Costo-Efficacia di cabozantinib nel trattamento di seconda linea del tumore a cellule renali metastatico (mRCC) in Italia:

Introduction: Renal cell carcinoma (RCC) is the most common form of kidney cancer with >30% already metastatic at diagnosis. For patients who fail tyrosine kinase inhibitor (TKI) therapy, the Italian Medical Oncology Association recommends (level IA) nivolumab and cabozantinib. The aim of this study was to compare the cost-effectiveness of cabozantinib with nivolumab for treatment of adult patients with mRCC following prior TKI therapy in Italy. Methods: A partitioned survival (area under the curve) model was developed for the Italian medical environment. Cost-effectiveness was assessed from the Italian National Healthcare Service (SSN) perspective over a 30-year time horizon (annual discount: 3% rate). In the absence of head-to-head studies, clinical evidence was based on results of network meta-analysis. Health-state-related utilities were informed by EQ-5D data from the METEOR study. Resource use and costs were obtained from published sources. Results: Treatment with cabozantinib dominates nivolumab across a 30-years time horizon. In the reference case, treatment with cabozantinib results in an incremental 0.268 quality-adjusted life years (QALY) and an incremental 0.349 life years (LY) gained with a total saving, for the Italian SSN, of €5,605 compared to nivolumab over 30 years. Cabozantinib is associated with gains in quality adjusted life years versus nivolumab, in all analyses. Results were shown to be sensitive to drug prices variation and robust when altering other parameters. Discussion: Cabozantinib represents an efficient option in the management of mRCC after initial TKI-therapy in Italy. Drug prices impact final results, and this must be carefully considered, especially considering the confidential discounts and outcome/financial-based agreements currently in place in Italy

Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study

The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967–2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5–16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2–7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2–3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2–10.0) and premature delivery (3.5, 1.2–10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

White Matter Microstructure Predicts Autistic Traits in Attention-Deficit/Hyperactivity Disorder

Traits of autism spectrum disorder (ASD) in children with attention-deficit/hyperactivity disorder (ADHD) have previously been found to index clinical severity. This study examined the association of ASD traits with diffusion parameters in adolescent males with ADHD (n = 17), and also compared WM microstructure relative to controls (n = 17). Significant associations (p < 0.05, corrected) were found between fractional anisotropy/radial diffusivity and ASD trait severity (positive and negative correlations respectively), mostly in the right posterior limb of the internal capsule/corticospinal tract, right cerebellar peduncle and the midbrain. No case–control differences were found for the diffusion parameters investigated. This is the first report of a WM microstructural signature of autistic traits in ADHD. Thus, even in the absence of full disorder, ASD traits may index a distinctive underlying neurobiology in ADHD

Mortality among married older adults in the suburbs of Beirut: estimates from offspring data

OBJECTIVE: Countries in transition are characterized generally by poor statistical infrastructures and a dearth of vital information. In this study we use offspring data to examine mortality trends in married older men and women through a multipurpose household survey conducted in 2002 in the suburbs of Beirut, Lebanon. The country had been ravaged by war for almost 16 years. METHODS: A random sample of 1520 respondents, with either or both parents surviving their 65th birthday, provided information on 1172 fathers and 1108 mothers. Age- and sex-specific mortality rates per 1000 person-years were estimated. Using log-linear Poisson regression, mortality risk was examined for three birth cohorts: those reaching age 65 before (pre-1975), during (1975-1990) and after (post-1990) hostilities in the country. FINDINGS: A total of 1037 parental deaths were reported, yielding an overall mortality rate of 48.7 per 1000 person-years (51.4 among males and 45.3 among females). Compared to the pre-1975 cohort, older adults reaching age 65 during the war years, 1975-1990, had the highest mortality risk for both males (rate ratio, RR = 1.48, 95% confidence intervals, CI = 1.07-2.04) and females (RR = 1.22, 95% CI = 0.95-1.58). Mortality risk was significantly higher in males than females, a gender differential notably largest in the 1975-1990 cohort. CONCLUSION: This is the first population-based study in Lebanon to quantify patterns of mortality in cohorts of married older adults. The results suggest that the hostilities may have contributed to decreased survival, particularly among males. The approach used in the study presents a viable option for testing in larger surveys and population censuses in countries that lack reliable statistical infrastructures

Mortality among married older adults in the suburbs of Beirut: estimates from offspring data

OBJECTIVE: Countries in transition are characterized generally by poor statistical infrastructures and a dearth of vital information. In this study we use offspring data to examine mortality trends in married older men and women through a multipurpose household survey conducted in 2002 in the suburbs of Beirut, Lebanon. The country had been ravaged by war for almost 16 years. METHODS: A random sample of 1520 respondents, with either or both parents surviving their 65th birthday, provided information on 1172 fathers and 1108 mothers. Age- and sex-specific mortality rates per 1000 person-years were estimated. Using log-linear Poisson regression, mortality risk was examined for three birth cohorts: those reaching age 65 before (pre-1975), during (1975-1990) and after (post-1990) hostilities in the country. FINDINGS: A total of 1037 parental deaths were reported, yielding an overall mortality rate of 48.7 per 1000 person-years (51.4 among males and 45.3 among females). Compared to the pre-1975 cohort, older adults reaching age 65 during the war years, 1975-1990, had the highest mortality risk for both males (rate ratio, RR = 1.48, 95% confidence intervals, CI = 1.07-2.04) and females (RR = 1.22, 95% CI = 0.95-1.58). Mortality risk was significantly higher in males than females, a gender differential notably largest in the 1975-1990 cohort. CONCLUSION: This is the first population-based study in Lebanon to quantify patterns of mortality in cohorts of married older adults. The results suggest that the hostilities may have contributed to decreased survival, particularly among males. The approach used in the study presents a viable option for testing in larger surveys and population censuses in countries that lack reliable statistical infrastructures