Exclusive enteral nutrition (EEN) is recommended as a first-line therapy to induce remission of Crohn's disease (CD) and is considered as effective as corticosteroid treatment. However, the dietary ...restriction causes lack of adherence and poor tolerance to the therapy. Partial enteral nutrition (PEN), which allows for the ingestion of some food, could be a better tolerated alternative, but it is unknown whether it is as effective at inducing CD remission as EEN. The aim of this systematic review is to analyze the available evidence on PEN as a remission induction therapy in CD. A literature search was conducted using the MEDLINE (via PUBMED) and Cochrane Library databases following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Clinical trials in pediatric and adult patients were included. The risk of bias was assessed following the Cochrane Collaboration methodology. The selected studies showed variable but high response rates to PEN and EEN. Limitations regarding the wide heterogeneity between the studies included in this review should be considered. Although more studies are needed, according to our results, PEN combined with a highly restrictive diet seems to be as effective as EEN in inducing remission of CD.
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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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.
Aims
The aim of this study was to test whether a newly designed polypharmacy‐based scale would perform better than Charlson's Comorbidity Index (CCI) to predict outcomes in chronic complex adult ...patients after a reference Emergency Department (ED) visit.
Methods
We built a polypharmacy‐based scale with prespecified drug families. The primary outcome was 6‐month mortality after the reference ED visit. Predefined secondary outcomes were need for hospital admission, 30‐day readmission, and 30‐day and 90‐day mortality. We evaluated the ability of the CCI and the polypharmacy‐based scale to independently predict 6‐month mortality using logistic regression, receiver operating characteristic (ROC) curves, and cumulative survival curves using Kaplan–Meier estimates and the log‐rank test for three‐category distributions of the polypharmacy‐based scale and the CCI. Finally, we sought to replicate our results in two different external validation cohorts.
Results
We included 201 patients (53.7% women, mean age = 81.4 years), 162 of whom were admitted to the hospital at the reference ED visit. In separate multivariable analyses accounting for gender, age and main diagnosis at discharge, both the polypharmacy‐based scale (P < .001) and the CCI (P = .005) independently predicted 6‐month mortality. The polypharmacy‐based scale performed better in the ROC analyses (area under the curve AUC = 0.838, 95% confidence interval CI = 0.780–0.896) than the CCI (AUC = 0.628, 95% CI = 0.548–0.707). In the 6‐month cumulative survival analysis, the polypharmacy‐based scale showed statistical significance (P < .001), whereas the CCI did not (P = .484). We replicated our results in the validation cohorts.
Conclusions
Our polypharmacy‐based scale performed significantly better than the CCI to predict 6‐month mortality in chronic complex patients after a reference ED visit.
The frequency of some Cystic Fibrosis (CF) Transmembrane Conductance Regulator gene (CFTR) mutations varies between populations. Genetic testing during newborn screening (NBS) for CF can identify ...less common mutations with low clinical expression in childhood and previously considered mild but not fully characterized, such as the mutation p.Val232Asp (c.695T > A). The aim of this study was to describe CF patients with the V232D mutation. We identify CF children with the V232D mutation detected by NBS and compare them with CF adults with this mutation whose diagnosis was prompted by clinical symptoms in the same period. We studied clinical, biochemical, spirometric, and prognostic features in both populations. NBS program tested 276,523 children during a period of 14 years (2003-2017) and identified 54 cases of CF. Six children (11%) had the V232D mutation. Over the same period, 5 adults (age 37.6 ± 16.29 years old) with symptoms of CF and this mutation were also diagnosed. Follow-up duration was mean 10.1 years for adults and mean 6.5 years for children. In the adult group, lung function was impaired at diagnosis in all patients (Forced Expiratory Volume1-FEV1-67.12% ± 13.09) and worsened in children tested during evolution (FEV1first: 113%; FEV1last: 64%). Pancreatic insufficiency was present in adult group, with recurrent pancreatitis in 1 present. Although with less clinical expression in children, V232D is associated with pulmonary and pancreatic involvement during adulthood and CF cannot be considered mild. This mutation is present in 11% of all patients diagnosed with CF in our region. Its inclusion in some NBS programs should be taken into account in order to improve the prognosis of affected children.
Aims
Previous studies demonstrated the relationship between hypochloraemia and poor prognosis in patients hospitalized for acute heart failure (AHF). However, the usefulness of chloride in clinical ...practice remains uncertain, notably in very old patients with predominantly heart failure (HF) with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic impact of chloride in a cohort of very aged patients with AHF and the possible existence of different phenotypes of hypochloraemia with distinct clinical significance.
Methods and results
It was an observational study of 429 patients hospitalized for AHF in which chloraemia was measured. Two different phenotypes of hypochloraemia were identified by their relationship with estimated plasma volume status (ePVS) as a proxy of intravascular congestion. The endpoint of interest was time to all‐cause mortality and the composite of death and/or HF readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 85 (78–92) years, 266 (62%) were women, and 80% had HFpEF. After multivariable analysis, chloraemia, but not natraemia, was associated with the risk of death and HF readmission in a U‐shaped pattern. The phenotype characterized by hypochloraemia and low ePVS (depletional) was associated with an increased risk of mortality when compared with patients with normochloraemia hazard ratio (HR) 1.86, P = 0.008. In contrast, hypochloraemia with high ePVS (dilutional) had no prognostic significance (HR 0.94, P = 0.855).
Conclusions
In very old patients hospitalized with AHF, plasma chloride was associated with the risk of death and HF readmission in a U‐shaped pattern and could potentially be used for congestion phenotyping.
Aim
The aim of the study was to develop and implement a protocol for the prevention and treatment of catheter related intraluminal thrombosis in a paediatric intensive care unit
Methods
A ...computerised search was carried out on MEDLINE, through PubMed, using the medical subject heading ‘central venous catheter’, ‘central venous access device’, ‘central venous line’ associated with ‘occlusion’, ‘obstruction’, ‘catheter‐related thrombosis’, ‘critically ill patients’ and ‘thrombolytic therapy’. References of reviewed articles were also searched for relevant titles as well as non‐randomised controlled trials and series of cases when no information of higher level of evidence was available.
Results
With the information gathered, a protocol for the prevention and treatment of catheter related intraluminal thrombosis was elaborated and those recommendations that best suit our environment were included. They were agreed upon by a broad panel of professionals working in the Pediatric Intensive Care Unit and the Pharmacy Department.
Conclusions
Due to the variety of options available for the pharmacotherapeutic management of intraluminal catheter thrombosis, one measure to improve the quality of the therapy and to diminish the variability in the prescription could be the implementation of a protocol as described in this paper.
Summary
Background/objective
Pharmaceutical care is needed in hepatitis C virus (HCV)‐infected patients treated with direct‐acting antivirals (DAA). We describe the implementation of a comprehensive ...pharmaceutical care programme (CPCP) for HCV‐infected patients treated with DAA in a tertiary‐care hospital and provide data about health outcomes and costs.
Methods
Quasi‐experimental study between 1 April 2015 and 30 June 2016. A group of hospital pharmacists collaborating on HCV infection implemented interventional measures for validation of drug prescriptions, detection of clinically relevant drug‐drug interactions and adverse drug events (ADEs), and patient education. Quality, health and cost‐effectiveness outcomes were evaluated.
Results
A total of 1070 patients were enrolled. Pharmacists made 327 interventions that led to the prevention of 299 (91.4%) medication errors, 16 of which were grade G‐H (NCC MERP classification). The main reasons for the pharmacist's intervention were management of 143 drug‐drug interactions. The overall sustained virologic response at week 12 posttreatment (SVR12) rate was 93.0% (95% CI 91.4‐94.6). The SVR12 was higher than 90.0% in all populations, except in genotype 3 patients (86.0%, 95% CI 78.7‐93.9), decompensated cirrhotic patients (81.1%, 95% CI 69.7‐92.6) and transplant recipients (86.8%, 95% CI 76.7‐96.9). ADEs occurred in 85.5% of the study patients, but only 1.0% (11 patients) experienced an ADE that led to premature discontinuation. The total cost of treatment was €18 279 225 (€17 083 per patient). The most cost‐effective treatment was selected in 93.1% of patients.
Conclusions
The implementation of a CPCP developed by hospital pharmacists in patients treated with DAAs for HCV infection is an effective approach that improves patient safety and education. The active involvement of the pharmacist in improving adherence to local guidelines promoted the selection of the most cost‐effective treatment in the majority of cases.
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