Application of latent class analysis in assessing the awareness, attitude, practice and satisfaction of paediatricians on sleep disorder management in children in Italy.

AIM: To identify subgroups regarding paediatricians' awareness, attitude, practice and satisfaction about management of Sleep-Disordered Breathing (SDB) in Italy using Latent Class Analysis (LCA). METHODS: A cross-sectional study was conducted on a large sample of Italian paediatricians. Using a self-administered questionnaire, the study collected information on 420 Paediatric Hospital Paediatricians (PHPs) and 594 Family Care Paediatricians (FCPs). LCA was used to discover underlying response patterns, thus allowing identification of respondent groups with similar awareness, attitude, practice and satisfaction. A logistic regression model was used to investigate which independent variables influenced latent class membership. Analyses were performed using R 3.5.2 software. A p-value<0.05 was considered statistically significant. RESULTS: Two classes were identified: Class 1 (n = 368, 36.29%) "Untrained and poorly satisfied" and Class 2 (n = 646, 63.71%) "Trained and satisfied." Involving paediatric pneumologists or otorhinolaryngologists in clinical practice was associated with an increased probability of Class 2 membership (OR = 5.88, 95%CI [2.94-13.19]; OR = 15.95, 95% CI [10.92-23.81] respectively). Examining more than 20 children with SDB during the last month decreased the probability of Class 2 membership (OR = 0.29, 95% CI [0.14-0.61]). FCPs showed a higher probability of Class 2 membership than PHPs (OR = 4.64, 95% CI [3.31-6.55]). CONCLUSIONS: These findings suggest that the LCA approach can provide important information on how education and training could be tailored for different subgroups of paediatricians. In Italy standardized educational interventions improving paediatricians' screening of SDB are needed in order to guarantee efficient management of children with SDB and reduce the burden of disease

Management of Patients Diagnosed with Endometrial Cancer: Comparison of Guidelines

: Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them

Female sexuality and vaginal health across the menopausal age

Objective:The primary aim was to evaluate changes in female sexuality across the menopausal period, and the secondary objective was to test the associations of female sexuality domains with vaginal atrophy and its symptoms.Methods:A cross-sectional multicenter study was performed involving 518 women, 40 to 55 years of age, consulting outpatient gynecological services at 30 centers across Italy. Vaginal atrophy was identified by the contemporaneous presence of a pH >5, subjective vaginal dryness, and an objective sign. The relationships between vaginal atrophy and its main symptoms (vaginal dryness and dyspareunia), and Female Sexual Function Index (FSFI) score and its domains (desire, arousal, orgasm, dyspareunia, lubrication, and sexual satisfaction) were analyzed.Results:The prevalence of sexual dysfunction, as defined by a FSFI score <26.55, was 70.6%, increasing from 55% in the years 40 to 45, to 82.8% (P<0.01) in the years 52 to 55 of age. Mean FSFI score decreased from 40 to 45, to 46 to 48 years of age (23.13\ub19.76 vs 19.49\ub19.88; P<0.05), and from 48 to 51, to 52 to 55 years of age (21.3\ub18.06 to 17.59\ub19.11; P<0.01). Independent determinants of FSFI were age, vaginal atrophy, and the presence of vaginal dryness and dyspareunia (R2 0.208; P=0.011). FSFI score was independently correlated (R2 0.116) with weight (CR -0.067; 95% confidence interval [CI] -0.126, -0.006; P<0.032), menopausal status (CR -2.406; 95% CI -4.180, -0.63; P<0.008), and vaginal dryness (CR -5.647; 95% CI -7.677, -3.618; P<0.0001). Vaginal dryness was the only variable correlated independently with each FSFI domain, including desire (also correlated with menopausal status), arousal (with age and menopausal status), lubrication (with age), orgasm (with age), satisfaction (with vaginal atrophy and being an ex-smoker), and dyspareunia (with age and spontaneously referred dyspareunia).Conclusions:In the perimenopausal years, FSFI score decreases and sexual dysfunction increases by about 30%. Vaginal dryness is the symptom of vaginal atrophy most closely related to all domains of female sexuality

Collateral sensitivity to novel folate cycle inhibitors enhances cisplatin effectiveness against human ovarian cancer cells.

Presentazione della prima evidenza del binding dei peptidi inibitori della Timidilato sintasi all'interfaccia del dimmelo della Proteina

A UHPLC-MS/MS method for the quantification of direct antiviral agents simeprevir, daclatasvir, ledipasvir, sofosbuvir/GS-331007, dasabuvir, ombitasvir and paritaprevir, together with ritonavir, in human plasma

To date, the new standard for treatment of chronic hepatitis C is based on the administration of novel direct acting antivirals. Among these, sofosbuvir, simeprevir, daclatasvir, ledipasvir, dasabuvir, ombitasvir and paritaprevir already entered the clinical use. Anyway, since few pharmacokinetic studies have been conducted on these drugs in a "real life" context poor knowledge is available about their optimal therapeutic range. Without this background, therapeutic drug monitoring is not applicable for treatment optimization. Up to now, a few methods are reported to quantify these drugs in human plasma, and none of them in a simultaneous way. The aim of this work was to develop and validate a simple, fast and cheap, but still reliable UHPLC-MS/MS method for the quantification of these drugs, feasible for a clinical routine use. Solid phase extraction was performed using HLB C18 96-well plates. Chromatographic separation was performed on a BEH C18 1.7\u3bcm, 2.1mm 750mm column, settled at 50\ub0C, with a gradient run of two mobile phases: ammonium acetate 5mM (pH 9.5) and acetonitrile, with a flow rate of 0.4mL/min for 5min. Tandem-mass detection was carried out in positive electrospray ionization mode. Both inter and intraday imprecision and inaccuracy were below 15%, as required by FDA guidelines, while both recoveries and matrix effects resulted within the acceptance criteria. The method was tested on 80 patients samples with good performance. Being robust, simple and fast and requiring a low plasma volume, this method resulted eligible for a clinical routine use

Collateral sensitivity to novel thymidylate synthase inhibitors correlates with folate cycle enzymes impairment in cisplatin-resistant human ovarian cancer cells

The cytotoxicity of two novel folate cycle inhibitors with quinoxalinic structure, 3-methyl-7-trifluoromethyl-2(R)-[3,4,5-trimethoxyanilino]-quinoxaline (453R) and 3-piperazinilmethyl-2[4(oxymethyl)-phenoxy]quinoxaline (311S), was tested against a panel of both cisplatin(cDDP)-sensitive and -resistant carcinoma cell lines. Interestingly, the cisplatin-resistant human ovarian line, C13 cells, exhibited collateral sensitivity towards the two compounds when compared to its sensitive parental 2008 cells. In this resistant line, which showed elevated expression of the folate cycle enzymes, thymidylate synthase (TS) and dihydrofolate reductase (DHFR), due to cisplatin-resistance phenotype, collateral sensitivity correlated with the greater reduction of enzyme expression. In addition, TS and DHFR expression of the other resistant lines, the human ovarian carcinoma A2780/CP cells and the human breast cancer MDA/CH cells, were decreased in accordance with the similar sensitivity or the low level of cross-resistance to these compounds in comparison to their respective parental lines. Noteworthy, unlike 5-fluorouracil, both drugs reduced the level of TS without inducing ternary complex formation with the co-substrate and the nucleotide analogue. Median effect analysis of the interactive effects of cisplatin with the two quinoxalines mainly showed additive or synergistic cell killing, depending on schedules of drug combinations. In particular, synergistic effects were more often obtained, even on the resistant cells, when cisplatin was added at the beginning of the treatment. These results indicate that, despite the possibility of other mechanisms being involved, inhibition of TS cycle enzymes plays an important role in the pharmacology of these compounds, which might also represent a useful component in drug treatment protocols against cDDP-resistant cells