Cost-effectiveness analysis of initial HIV treatment under Italian guidelines

INTRODUCTION: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines. PATIENTS AND METHODS: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients' characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. RESULTS: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (24,526), and TDF/emtricitabine (FTC) + nevirapine (26,416), and TDF + FTC + EFV (26,558); the remaining strategies have an incremental cost-effectiveness ratio (ICER) value varying from 28,000 to 41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario. CONCLUSION: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of 50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients

Insulin Promotes Survival of Amyloid-Beta Oligomers Neuroblastoma Damaged Cells via Caspase 9 Inhibition and Hsp70 Upregulation

Alzheimer's disease (AD) and type 2 diabetes are connected in a way that is still not completely understood, but insulin resistance has been implicated as a risk factor for developing AD. Here we show an evidence that insulin is capable of reducing cytotoxicity induced by Amyloid-beta peptides (A-beta) in its oligomeric form in a dose-dependent manner. By TUNEL and biochemical assays we demonstrate that the recovery of the cell viability is obtained by inhibition of intrinsic apoptotic program, triggered by A-beta and involving caspase 9 and 3 activation. A protective role of insulin on mitochondrial damage is also shown by using Mito-red vital dye. Furthermore, A-beta activates the stress inducible Hsp70 protein in LAN5 cells and an overexpression is detectable after the addition of insulin, suggesting that this major induction is the necessary condition to activate a cell survival program. Together, these results may provide opportunities for the design of preventive and therapeutic strategies against AD

The brain metabolic correlates of the main indices of neuropsychological assessment in Alzheimer’s disease

Background: The study aimed to investigate the relationships between F-18 fluorodeoxyglucose (18F)FDG uptake and neuropsychological assessment in Alzheimer's disease (AD). Methods: We evaluated 116 subjects with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a brain PET/CT with (18F)FDG, cerebrospinal fluid (CSF) assay, mini-mental state examination (MMSE) and further neuropsychological tests: Rey auditory verbal learning test, immediate recall (RAVLT immediate); Rey auditory verbal learning test, delayed recall (RAVLT, delayed); Rey complex figure test, copy (RCFT, copy); Rey complex figure test, delayed recall (RCFT, delayed); Raven's colored progressive matrices (RCPM); phonological word fluency test (PWF) and Stroop test. We performed the statistical analysis by using statistical parametric mapping (SPM12; Wellcome Department of Cognitive Neurology, London, UK). Results: A significant relationship has been reported between (18F)FDG uptake and RAVLT immediate test in Brodmann area (BA)37 and BA22 and with RCFT, copy in BA40, and BA7. We did not find any significant relationships with other tests. Conclusion: In the AD population, brain (18F)FDG uptake is moderately related to the neuropsychological assessment, suggesting a limited impact on statistical data analysis of glucose brain metabolism

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: different effects in different patients populations. Results from a large observational study

Tenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a large cohort of HIV-1 infected patients

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/ emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: Different effects in patients with or without baseline hypercholesterolemia

open10noTenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this retrospective multicentre study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a cohort of HIV-1 infected patients. Total cholesterol (TC), high density lipoproteins (HDL) and low density lipoproteins (LDL) were compared at the moment of the switch and at the first following evaluation, by using paired t-test. Overall, 573 patients were considered, 99% with HIV-RNA <50 copies/ml, with mean age of 49.7 (±0.4) years and median 13.4 (6.9-22.5) years of HIV infection. In the study population with available data (431/573, 75%), mean TC changed from 173 ±1.7 to 188 ±1.8 mg/dl; mean HDL from 46 ±0.7 to 51± 0.7 mg/dl; mean LDL from 111 ±1.5 to 120 ±1.8 mg/dl (p<0.0001 for all). Neither LDL/HDL nor TC/HDL ratio changed significantly, with LDL/HDL from 2.6 ±0.5 to 2.5 ±0.5 (p = 0.12) and TC/HDL from 4.0 ±0.6 to 3.9 ±0.6 (p = 0.11). In patients with baseline diagnosis of hypercholesterolemia (TC>200 mg/dl, N = 87), there was no significant change in TC (224 ±2.2 to 228 ±3.4 mg/dl, p = 0.286) or LDL (150±2.5 to 151±3.2 mg/dl, p = 0.751), while HDL increased from 51 ±1.6 to 55 ±1.7 mg/dl (p<0.0001) and both LDL/HDL and TC/HDL ratio decreased significantly, from 3.2±0.1 to 3.0 ±0.1 (p = 0.025) and from 4.7±0.1 to 4.4 ±0.1 (p = 0.004). In this real life study, a slight increase in lipids was found after switching from RPV/FTC/TDF to RPV/FTC/TAF, but these results were not confirmed in people with hypercholesterolemia, in which lipids did not change and LDL/HDL and TC/HDL ratio decreased.openTaramasso L.; Di Biagio A.; Riccardi N.; Briano F.; Di Filippo E.; Comi L.; Mora S.; Giacomini M.; Gori A.; Maggiolo F.Taramasso, L.; Di Biagio, A.; Riccardi, N.; Briano, F.; Di Filippo, E.; Comi, L.; Mora, S.; Giacomini, M.; Gori, A.; Maggiolo, F

Evolution of temperature, O3, CO, and N2O profiles during the exceptional 2009 Arctic major stratospheric warming as observed by lidar and mm-wave spectroscopy at Thule (76.5°N, 68.8°W), Greenland.

The 2009 Arctic sudden stratospheric warming (SSW) was the most intense event of this kind ever observed. Unique ground-based measurements of middle atmospheric profiles for temperature, O3, CO, and N2O obtained at Thule (76.5°N, 68.8°W), Greenland, in the period January – early March are used to show the evolution of the 2009 SSW in the region of its maximum intensity. The first sign of the SSW was detected at θ~2000 K on January 19, when a rapid decrease in CO mixing ratio took place. The first evidence of a temperature increase was observed at the same level on 22 January, the earliest date on which lidar measurements reached above ~50 km. The warming propagated from the upper to the lower stratosphere in 7 days and the record maximum temperature of 289 K was observed between 1300 and 1500 K potential temperature on 22 January. A strong vortex splitting was associated with the SSW. Stratospheric backward trajectories indicate that airmasses arriving to Thule during the warming peak underwent a rapid compression and an intense adiabatic warming of up to 50 K. The rapid advection of air from the extra-tropics was also occasionally observed to produce elevated values of N2O mixing ratio. Starting from mid-February the temperature profile and the N2O mixing ratio returned to the pre-warming values in the mid and upper stratosphere, indicating the reformation of the vortex at these levels. In late winter, vertical descent from starting altitudes of ~60 km is estimated from CO profiles to be 0.25±0.05 km/day

Ten Years of Medical Informatics and Standards Support for Clinical Research in an Infectious Diseases Network

Background It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. Objectives The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. Methods The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. Results Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. Conclusion The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years

Rs12979860 and rs8099917 single nucleotide polymorphisms of interleukin-28B gene: simultaneous genotyping in Caucasian patients infected with hepatitis C virus

Introduction. Recent studies have demonstrated the role of the interleukin 28B (IL28B) polymorphisms in predicting treatment induced and spontaneous clearance from Hepatitis C virus (HCV) infection, suggesting the possibility of tailored therapy in HCV infected patients. Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) near IL 28B gene on chromosome 19 are strong predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin. This study was aimed at analyzing the co-prevalence of two common and clinically significant SNPs in a cohort of Ligurian patients. Methods. Two SNPs (rs12979860, rs8099917) were genotyped in the IL28B locus from 175 DNA samples collected from HCV- infected consecutive patients in a Laboratory of Liguria Region, northern Italy. A real-time polymerase chain reaction in a Cor- bett Research Termocycler (Rotor Gene 3000A) by fluorescent probes (Fast Set IL 28B©, Arrow Diagnostics) was used for the detection, according to the manufacturer?s instructions. Results. Carriers of rs12979860CT genotype predominated (87/175, 50%), homozygotes for allele C were 68/175 (39%) and the remaining were homozygotes for IFN-resistant allele T (11%). As for the rs8099917 SNP, genotypes were thus distributed: 96/175 (55%) carried the rs8099917 TT genotype, whereas 70/175 (40%) and 9/175 (5%), were heterozygotes or homozygotes for the G allele. The variants rs12979860CC and rs8099917TT were found in 39% and 54% of overall patients with HCV genotype 1, respec- tively. The combined assessment of examined SNPs resulted in three most prevalent genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TG and rs12979860CT/rs8099917TT) with a frequency of 35%, 31% and 18%, respectively. Discussion. Recent findings demonstrated that in carriers of rs12979860CT the determination of additional genotype of rs8099917 SNP could significantly improve the prediction of SVR. In our study cohort carriers of rs12979860CT represented 50% of all patients, who could take advantage with respect to SVR prediction by further determination of the rs8099917 SNP. The simultaneous genotyping of two IL28B SNPs should thus be recommended in HCV infected patients prior to treatment initiation

Aerosol optical depth climatology from the high-resolution MAIAC product over Europe: differences between major European cities and their surrounding environments

The aerosol optical depth (AOD) is a derived measurement useful to investigate the aerosol load and its distribution at different spatio-temporal scales. In this work we use long-term (2000–2021) MAIAC (Multi-Angle Implementation of Atmospheric Correction) retrievals with 1 km resolution to investigate the climatological AOD variability and trends at different scales in Europe: a continental (30–60∘ N, 20∘ W–40∘ E), a regional (100 × 100 km2) and an urban–local scale (3 × 3 km2). The AOD climatology at the continental scale shows the highest values during summer (JJA) and the lowest during winter (DJF) seasons. Regional and urban–local scales are investigated for 21 cities in Europe, including capitals and large urban agglomerations. Analyses show AOD average (550 nm) values between 0.06 and 0.16 at the urban–local scale while also displaying a strong north–south gradient. This gradient corresponds to a similar one in the European background, with higher AOD being located over the Po Valley, the Mediterranean Basin and eastern Europe. Average enhancements of the local with respect to regional AOD of 57 %, 55 %, 39 % and 32 % are found for large metropolitan centers such as Barcelona, Lisbon, Paris and Athens, respectively, suggesting a non-negligible enhancement of the aerosol burden through local emissions. Negative average deviations are observed for other cities, such as Amsterdam (−17 %) and Brussels (−6 %), indicating higher regional background signal and suggesting a heterogeneous aerosol spatial distribution that conceals the urban–local signal. Finally, negative statistically significant AOD trends for the entire European continent are observed. A stronger decrease rate at the regional scale with respect to the local scale occurs for most of the cities under investigation.</p