Cost-effectiveness profile, organizational implications and patient preferences on the use of exogenous TSH therapy (Thyrogen®) vs. THW in thyroid residue ablation in Italy

BACKGROUND: Radioiodine ablation is an adjuvant procedure used to treat patients with differentiated thyroid cancer. For ablation to be successful, patients must have elevated levels of thyroid stimulating hormone (TSH). This can be achieved by withholding thyroid hormone therapy (endogenous stimulation), or by administration of recombinant human thyroid stimulating hormone (rhTSH; Thyrogen®; exogenous stimulation) to patients in the euthyroid state.AIM: To compare the estimated health benefits, cost and cost-effectiveness of TSH stimulation with and without Thyrogen® in the Italian setting.METHODS: A cost-utility analysis was undertaken to assess the impact of exogenous vs. endogenous TSH stimulation before radioiodine remnant ablation of patients with newly diagnosed, well-differentiated papillary or follicular thyroid cancer who have undergone total or near-total thyroidectomy. A Markov model was developed to simulate treatment costs and health outcomes associated with exogenous and endogenous stimulation in four distinct health states: pre-ablation, ablation, post-ablation, and well/recovery. Treatment was stratified by patients who receive high- and low-activity (30-100 mCi, respectively) in the ablation state. The Italian National Health System perspective was adopted in the base case scenario while the impact of indirect costs was explored in a sensitivity analysis. Costs and quality-adjusted life years (QALY) specific to each health state were estimated, summarized and converted into a corresponding incremental cost-effectiveness ratio (ICER).RESULTS: We calculated a cost-effectiveness ratio of 18,357.18 €/QALY gained whereas the inclusion of indirect cost and accident cost produced reductions of the ICER to € 14,609.51 and € 15,515.26 per QALY, respectively. Finally, all results in the sensitivity analysis are below the lower bound of national and international cost- effective threshold.CONCLUSION: Thyrogen® represents a cost-effective option for patients with differentiated thyroid cancer who underwent total or near-total thyroidectomy in Italy. Our findings are consistent with other cost-utility analyses

L-Arginina e ipertensione in gravidanza

Il ruolo svolto dal sistema L-Arginina-ossido d’azoto (L-Arg-NO) nella genesi dell’ipertensione gestazionale è consolidato da numerosi studi in vitro ed in vivo. Infatti è stato dimostrato che l’inibizione della produzione di NO determina nell’animale da esperimento i medesimi segni e sintomi che si verificano in corso di preeclampsia (1-4). Recentemente la nostra attenzione si è focalizzata sulla capacità della L-Arginina di modificare la storia ostetrica delle donne affette da ipertensione cronica, che come è noto rappresenta un importante fattore di rischio per lo sviluppo di preeclampsia. A questo proposito sono state prese in esame 62 gravide affette da ipertensione preesistente alla gravidanza afferenti all’Ambulatorio di Patologia Ostetrica del Dipartimento Integrato Materno-Infantile dell’Università di Modena. Scopo dello studio è la valutazione della percentuale di conversione in preeclampsia, la quantità complessiva di farmaco antipertensivo utilizzato durante la gravidanza ed inoltre la valutazione dell’effetto della L-Arginina sulla pressione arteriosa misurato tramite Holter-24 ore. Considerando l’outcome materno-fetale, è stato osservato come il gruppo trattato con L-Arginina presenti rispetto al gruppo osservazione un’epoca gestazionale al parto più avanzata (38.1±2.8 vs 36.9±3.7), peso fetale maggiore (3048±741 vs 2933±950) e minor ricorso al taglio cesareo (20.6% vs 27.6%). Inoltre, il gruppo trattato con L-Arginina presenta una minor percentuale di parti al di sotto della 37ª settimana (26.5% vs 34.5%) e minor percentuale di neonati con peso inferiore a 2500 grammi (20.6% vs 24.1%

Implementation of guidelines about women with previous cesarean section through educational/motivational interventions in providers

Objective: The study reports the effect of a quality improvement project with an educational/motivational intervention, in northern Italy on the implementation of the trial of labor after Caesarean Section (CS). Method: A pre-post study design was used. Every birth center (23) of the Emilia-Romagna region was included. Gynecologists' opinion leaders were first trained about CS Italian recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected in 2 periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. Results: A total of 20,496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (p<0.001). The likelihood of VBAC, adjusted for age ≥40, Caucasian, BMI ≥30, previous vaginal delivery, and labor induction, was increased by the intervention of 42% (OR=1.42, 95% CI 1.31-1.54). Neonatal well-being was improved by intervention, indeed neonates requiring resuscitation decreased from 2.1% to 1.6% (p=0.001). Conclusion: Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being

Attitudes of women towards products containing hormones (hormonal contraceptives or hormone therapy): what changes from pre to postmenopause?

To evaluate the actual perceptions of hormonal contraceptives (HC) in women of reproductive age in comparison with similar concerns of postmenopausal women in relation to hormone therapy (HT)

Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study

Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16-50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications

Use of Radium-223 Dichloride in Patients With Osteonecrosis of the Jaw Induced by Zoledronic Acid: Report of 2 Cases.

Bisphosphonates, a group of inorganic pyrophosphate analogues that prevent the loss of bone density, are commonly used in patients with bone metastases; the calcium-mimetic a-emitter radium-223 dichloride (Ra223) is a bone-targeting therapy used in patients with metastatic castration-resistant prostate cancer (mCRPC)-related bone metastases. Both treatments reduce pain and disability; Ra223 is associated with significantly improved overall survival in mCRPC. Patients who receive bisphosphonate therapy are at risk of developing osteonecrosis of the jaw, especially in those who do not undergo an accurate oral evaluation and sanitation before the beginning of therapy, and in patients who present with conditions that facilitate the development of this problem, such as inadequate oral and dental care, lack of prophylactic antimicrobial mouth rinsing, patient comorbidity, or suboptimal suturing after tooth extraction. Although there is possible synergism between bisphosphonates and Ra223 therapy, there is no consensus about the use of Ra223 in patients with previous/current osteonecrosis of the jaw induced by zoledronic acid. However, our experience suggests that Ra223 therapy might not be contraindicated in patients with osteonecrosis of the jaw induced by zoledronic acid if an appropriate multidisciplinary approach is followed, and we report 2 cases of patients with current or previous osteonecrosis of the jaw induced by zoledronic acid, who were treated with Ra223 for mCRPCrelated bone metastases. Multidisciplinary management, including accurate clinical and radiological evaluation before beginning therapy with Ra223, together with oral sanitation and periodic controls during treatment, allowed successful administration of Ra223 while reducing side effects, with absent or minimal worsening of osteonecrosis

Coordination Chemistry of the (eta(6)-p-Cymene)ruthenium(II) Fragment with Bis-, Tris-, andTetrakis(pyrazol-1-yl)borate Ligands: Synthesis, Structural, Electrochemical, and CatalyticDiastereoselective Nitroaldol Reaction Studies

Novel [Ru(eta(6)-p-cymene)(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O complexes (L = bis-, tris-, or tetrakis-pyrazolylborate; X = Cl, N-3, PF6, or CF3SO3) are prepared by treatment of [Ru(eta(6)-p-cymene)Cl-2](2) with poly-(pyrazolyl)borate derivatives [M(L)] (L in general; in detail L = Ph(2)Bp = diphenylbis-(pyrazol-1-yl)borate; L = Tp = hydrotris(pyrazol-1-yl)borate; L = pzTp = tetrakis(pyrazol-1-yl)borate; L = Tp(4Bo) = hydrotris(indazol-1-yl)borate, L = T-p4Bo,T-5Me = (5-methylindazol-1-yl)borate; L = Tp(Bn,4Ph) = hydrotris(3-benzyl-4-phenylpyrazol-1-yl)borate; M = Na, K, or TI) and characterized by analytical and spectral data (IR, ESIMS, H-1 and C-13 NMR). The structures of [Ru(eta(6)-p-cymene)(Ph(2)Bp)Cl] (1) and [Ru(eta(6)-p-cymene)(Tp)Cl] (3) have been established by single-crystal X-ray diffraction analysis. Electrochemical studies allowed comparing the electron-donor characters of Tp and related ligands and estimating the corresponding values of the Lever E-L ligand parameter. The complexes [Ru(eta(6)-p-cymene)-(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O act as catalyst precursors for the diastereoselective nitroaldol reaction of benzaldehyde and nitroethane to the corresponding beta-nitroalkanol (up to 82% yield, at room temperature) with diastereoselectivity toward the formation of the threo isomer

First-trimester prediction model for placental vascular disorders: an observational prospective study

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications

Test-Driven Design of an Active Dual-Polarized Log-Periodic Antenna for the Square Kilometre Array

An active dual-polarized Log-Periodic antenna has been designed to meet the requirements of the low-frequency (50 - 350 MHz) radio telescope of the Square Kilometre Array (SKA). The integration of antenna and low noise amplifier has been conceived in order to achieve a high degree of testability. This aspect has been found to be crucial to obtain a smooth frequency response compatible with the SKA science cases. The design has also been driven by other factors such as the large-volume production (more than 130 000 antennas will be built) and the environmental conditions of the harsh Australian desert. A specific verification approach based on both wideband radiometric spectral and spatial measurements in relevant laboratory and in-situ conditions has been developed. Electromagnetic analyses and experimental results exhibit a very good agreement. In December 2019, this antenna was part of the reference solution for the System Critical Design Review of the SKA

RELATION BETWEEN MATERNAL THROMBOPHILIA AND STILLBIRTH ACCORDING TO CAUSES/ASSOCIATED CONDITIONS OF DEATH

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95\% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95\%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95\% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia