The Abeer Children Dental Anxiety Scale (ACDAS) cross-cultural adaptation and validity of self-report measures in the Malaysian Children Context (MY-ACDAS).

BACKGROUND: The Abeer Children Dental Anxiety Scale (ACDAS) source language was developed and validated in an English-speaking country in the UK to measure dental anxiety among children. The ACDAS also included the child's cognitive assessment, as well as feedback from the parent or the legal guardian and a dental health professional (DHP). This is the first study to validate the application of the ACDAS in Malay or Bahasa Melayu for children aged 6-16 years. AIM: To assess the Malay-translated version of the ACDAS, postadaptation into the local context and validation by the content and construct experts. DESIGN: The English ACDAS was translated into Malay first through forward translation and then through backward translation. The prefinal translated version of the instrument was designed, with the participation of 61 children and 61 parents or legal guardians. Subsequently, a final cross-cultural adaptation of the instrument was then made for another group of participants and evaluated for validity and test-retest reliability among 144 children and 144 parents or legal guardians participating in the self-report feedback process at the Paediatric Dental Clinic, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia. The cross-cultural adaptation of the instrument considered translating to Malaysian national language and adapting to its culture. RESULTS: The Malay-translated ACDAS consisted of 19 items. The translated version of Malaysian-ACDAS (MY-ACDAS) achieved an acceptable agreement between six expert committee members with an internal consistency (Cronbach's alpha value, αconsistency) of 0.839. The test-retest reliability results of all participants support semantic and conceptual equivalence as an accepted construct validity between the children, parents and DHPs across the multicultural Malaysian population. CONCLUSION: The MY-ACDAS is a valid and reliable scale for measuring dental anxiety among Malaysian children.

High 1-h glucose in youths with obesity as marker of prediabetes and cardiovascular risk.

PURPOSE: Testing 1-h glucose (1HG) concentration during oral glucose tolerance test is cost-effective to identify individuals at risk of incident type 2 diabetes. Aim of the study was to define 1HG cutoffs diagnostic of incident impaired glucose tolerance (IGT) in youths with obesity, and to evaluate prevalence and association of cutoffs identified in the cohort and from the literature (133 and 155 mg/dl) to cardiovascular disease (CVD) in a population of youths with obesity. METHODS: This is a longitudinal study of 154 youths to identify 1HG cutoffs, and cross-sectional study of 2295 youths to estimate prevalence of high 1HG and association to CVD. Receiver-operating characteristic curves (ROC) were used to establish 1HG cutoffs, and univariate regression analyses to test association of 1HG to blood pressure, lipids and aminotransferases. RESULTS: ROC analysis identified the 1HG cutoff of 159 mg/dl as having diagnostic accuracy of IGT with area under the ROC 0.82 (95% CI 0.66-0.98), sensitivity 0.86% and specificity 0.79%. In the cross-sectional population, prevalence of high 1HG was 36% and 15% for 133 and 155 mg/dl cutoffs, respectively, and 17% for the 159 mg/dl value. All the examined cutoffs were significantly associated with worse lipid profile, liver function test, reduced insulin sensitivity, secretion and disposition index. CONCLUSION: High 1HG is marker of persistent IGT and increased risk of metabolic abnormalities in youths. The 155 mg/dl cutoff is a convenient estimate in young people but longitudinal studies with retinopathy and overt diabetes as end points are advised to verify the 1HG cutoff with the best diagnostic accuracy.

Multicentric Italian case-control study on 25OH vitamin D levels in children and adolescents with Prader-Willi syndrome.

PURPOSE: 25OHD levels in patients with Prader-Willi Syndrome (PWS), the most frequent cause of genetic obesity with a peculiar fat mass distribution, are still debated. Insulin resistance (IR), Body Mass Index-SDS (BMI-SDS), Growth Hormone Therapy (GHT), and puberty onset seem to interact with 25OHD levels. The objectives of the study are: (1) To analyze 25OHD levels in pediatric PWS patients in comparison with a control group (CNT) (2) To evaluate a possible correlation between BMI-SDS, HOMA-IR, puberty, GHT, and 25OHD levels. METHODS: This is a retrospective case-control, multicenter study. Data were collected among 8 different Italian Hospitals (outpatient clinics), over a period of four years (2016-2020). We included 192 genetically confirmed PWS and 192 CNT patients, aged 3-18 years, matched 1:1 for age, gender, BMI-SDS, Tanner stage, sun exposure, and month of recruitment. RESULTS: No statistically significant differences in 25OHD levels were observed between the PWS population and the CNT (PWS 24.0 ng/mL vs CNT 22.5 ng/mL, p > 0.05), OR = 0.89 (95% CI 0.58-1.35). We observed a slight, although non-significant, reduction in 25OHD levels comparing NW and OB populations. HOMA-IR, puberty onset, genotype and GHT (previous or ongoing) did not show statistically significant correlation with 25OHD levels. CONCLUSIONS: Our findings could be useful for clinicians to optimize the therapeutic management as well as to increase awareness of PWS.

MKRN3 circulating levels in Prader-Willi syndrome: a pilot study.

CONTEXT: Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS. OBJECTIVE: This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI). METHODS: We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years. RESULTS: MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 ± 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007). CONCLUSIONS: The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.

Parathyroid scintigraphy in primary hyperparathyroidism: comparison between double-phase and subtraction techniques and possible affecting factors.

PURPOSE: Parathyroid scintigraphy is superior to other imaging techniques in detecting hyperfunctioning parathyroid glands. It is mainly performed using double-phase or dual-tracer subtraction methods. Neither of the techniques is perfect and different protocols are being used. We aimed to evaluate the accuracy of double-phase and subtraction methods in detecting abnormal gland as well as the potential effects of coexisting thyroid disease and clinical-laboratory data. METHODS: We considered patients with primary hyperparathyroidism who underwent parathyroid surgery, after a parathyroid scintigraphy between April 2015 and February 2017. Sixty-eight patients were included; in 45 cases (66.2%), a thyroid disease was coexistent. Diagnostic performances of the two techniques were compared. The effect of thyroid disease and clinical-pathological data on examination interpretation was considered. RESULTS: Double-phase scintigraphy showed higher sensitivity and accuracy in detecting the exact abnormal gland compared to the digital subtraction (90% and 75% vs. 76% and 66%, respectively). For double-phase technique, sensitivity and accuracy were higher in cases with no thyroid disease when compared to those with thyroid disease (92% and 86% vs. 88% and 69%, respectively). Similarly, for digital subtraction, sensitivity and accuracy were higher in the absence of thyroid disease compared to their presence (84% and 79% vs. 70% and 58%, respectively). There was no significant variation in the performance of both techniques, considering clinical-laboratory data. CONCLUSIONS: Double-phase scintigraphy has been more accurate than digital subtraction. The presence of thyroid disease could be a possible limit, affecting the subtraction more than the double-phase technique. Clinical data did not influence the scintigraphic outcome.

Hybrid atrial fibrillation ablation in patients with persistent atrial fibrillation or failed catheter ablation.

BACKGROUND: Combined 'hybrid' thoracoscopic and percutaneous atrial fibrillation (AF) ablation is a strategy used to treat AF in patients with therapy-resistant symptomatic AF. We aimed to study efficacy and safety of single-stage hybrid AF ablation in patients with symptomatic persistent AF, or paroxysmal AF with failed endocardial ablation, and assess determinants of success and quality of life. METHODS: We included consecutive patients undergoing single-stage hybrid AF ablation. First, we performed epicardial ablation, via thoracoscopic access, to isolate the pulmonary veins and superior caval vein and to create a posterior left atrial box. Thereafter, isolation was assessed endocardially and complementary endocardial ablation was performed, followed by cavotricuspid isthmus ablation. Efficacy was assessed by 12-lead electrocardiography and 72-hour Holter monitoring after 3, 6 and 12 months. Recurrence was defined as AF/atrial flutter/tachycardia recorded by electrocardiography or Holter monitoring lasting >30 s during 1­year follow-up. RESULTS: Fifty patients were included, 57 ± 9 years, 38 (76%) men, 5 (10%) paroxysmal, 34 (68%) persistent and 11 (22%) long-standing persistent AF. At 1­year 38 (76%) maintained sinus rhythm off antiarrhythmic drugs. Majority of recurrences were atrial flutter (9/12 patients). Success was associated with type of AF (p = 0.039). Patients with paroxysmal AF had highest success, patients with longstanding persistent AF had lowest success. Seven (14%) patients had procedure-related complications. Quality of life improved after ablation in patients who maintained sinus rhythm. CONCLUSION: Success of single-stage hybrid AF ablation was 76% off antiarrhythmic drugs, being associated with type of AF. Quality of life improved significantly, Procedure-related complications occurred in 14%.

Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype.

Cornelia de Lange syndrome (CdLS) and KBG syndrome are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, and some craniofacial and limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified in at least 70% of the patients with CdLS. Consequently, additional causative genes, either unknown or responsible of partially merging entities, possibly account for the remaining 30% of the patients. In contrast, KBG has only been associated with mutations in ANKRD11. By exome sequencing we could identify heterozygous loss-of-function mutations in ANKRD11 in two patients with the clinical diagnosis of CdLS. Both patients show features reminiscent of CdLS such as characteristic facies as well as a small head circumference which is not described for KBG syndrome. Patient A, who carries the mutation in a mosaic state, is a 4-year-old girl with features reminiscent of CdLS. Patient B, a 15-year-old boy, shows a complex phenotype which resembled CdLS during infancy, but has developed to a more KBG overlapping phenotype during childhood. These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes.

Fetal growth patterns in Beckwith-Wiedemann syndrome.

We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.

Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction.

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.

Patients undergoing elective coronary artery bypass grafting exhibit poor pre-operative intakes of fruit, vegetables, dietary fibre, fish and vitamin D.

CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 µg/d; range 1.9-11.2 µg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 µg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.

Employee Safety Motivation: perspectives and measures on the basis of the Self-Determination theory.

BACKGROUND: There is a growing body of literature demonstrating that employee's safety behaviour is largely influenced by their motivation to work safely. The Self-Determination Theory, which proposes a multidimensional conceptualization of motivation, is now established in various domains of the academic field (Healthcare, Education, Psychopathology, Organizations, Sport etc.). However, there are few publications concerning its use in the analysis of motivation in a safety context, where it constitutes a new topic of study. OBJECTIVE: The aim of this study was to develop and validate the Italian version of the Self-Determined Safety Motivation Scale and analyze the psychometric properties of the scale in terms of construct validity. METHODS: The research involved 387 Italian employees from three companies, who occupied medium-low levels in the organizational hierarchy. RESULTS: A good level of psychometric properties was shown. CONCLUSION: The Italian version of the Self-Determined Safety Motivation Scale is a reliable and valid instrument to assess safety motivation.

Griffin and Neal's safety model: Determinants and components of individual safety performance in the Italian context.

INTRODUCTION: Griffin and Neal's model is a useful model to understand workers' different safety behaviour (compliance and participation) starting from their mastery of safety procedures (safety knowledge) and the motivation to put them in place (safety motivation). Although the theoretical model has proven to be adequate and is widely used in research, two problems arise: 1) there is no Italian validation of the four scales measuring the key constructs of the model; 2) the hypothesis regarding the differential impact of the determinants on the components of safety performance produced mixed evidence. OBJECTIVES: The study had a twofold objective: 1) validate an Italian version of the four scales, primarily assessing their construct validity; 2) verify the relationships between the constructs according to the assumptions made within the theoretical model. METHODS: The psychometric properties of the scales as well as the relationships between the constructs were investigated in a sample of 277 workers in the construction and logistics sectors, using questionnaires. The analyses were based on the use of structural equation modelling technique. RESULTS: Results confirmed the validity and reliability of the Italian scales, showing indices that were both satisfactory and aligned with those from previous studies. The relationships between the constructs were substantially consistent with the safety model. CONCLUSIONS: The study provided a valid version of the scales measuring determinants and components of individual safe performance. Such scales can be appropriately used in the Italian context for the development of theoretical as well as practical contributions on work safety. The results suggest that interventions to increase overall safe performance should address both knowledge and motivation for safety.

A pilot study of cerebral tissue oxygenation and postoperative cognitive dysfunction among patients undergoing coronary artery bypass grafting randomised to surgery with or without cardiopulmonary bypass*.

Coronary artery bypass surgery, performed with or without cardiopulmonary bypass, is frequently followed by postoperative cognitive decline. Near-infrared spectroscopy is commonly used to assess cerebral tissue oxygenation, especially during cardiac surgery. Recent studies have suggested an association between cerebral desaturation and postoperative cognitive dysfunction. We therefore studied cerebral oxygen desaturation, defined as area under the cerebral oxygenation curve < 40% of > 10 min.%, with respect to cognitive performance at 4 days (early) and 3 months (late) postoperatively, compared with baseline, using a computerised cognitive test battery. We included 60 patients, of mean (SD) age 62.8 (9.4) years, scheduled for elective coronary artery bypass grafting, who were randomly allocated to surgery with or without cardiopulmonary bypass. Cerebral desaturation occurred in only three patients and there was no difference in cerebral oxygenation between the two groups at any time. Among patients who received cardiopulmonary bypass, 18 (62%) had early cognitive decline, compared with 16 (53%) in the group without cardiopulmonary bypass (p = 0.50). Three months after surgery, 11 patients (39%) in the cardiopulmonary bypass group displayed cognitive dysfunction, compared with four (14%) in the non-cardiopulmonary bypass group (p = 0.03). The use of cardiopulmonary bypass was identified as an independent risk factor for the development of late cognitive dysfunction (OR 6.4 (95% CI 1.2-33.0) p = 0.027. In conclusion, although cerebral oxygen desaturation was rare in our population, postoperative cognitive decline was common in both groups, suggesting that factors other than hypoxic neuronal injury are responsible.

Haematopoietic stem cell transplantation: a comparison between the accreditation process performed by competent authorities and JACIE in Italy.

There have been great advances over the last decades in haematopoietic stem cell (HSC) transplantation, using either bone marrow, peripheral blood or cord blood-derived stem cells. The coming into force of the European legislation on tissues and cells and the consequent transposition of Directives into national laws have required the health authorities in the Member States (MS) and the scientific societies to review the transplantation activities to ensure the circulation of safe HSC products. Here, the regulatory inspection process performed by the Competent Authorities and the professional voluntary accreditation process of the Transplant Programmes active in Italy is compared.

Inositol: effects on oocyte quality in patients undergoing ICSI. An open study.

OBJECTIVES: Nuclear and cytoplasmic competence of human oocyte is critical for future competence of the embryo upon which ultimately depends the outcome of an ART (Assisted Reproductive Technology) treatment. Follicular microenvironment in which the oocyte develops is crucial, and this must be taken into account particularly with the use of hormonal ovarian stimulation protocols. Inositol is an important element of the follicular environment and data support that its higher level in follicular fluid correlates with the development of a good oocyte. Aim of this study is to understand the effects of treatment with inositol on oocyte quality in a sample of patients undergoing ICSI (Intracytoplasmic Sperm Injection). PATIENTS AND METHODS: Assessment of oocyte/embryo quality and pregnancy rates in 149 patients divided, according to a controlled randomized pattern, into two groups: study group 1 treated with folic acid and inositol and control group 2 treated with folic acid alone. RESULTS: The number of patients with excellent and good oocyte quality appears to be significantly higher in group 1 (p = 0.02), as shown, they significantly increased the number of embryos of grade A transferred in the group 1 (p = 0.02) compared to group 2, despite being completely similar averages of total embryos transferred (total mean ± SD = 2.4 ± 0.8, group 1 mean ± SD = 2.4 ± 0.8, group 2 mean ± SD = 2.4 ± 0.8). There is not any significant difference between groups 1 and 2 in the number of positivity to ß-hCG and in the number of biochemical pregnancies detected although it has a tendency to increase in the first and to decrease in the second for group 1. The increase in percentage of clinical pregnancies in group 1 was statistically significant (p = 0.02), whereas there was no apparent significance in the difference between the biochemical and clinical pregnancies in the two groups despite the positive trend in the study group. CONCLUSIONS: Relying on "inositol help" to solidify our efforts, seems to be an easy path to help to deepen the effectiveness of its use in all patients still under 40 but with prior failed attempts at ICSI or diagnosed with PCOS or as "poor responders".

Photodegradation of chlorpyrifos in water by UV/H2O2 treatment: toxicity evaluation.

Chlorpyrifos (CP) is an organophosphorus pesticide widely used in agriculture. Due to its toxicity, it has been necessary to develop a treatment to eliminate the environmental wastes generated by this substance. The combination of UV radiation and hydrogen peroxide seemed an interesting option to reduce the concentration of CP in water, as it has proved to be a simple and effective method to degrade other similar pesticides. The purpose of this work is to study the effect of different initial concentrations of H2O2 on the degradation of commercial CP in water using UV/H2O2. Conversions of 93% were achieved in 20 min with 450 mg L(-1) of H2O2 initial concentration (0.16 mg of CP degraded per mg of H2O2 consumed). The total organic carbon analysis showed interesting mineralization values, reaching a 70% conversion after 4 h of reaction. In addition, this degradation procedure leads to a clear reduction of the toxicity of the reaction mixture over Vibrio fischeri.

Real-life experience with ixekizumab in plaque psoriasis: a multi-center, retrospective, 3-year study.

BACKGROUND: Confirmatory data on the long-term effectiveness and safety of ixekizumab in psoriatic patients from real-world studies are needed. OBJECTIVES: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. METHODS: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed and descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered to be of clinical importance. RESULTS: A total of 306 patients were enrolled. The overall drug survival at 12, 24, and 36 months of treatment with ixekizumab was 92.11%, 83.85%, and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). CONCLUSIONS: We found that ixekizumab is a biological agent characterized by long-term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma.

BACKGROUND: We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial. PATIENTS AND METHODS: Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed. RESULTS: Overall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization. CONCLUSIONS: Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing. TRIAL REGISTRATION: ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy.

PURPOSE: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes. MATERIALS AND METHODS: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other. RESULTS: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in timeframes of ≈ 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively. CONCLUSIONS: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients.