Switch from public to private retail pharmaceutical expenditures: evidence from a time series analysis in Italy

Objectives To analyse trajectories of retail pharmaceutical expenditures from 2010 to 2019 in Italy to investigate whether there was a switch from public to private expenditure, how the composition of private and public expenditure changed, and whether there are correlations with supply/demand variables. Answering these questions is important to assure pharmaceutical care to all citizens in a public health system where expenditure containment is the issue of pharmaceutical policies. Design and setting Time-trend analysis was carried out in the Italian National Health System (NHS), between 2010 and 2019. We considered the following: Public pharmaceutical expenditure with/without direct distribution of drugs, copayments, household out-of-pocket payments for drugs reimbursable/non-reimbursable by the NHS, and for drugs without prescription requirement. Correlations were tested between expenditure items and relevant statistics (Gini coefficient, resident population demographics, ages and categories of physicians, and current expenditure on health). Results The switch feared between public and private pharmaceutical expenditures was not found: Private expenditure increased (average annual per cent change 1.5%; 95% CI 0.3% to 2.6%), but public spending remained stable (-1.0%; 95% CI -3.0% to 1.1%). Single items of expenditure exhibited significant pattern changes over the study period. A switch from public expenditure without direct distribution of drugs (-3.9%) to expenditure with direct distribution was found (+8.4%). Unexpected increases in household out-of-pocket payments for drugs reimbursable by the NHS (+6.1%) and in copayments (+4.9%) were shown. No notable correlations were found. Conclusions This study offers insights into Italian experience that can be applied to other contexts and the results provide policy-makers issues to reflect on. The findings suggest that policies of pharmaceutical-expenditure management may have multiple effects and unexpected combined effects over time that should be considered when they are designed, and suggest that health policies must be adopted with a systematic logic and a broad and unified vision

Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses.

BackgroundImmune-mediated myositis (IMM) in American Quarter Horses (QHs) causes acute muscle atrophy and lymphocytic infiltration of myofibers. Recently, an E321G mutation in a highly conserved region of the myosin heavy chain 1 (MYH1) gene was associated with susceptibility to IMM and nonexertional rhabdomyolysis.ObjectivesTo estimate prevalence of the E321G MYH1 variant in the QH breed and performance subgroups.AnimalsThree-hundred seven elite performance QHs and 146 random registered QH controls.MethodsProspective genetic survey. Elite QHs from barrel racing, cutting, halter, racing, reining, Western Pleasure, and working cow disciplines and randomly selected registered QHs were genotyped for the E321G MYH1 variant and allele frequencies were calculated.ResultsThe E321G MYH1 variant allele frequency was 0.034 ± 0.011 in the general QH population (6.8% of individuals in the breed) and the highest among the reining (0.135 ± 0.040; 24.3% of reiners), working cow (0.085 ± 0.031), and halter (0.080 ± 0.027) performance subgroups. The E321G MYH1 variant was present in cutting (0.044 ± 0.022) and Western Pleasure (0.021 ± 0.015) QHs at lower frequency and was not observed in barrel racing or racing QHs.Conclusions and clinical importanceKnowing that reining and working cow QHs have the highest prevalence of the E321G MYH1 variant and that the variant is more prevalent than the alleles for hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in the general QH population will guide the use of genetic testing for diagnostic and breeding purposes

Neurofibromatosis-1 regulation of neural stem cell proliferation and multilineage differentiation operates through distinct RAS effector pathways

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by impaired function of the neurofibromin RAS regulator. Using a combination of Nf1 genetically engineered mice and pharmacological/genetic inhibition approaches, we report that neurofibromin differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT and RAF/MEK pathways. While PI3K/AKT governs neurofibromin-regulated NSC proliferation, multilineage differentiation is MEK-dependent. Moreover, whereas MEK-regulated multilineage differentiation requires Smad3-induced Jagged-1 expression and Notch activation, MEK/Smad3-regulated Hes1 induction is only responsible for astrocyte and neuronal differentiation. Collectively, these findings establish distinct roles for the RAS effector pathways in regulating brain NSC function

Defective cAMP generation underlies the sensitivity of CNS neurons to neurofibromatosis-1 heterozygosity

Individuals with the Neurofibromatosis-1 (NF1) inherited cancer syndrome exhibit neuronal dysfunction that predominantly affects the central nervous system (CNS). In this report, we demonstrate a unique vulnerability of CNS neurons, but not peripheral nervous system (PNS) neurons, to reduced Nf1 gene expression. Unlike dorsal root ganglion neurons, Nf1 heterozygous (Nf1+/−) hippocampal and retinal ganglion cell (RGC) neurons have decreased growth cone areas and neurite lengths, and increased apoptosis compared to their wild-type counterparts. These abnormal Nf1+/− CNS neuronal phenotypes do not reflect Ras pathway hyperactivation, but rather result from impaired neurofibromin-mediated cAMP generation. In this regard, elevating cAMP levels with forskolin or rolipram treatment, but not MEK or PI3-K inhibition, reverses these abnormalities to wild-type levels in vitro. In addition, Nf1+/− CNS, but not PNS, neurons exhibit increased apoptosis in response to excitotoxic or oxidative stress in vitro. Since children with NF1-associated optic gliomas often develop visual loss and Nf1 genetically-engineered mice with optic glioma exhibit RGC neuronal apoptosis in vivo, we further demonstrate that RGC apoptosis resulting from optic glioma in Nf1 genetically-engineered mice is attenuated by rolipram treatment in vivo. Similar to optic glioma-induced RGC apoptosis, the increased RGC neuronal death in Nf1+/− mice following optic nerve crush injury is also attenuated by rolipram treatment in vivo. Together, these findings establish a distinctive role for neurofibromin in CNS neurons with respect to vulnerability to injury, define a CNS-specific neurofibromin intracellular signaling pathway responsible for neuronal survival, and lay the foundation for future neuroprotective glioma treatment approaches