Few genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of ...considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.
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Hematological conditions are prevalent disorders that are associated with significant comorbidities and have a major impact on patient care. Concerning new tools for the care of these patients, the ...number of health apps aimed at hematological patients is growing. Currently, there are no quality analyses or classifications of apps for patients diagnosed with hematological conditions.
The aim of this study is to analyze the characteristics and quality of apps designed for patients diagnosed with hematological conditions by using the Mobile App Rating Scale (MARS).
We performed an observational, cross-sectional descriptive study of all smartphone apps for patients diagnosed with hematological conditions. A search was conducted in March 2021 using the following terms: anemia, blood cancer, blood disorder, hematological cancer, hematological malignancy, hematological tumor, hematology, hemophilia, hemorrhage, lymphoma, leukemia, multiple myeloma, thalassemia, thrombocytopenia, and thrombosis. The apps identified were downloaded and evaluated by 2 independent researchers. General characteristics were registered, and quality was analyzed using MARS scores. Interrater reliability was measured by using the Cohen κ coefficient.
We identified 2100 apps in the initial search, and 4.19% (88/2100) of apps met the inclusion criteria and were analyzed. Of the 88 apps, 61% (54/88) were available on Android, 30% (26/88) were available on iOS, and 9% (8/88) were available on both platforms. Moreover, 7% (6/88) required payment, and 49% (43/88) were updated in the last year. Only 26% (23/88) of the apps were developed with the participation of health professionals. Most apps were informative (60/88, 68%), followed by preventive (23/88, 26%) and diagnostic (5/88, 6%). Most of the apps were intended for patients with anemia (23/88, 26%). The mean MARS score for the overall quality of the 88 apps was 3.03 (SD 1.14), ranging from 1.19 (lowest-rated app) to 4.86 (highest-rated app). Only 47% (41/88) of the apps obtained a MARS score of over 3 points (acceptable quality). Functionality was the best-rated section, followed by aesthetics, engagement, information, and app subjective quality. The five apps with the highest MARS score were the following: Multiple Myeloma Manager, Hodgkin Lymphoma Manager, Focus On Lymphoma, ALL Manager, and CLL Manager. The analysis by operating system, developer, and cost revealed statistically significant differences in MARS scores (P<.001, P<.001, and P=.049, respectively). The interrater agreement between the 2 reviewers was substantial (k=0.78).
There is great heterogeneity in the quality of apps for patients with hematological conditions. More than half of the apps do not meet acceptable criteria for quality and content. Most of them only provide information about the pathology, lacking interactivity and personalization options. The participation of health professionals in the development of these apps is low, although it is narrowly related to better quality.
Resumen Introducción: la elaboración de nutriciones parenterales (NP) es un proceso complejo y con alta probabilidad de aparición de errores. Objetivo: analizar los errores detectados en el control ...gravimétrico (CG) y de productos (CP) utilizados realizado en las NP elaboradas. Métodos: se realizó un análisis prospectivo en el que durante tres años (enero de 2016 a diciembre de 2018) se pesaron las NP elaboradas. Se utilizó el programa informático MedicalOne Parenteral®, que calcula el peso teórico teniendo en cuenta la densidad y el volumen. Cada NP elaborada se pesaba para obtener el peso real. El error gravimétrico (%) (EG = (peso real - peso teórico) x 100 / peso teórico) se consideró correcto dentro del intervalo de ± 5 %. El CP consistía en la comprobación de los productos y los volúmenes utilizados con la hoja de elaboración. Resultados: se realizó el control de 28.761 NP. Se pesaron 20.612 NP de adultos (NPA), siendo incorrectas 124 (0,6 %). De las 1203 NP de pacientes pediátricos no neonatos (NPP), 15 (1,25 %) fueron incorrectas, y de las 6946 de neonatos (NPN), 164 (2,96 %). Respecto al CP se detectaron 71 errores en las NPA (0,70 %), 6 (1,34 %) en las NPP y 5 (0,21 %) en las NPN. Los errores fueron: añadir más volumen de un componente 38 (46,34 %), añadir menos volumen 17(20,73 %) y producto erróneo 27 (32,93 %). Conclusiones: el control de calidad realizado permitió detectar errores producidos durante la elaboración y evitó que llegaran al paciente. Se detectaron en el CG más NP incorrectas entre las NPN. Con el CP, el error mayoritario fue añadir más volumen de un componente.
Introduction: parenteral nutrition (PN) compounding is a process with a high probability of errors. Objective: to analyze PN compounding errors detected using a gravimetric control (GC) and a ...component verification control (CVC). Methods: a prospective analysis was carried out during a three-year period (January 2016 to December 2018). The MedicalOne Parenteral® software program was used to calculate the theoretical weight of each PN based on density and volume. Each elaborated PN was weighed to obtain the real weight. Gravimetric error (%) ((real weight - theoretical weight) x 100 / theoretical weight) was considered correct if within the ± 5 % interval. The CVC consisted of checking that the correct ingredients and volumes were added according to the PN order. Results: during the study period a total number of 28,761 PNs were checked out; 20,612 adult PNs (APN) were weighed and 124 were considered incorrect (0.60 %). Of the 1,203 non-neonatal pediatric PNs (NPPN), 15 (1.25 %) were incorrect, and of the 6,946 neonatal PNs (NPN), 164 (2.96 %) were incorrect. Regarding the CVC, 71 errors were detected in the APN (0.70 %), 6 (1.34 %) in the NPPN, and 5 (0.21 %) in the NPN group. The total number of errors included: adding more volume of one component 38 (46.34 %), adding a wrong component 27 (32.93 %), and absent volume of one component 17 (20.73 %). Conclusions: the quality control carried out allowed to detect errors during the preparation of PNs and prevented them from reaching the patient. More incorrect NPNs were detected through GC. The main error detected with CVC was adding more volume of a component.
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association ...between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.
Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to ...identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.
We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs.
Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3).
We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
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•Baseline gene expression in blood associates with the response to anti-TNF drugs.•RNA-seq identified 102 genes associated with the response to anti-TNF drugs.•PRTN3, LTF, LCN, and CEACAM8 are overexpressed in responder children.•Cancer-related genes impact the response to anti-TNF drugs.•Overexpressed genes in responder children directly link to TNF processes.
Summary
Objectives
This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment‐experienced ...HIV‐1‐infected patients with sustained virological suppression.
Methods
Observational, prospective study. Study population included all treatment‐experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end‐point was defined as the proportion of patients who maintained virological suppression at week 96 by intention‐to‐treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed.
Results
One‐hundred forty‐six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow‐up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P<.001), TC/HDL cholesterol ratio (0.4 mg/dL, P=.019) and triglycerides (42.0 mg/dL, P<.001). A slight decrease in glomerular filtration rate was observed (4.3 mL/min/1.73 m2, P<.001). Switching to RPV/FTC/TDF improved adherence in the subgroup of patients whose previous treatment was based on a twice‐daily schedule, although differences did not reach statistical significance. Switching to RPV/FTC/TDF reduced the annual per‐patient antiretroviral cost by €1744 (P<.001).
Conclusions
In virologically suppressed patients, the switch to a RPV/FTC/TDF regimen was associated with a mild but maintained improvement in lipid parameters and a significant reduction in costs. However, the relatively high rates of virological failure and treatment discontinuation because of adverse events make this combination a less favourable choice over other regimens currently available.
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 (
= 27) and non-responders to anti-TNF therapy (
= 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
method. Before initiation and after 2 weeks of treatment the expression of
was decreased in patients who were considered as non-responders (
value < 0.05). Changes in expression were also observed for
at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of
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
gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
and
need to be validated in larger studies.
Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This ...study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD.
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