The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian Families Assisting Older Alzheimer's Disease Patients: Evidence from the Up-Tech Study

Background: The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs. Method: We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables - education, social class, and the availability of a care allowance - and three outcomes - employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers). Results: The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW. Discussion: Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems. � 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis

Tuberous sclerosis complex (TSC), caused by heterozygous mutations in TSC1 or TSC2, frequently results in intractable epilepsy. Here, we made use of an inducible Tsc1-knockout mouse model, allowing us to study electrophysiological and molecular changes of Tsc1-induced epileptogenesis over time. We recorded from pyramidal neurons in the hippocampus and somatosensory cortex (L2/L3) and combined this with an analysis of transcriptome changes during epileptogenesis. Deletion of Tsc1 resulted in hippocampus-specific changes in excitability and adaptation, which emerged before seizure onset and progressed over time. All phenotypes were rescued after early treatment with rapamycin, an mTOR inhibitor. Later in epileptogenesis, we observed a hippocampal increase of excitation-to-inhibition ratio. These cellular changes were accompanied by dramatic transcriptional changes, especially after seizure onset. Most of these changes were rescued upon rapamycin treatment. Of the genes encoding ion channels or belonging to the Gene Ontology term action potential, 27 were differentially expressed just before seizure onset, suggesting a potential driving role in epileptogenesis. Our data highlight the complex changes driving epileptogenesis in TSC, including the changed expression of multiple ion channels. Our study emphasizes inhibition of the TSC/mTOR signaling pathway as a promising therapeutic approach to target epilepsy in patients with TSC

Photoelectron Diffraction Investigation of Strained InGaAs Grown on (001) GaAs

We have performed Soft X-Ray Photoelectron Diffraction measurents, at the Ga3d, As3d and In4d core levels, to study the effects of strain on InGaAs grown on (001) GaAs. Polar and azimuths] scans have been recorded and compared with Single Scattering Cluster Calculations. A good agreement is obtained between theory and experiment indicating that the lattice expands in the growth direction as predicted by the elastic theory

Sex-related differences in prevalence, treatment and outcomes in patients with atrial fibrillation

To analyze sex-related differences about AF prevalence, use of OAC and outcomes focusing on the older age classes. We used administrative data of the Lombardy Region, describing period prevalence, use of OAC and outcomes from 2002 to 2014 for all patients diagnosed with AF. AF prevalence over the 2002\u20132014 period was higher in males than in females (2.7% vs. 2.1%, p < 0.001), increasing with age. From 2003 to 2014, not treated AF patients decreased mostly in males (from 40.3 to 33.7% with respect to 43.7\u201339.8% in females). Age-stratified adjusted logistic regression analysis found that females were more likely treated with OAC when < 65 years in 2003 (OR 1.51, 95% CI 1.35\u20131.69) and in 2014 (OR 1.32, 95% CI 1.13\u20131.53); contrariwise, were less likely treated with OAC when age 65 75 years, in 2003 (OR 0.92, 95% CI 0.86\u20130.98) and in 2014 (OR 0.77, 95% CI 0.72\u20130.81).Adjusted Cox regression analysis confirmed that female AF patients had a higher risk of stroke (HR 1.18, 95% CI 1.14\u20131.21) and a lower risk of major bleeding (HR 0.83, 95% CI 0.80\u20130.86), while, had a lower risk for all-cause death (HR 0.82, 95% CI 0.80\u20130.83). AF prevalence was higher in male than in female patients, while thromboembolic risk was higher in female. Older female patients were under-treated with OAC particularly in recent years. Over long-term follow-up, female had a higher risk of stroke and a lower risk of major bleeding and all-cause death

Impact of Liver Disease on Oral Anticoagulant Prescription and Major Adverse Events in Patients with Atrial Fibrillation

Aims\u2003 Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention are limited. Methods and results\u2003 A retrospective observational population-based cohort study on the administrative health databases of Lombardy region Italy. All AF patients 6540\u2009years admitted to hospital from 2000 to 2018 were considered. Atrial fibrillation and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical codes. Primary study outcomes were stroke, major bleeding, and all-cause death. Among 393\u2009507 AF patients, 16\u2009168 (4.1%) had concomitant LD. Liver disease AF patients were significantly less treated with OAC. Concomitant LD was associated with an increased risk in all the study outcomes [hazard ratio (HR): 1.18, 95% confidence interval (CI): 1.11\u20131.25 for stroke; HR: 1.57, 95% CI: 1.47\u20131.66 for major bleeding; HR: 1.41, 95% CI: 1.39\u20131.44 for all-cause death]. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70\u20130.92), major bleeding (HR: 0.86, 95% CI: 0.74\u20130.99), and all-cause death (HR: 0.77, 95% CI: 0.73\u20130.80), with similar results according to subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375\u20130.472). Conclusion In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant favourable benefit/risk ratio, even in high-risk patient subgroups

RHEB/mTOR hyperactivity causes cortical malformations and epileptic seizures through increased axonal connectivity

Hyperactivation of the mammalian target of rapamycin (mTOR) pathway can cause malformation of cortical development (MCD) with associated epilepsy and intellectual disability (ID) through a yet unknown mechanism. Here, we made use of the recently identified dominant-active mutation in Ras Homolog Enriched in Brain 1 (RHEB), RHEBp.P37L, to gain insight in the mechanism underlying the epilepsy caused by hyperactivation of the mTOR pathway. Focal expression of RHEBp.P37L in mouse somatosensory cortex (SScx) results in an MCD-like phenotype, with increased mTOR signaling, ectopic localization of neurons, and reliable generalized seizures. We show that in this model, the mTOR-dependent seizures are caused by enhanced axonal connectivity, causing hyperexcitability of distally connected neurons. Indeed, blocking axonal vesicle release from the RHEBp.P37L neurons alone completely stopped the seizures and normalized the hyperexcitability of the distally connected neurons. These results provide new evidence of the extent of anatomical and physiological abnormalities caused by mTOR hyperactivity, beyond local malformations, which can lead to generalized epilepsy