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Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/farmacologia , Transcriptoma/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adolescente , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lactente , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Infliximab/uso terapêutico , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , RNA Mensageiro/genética , Receptores Tipo II do Fator de Necrose Tumoral/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteína Smad7/biossíntese , Proteína Smad7/genética , Receptor 2 Toll-Like/biossíntese , Receptor 2 Toll-Like/genética , Resultado do Tratamento , Receptor Gatilho 1 Expresso em Células Mieloides/biossíntese , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , alfa-Defensinas/biossíntese , alfa-Defensinas/genéticaRESUMO
BACKGROUND AND OBJECTIVE: To identify antiretrovirals drug interaction databases (ADID) and evaluate its structural quality. MATERIAL AND METHOD: A literature search in Medline and a grey literature search were conducted. The identified ADID underwent scrutiny based on exclusion criteria and structural quality (4 minimum quality criteria: stratification by level of severity, classification by level of evidence, bibliographic data, description of the clinical management) and 11 criteria that provide the relative importance (specific weight). We analyzed the degree of compliance of the criteria in each ADID and the degree of compliance of each criterion in all ADID. RESULTS: We identified 81 databases but only 8 of them were included for the analysis. Only 3 of them reached the minimum criteria: HIV-Drug interactions, Clinical Care Options HIV (The Drug-Drug Interactions Tool) and InteraccionesHIV.com. All the databases included are presented on computerized support, organized by active drug and describe clinical management; 7 of them inform about the interaction mechanism of action and have multicheck structure that speeds up the search; 4 declare they have no conflict of interest and stratifies by level of severity; 5 contain bibliographic reference; none of them classifies by level of evidence. CONCLUSIONS: There are many antiretroviral interaction databases available. The knowledge about their quality structure will help provide appropriate information.