Isotope Ratio Mass Spectrometry (IRMS) Versus Laser-Assisted Ratio Analyzer (LARA)

This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [¹³C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [¹³C]urea + Ensure and in 117 patients 75 mg [¹³C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy-based tests were negative. A value >5 was considered positive. Breath samples with insufficient CO₂ levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall values of the two machines with both [¹³C]urea 100 mg + Ensure and [¹³C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean –1.3, +6.3, and –9.4) than with the latter urea dosage and test meal (mean –1.2, +5.2 and –8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [¹³C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [¹³C]urea dosages is very effective also for posttherapy evaluation of H. pylori status.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Psychotropic medications and risk for falls among community-dwelling frail older people: an observational study

BACKGROUND: Injuries due to falls are one of the most important public health concerns for all ages, but especially for frail elderly people. Although a small number of falls have a single cause, the majority have many different causes resulting from the interactions between intrinsic or extrinsic risk factors. METHODS: We conducted an observational study on data from a large population of community-dwelling elderly people to tests the hypothesis that the current use of different classes of psychotropic medications, including antipsychotic agents, benzodiazepines, nonbenzodiazepine sedative-hypnotics, and antidepressants, increases the risk for falls. We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs (n = 2854). RESULTS: After adjusting for all potential confounders, users of any psychotropic drugs had an increased risk of fall of nearly 47% (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.24-1.74). Similarly, compared with nonusers, users of atypical antipsychotic drugs also had an increased risk of falling at least once (OR, 1.45; 95% CI, 1.00-2.11). Among benzodiazepine users, patients taking agents with long elimination half-life (OR, 1.45; 95% CI, 1.00-2.19) and patients taking benzodiazepines with short elimination half-life (OR, 1.32; 95% CI, 1.02-1.72) had an increased risk of falls. Patients taking antidepressants did not show a higher risk of falling compared to nonusers (OR, 0.92; 95% CI, 0.83-1.41). CONCLUSIONS: Our data suggest that, among psychotropic medications, antipsychotic agents and benzodiazepines are associated with an increased risk of falls. Our findings do not support the hypothesis that preferential prescribing of short-acting benzodiazepines instead of long-acting agents or atypical antipsychotic medications instead of typical agents will substantially decrease fall risk associated with the use of these classes of drugs.     

Barriers and incentives for Italian paediatricians to become smoking cessation promoters: a GARD-Italy Demonstration Project

BackgroundPaediatricians rarely devote any time to screening and treatment for parental tobacco use. The present project is part of a Global Alliance against Chronic Respiratory Diseases (GARD)-Italy Demonstration Project, aimed to increase the skills of primary care physicians and paediatricians as “promoter of smoking cessation”. The aims of this study were: (I) to identify latent classes of barriers and incentives for smoking cessation counseling among paediatricians using latent class analysis (LCA); (II) to investigate risk factors for inclusion into the identified classes.MethodsIn 2018, 1,500 Italian paediatricians were invited to complete an online survey on passive smoke exposure in children. LCA was used to discover underlying response patterns, and to identify respondent groups with similar attitudes toward passive smoke exposure in children. Multinomial logistic regression helped investigate which explanatory variables influenced inclusion into a class. A P value <0.05 was considered significant.ResultsThe overall response rate was 71% (n=1,071/1,500). Three classes were identified: Class 1 “passive” (n=226, 21.10%); Class 2 “unmotivated” (n=124, 11.58%); and Class 3 “proactive” (n=721, 67.32%). Assuming Class 3 as reference, ever having been a smoker was borderline associated (P=0.052) with increased probability of inclusion into Class 1 (OR =1.43, 95% CI, 1.00–2.06). Having 6–15 or ≥15 years of work experience versus having less than five years was associated with decreased probability of being in the “passive” class (OR =0.46, 95% CI, 0.22–0.96 and OR =0.49, 95% CI, 0.27–0.87, respectively), as was discussing parents’ addiction to alcohol/drugs (OR =0.50, 95% CI, 0.33–0.76).ConclusionsWe identified three profiles among Italian paediatricians related to barriers and incentives for smoking cessation promotion. Tailored educational interventions for paediatricians are required to promote smoking cessation programs.     

Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium

Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM cases and 2465 controls and found a statistically significant (P = 0·0022) association between rs2456449 and MM risk. These data provide further evidence that the genetic variability in the 8q24 region is associated with cancer risk, particularly haematological malignancies.     

Nano-topography: Quicksand for cell cycle progression?

The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells.     

Using imputed genotype data in the joint score tests for genetic association and gene–environment interactions in case‐control studies

Genome‐wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene–environment interactions. We focus on case‐control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene–environment independence in the underlying population. As increasingly large‐scale GWAS are being performed through consortia effort where it is preferable to share only summary‐level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta‐analysis of “one‐step” maximum‐likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type‐I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene–environment interactions under the assumption of gene–environment independence. Methods are made available for public use through CGEN R software package.     

Proctocolectomy and stapled ileo-anal anastomosis without mucosal proctectomy

The present study compared the outcome of a small series of patients (7 cases) who underwent total proctocolectomy without mucosal proctectomy and stapled ileal pouch-anal anastomosis made at the apex of the anal transitional zone, with our previous experience (17 cases) in which the ileal pouch was anastomosed at the dentate line after mucosectomy. Though not statistically significant, our limited experience showed excellent clinical results with better continence and discriminating ability of flatus from faeces in the former group. The resting anal pressure profile was not changed postoperatively. The operation time was significantly reduced compared with our previous approach which was a time-consuming procedure. There was an indication that risk of complications (pelvic sepsis and haemorrhage) was less.