Cost utility of fractional exhaled nitric oxide monitoring for the management of children asthma

Introduction Fractional exhaled nitric oxide is a simple, non-invasive measurement of airway inflammation with minimal discomfort to the patient and with results available within a few minutes. This study aimed to evaluate the cost-effectiveness of asthma management using fractional exhaled nitric oxide monitoring in patients between 4 and 18 years of age. Methods A Markov model was used to estimate the cost-utility of asthma management using fractional exhaled nitric oxide monitoring versus asthma management without using fractional exhaled nitric oxide monitoring (standard therapy) in patients between 4 and 18 years of age. Cost data were obtained from a retrospective study on asthma from a tertiary center, in Medellin, Colombia, while probabilities of the Markov model and utilities were obtained from the systematic review of published randomized clinical trials. The analysis was carried out from a societal perspective. Results The model showed that fractional exhaled nitric oxide monitoring was associated with a lower total cost than standard therapy (US $1333 vs. US$1452 average cost per patient) and higher QALYs (0.93 vs. 0.92 average per patient). The probability that fractional exhaled nitric oxide monitoring provides a more cost-effective use of resources compared with standard therapy exceeds 99% for all willingness-to-pay thresholds. Conclusion Asthma management using fractional exhaled nitric oxide monitoring was cost-effective for treating patients between 4 and 18 years of age with mild to moderate allergic asthma. Our study suggests evidence that could be used by decision-makers to improve clinical practice guidelines, but this should be replicated in different clinical settings

For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?

Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, especially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis

Toxicity results after treatment with Electronic Brachytherapy in patients with endometrial cancer

Poster Session [EP-2226] Purpose or Objective To analyse the toxicity outcomes after treatment with Electronic Brachytherapy (XB) in postsurgical endometrial cancer patients treated at our medical centre. Material and Methods Prospective study in which we selected 94 patients, between September/2015 and September/2017, that received treatment with XB administered twice a week after endometrial cancer surgery, with IMRT planificati on. The patients were divided in two groups: Group 1 (57/94) considered high risk received external beam radiotherapy (46Gy) followed by XB (15Gy in 5Gy fractions) and group 2 (37/94) considered intermediate risk received exclusive XB (25Gy in 5Gy fraction s). We analysed the median dose in bladder, rectum and sigmoid D2cc, V50, V35 with XB comparing the doses with Ir192. The vaginal mucosa, gastrointestinal (GI) and genitourinary (GU) toxicities were analysed with the Common Terminology Criteria for Adverse Events (CTCAE 4.0) scale. Results The median dose in bladder with XB vs. Ir192 was: 2cc 62.9 vs. 69.9%, V50 7.1 vs. 12.6Gy, V35 15 vs. 28.1. In rectum XB vs. Ir192 was: D 2cc 64.01% vs. 67.7%, V50 7.8 vs. 10.9Gy, V35 16.5 vs. 31.8Gy. In sigmoid XB vs. Ir 192 was: D 50.37%vs. 58.0%, V50 8.8 vs. 16.2Gy, V35 21.2 vs. 37.5Gy. The median follow- up was 11 months (range 1 - 23, 9 months). In group 1, acute vaginal mucositis (G1) was observed in 35.08% of the patients, GI toxicity (G1) in 5.26% and GU toxicity (G1) in 10.52%. In group 2, we observed acute vaginal mucositis G1 in 45% of the patients and G2 in 10.81%, GI toxicity (G1) occurred in 2.7% and GU toxicity (G1) was present in 16.21%. There was no grade 3 or greater toxicity in any of the groups. Late toxici ty was observed in only 4 patients: Mucositis (G1) in 3 patients and GU toxicity (G1) in 1 patient. Conclusion The dose received by the organs at risk with the XB is less compared to Ir192, with a good coverage of the PTV. The greater toxicity was observe d immediately after the treatment was finished with an important reduction of the symptoms after 6 months. This technique shows excellent results as for toxicity

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

Obesity-associated adipose tissue enlargement is characterized by an enhanced proinflammatory status and an elevated secretion of adipokines such as leptin and cytokines such as TNF-alpha. Among the different mechanisms that could underlie the interindividual differences in obesity, epigenetic regulation of gene expression has emerged as a potentially important determinant. Therefore, twenty-seven obese women (age: 32-50 years; baseline Body Mass Index, BMI: 34.4±4.2 Kg/m2) were prescribed an eight-week Low-Calorie-Diet and epigenetic marks were assessed. Baseline and endpoint anthropometric parameters were measured and blood samples were drawn. Genomic DNA and RNA from adipose tissue biopsies were isolated before and after the dietary intervention. Leptin and TNF-alpha promoter methylation were measured by MSP after bisulfite treatment and gene expression was also analyzed. Obese women with a successful weight loss (≥5% of initial body weight, n=21) improved the lipid profile and fat mass percentage (-12%, p<0.05). Both systolic (-5%, p<0.05) and diastolic (-8%, p<0.01) blood pressures significantly decreased. At baseline women with better response to the dietary intervention showed lower promoter methylation levels of leptin (-47%, p<0.05) and TNF-alpha (-39%, p=0.071) than the non-responder group (n=6), while no differences were found between responder and non-responder group in leptin and TNF-alpha gene expression analysis. These data suggest that leptin and TNF-alpha methylation levels could be used as epigenetic biomarkers concerning the response to a Low-Calorie-Diet. Indeed, methylation profile could help to predict the susceptibility to weight loss as well as some comorbidities such as hypertension or type 2 diabetes

An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers

A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss

Epigenetics could help to explain individual differences in weight loss after an energy-restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty-five overweight or obese men participated in an 8-wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI-TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight-loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloric-diet-induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss

Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center

© 2007 Russo and Katsicas; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority