Statins and non-alcoholic fatty liver disease

Dear Editor, In April 9 issue, van den Berg et al1 report interesting results on the indication for lipid‐lowering treatment in a large cohort with suspected non‐alcoholic fatty liver disease (NAFLD) within the population‐based Lifelines Cohort Study. Fatty liver index (FLI) ≥60 was used as a proxy of NAFLD and the NAFLD fibrosis score (NFS) to identify the NAFLD patients with suspected advanced fibrosis. Cardiovascular disease (CVD) risk was established by the 2016 European society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias.2 Subjects with FLI ≥ 60 (suspected NAFLD) had an increased 10‐ year predicted cardiovascular risk compared to those with FLI < 60 with an approximately 2 times higher need for statin therapy based on CVD risk prediction and their LDL cholesterol level. Subjects with a FLI ≥ 60 were more likely to be classified with type 2 diabetes, Metabolic Syndrome (MetS), history of CVD and impaired renal function. Interestingly, estimated 10‐year very high cardiovascular risk was approximately 4 times higher in subjects with a NFS > 0.676 compared to those with the absence of advanced fibrosis. Finally, indication for statin treatment was positively associated with a FLI ≥ 60 after controlling for age, sex, current smoking, impaired renal function, and the presence of MetS and its individual components. The above results have an even greater relevance if we consider that all the subjects who were already on statin therapy were subtracted from the analysis. These findings may have an important clinical relevance and emphasize the need for effective treatment with statins in patients with NAFLD. Indeed, accumulating evidence suggests that CVD, rather than liver disease, dictates the outcomes in NAFLD.3 Besides, in most subjects NAFLD constitutes the hepatic component of MetS and numerous patients have atherogenic dyslipidemia. This study further supports the results of a previous study by our group where under prescription of statins in patients with NAFLD was observed.4 In fact, mild liver enzyme elevation remains a concern and despite its proven efficacy and safety,5 statin administration is sometimes limited by the worry about related side effects. Indeed, there is a tendency of general physicians to discourage statin use in patients with baseline elevation of serum liver enzymes and/ or to discontinue medication when minor alterations were appreciated. Of note, in our study, statin under‐use was high also in patients at very high CV risk such as those with a previous CV event. This study by van den Berg et al further stresses the issue of under prescription of statins in people with NAFLD and indication for treatment, based on CV risk class and low‐density lipoprotein cholesterol target according to ESC/EAS guidelines

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Innovative housing policy tools: impact indicators in the NRRP Urban Regeneration Programmes

The topic of indicators as measurers of the effectiveness of urban and housing transformations strongly re-emerge because of the performance approach the funding of the National Recovery and Resilience Plan (NRRP) is based on. Within the NRRP specific programmes, the issue of performance measurability of interventions was managed with the application of different indicators and application methods. The research group had the opportunity to work on the construction of a system of indicators for a national urban regeneration programme, financed within the NRRP. This paper describes the research aimed at the definition of the indicators for evaluating the design proposals applied to the NRRP financed program called PINQuA (Innovative Programme for Housing Quality). The proposed system of indicators proved useful to promote an objective reading of the interventions and to encourage, in the design proposals application, the response to housing quality criteria aimed, among other issues, at improving the cultural condition of the contexts

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p < 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p < 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

How to promote vaccinations: a pilot study in the North-West of Italy

Background: vaccines are one of the greatest medical discoveries. In various countries, pharmacists are authorised to administer vaccines directly in pharmacies; thus, leading to an increase in the immunisation rate and a notable gain in consensus amongst the population. The main objective was to evaluate the opinion of pharmacy customers regarding the proposal to authorise pharmacies to administer vaccines. Results: 85% of the respondents were in favour of the introduction of a vaccinating pharmacist. The data show more positive attitudes to the introduction of this service amongst subjects with an elderly dependant relative (PR = 1,10; p = 0.025). Furthermore, it can be noticed a higher probability of positive attitudes to the establishment of the vaccinating pharmacist amongst those with positive attitudes to vaccines (PR = 1,15; p = 0.039). Moreover, the pharmacist is seen as a reference on the subject of vaccines by only 8% of interviewees. Discussion: The data highlight the particularly positive feedback regarding the subject of pharmacists being authorised to administer vaccines. This service may, however, encounter obstacles such as economic problems and opposition from other health professionals. Materials and methods: Data were gathered through a face-to-face interview by means of questionnaires in eight pharmacies in the north-west of Piedmont (Italy). Descriptive statistics were performed. The comparison between the proportions and average values was performed by χ2 and t-test. The indicator used for the associations was the Prevalence Ratio (PR). The PR was calculated using a modified Poisson regression with robust standard errors. The level of significance was fixed at 0.05; IC at 95%

Cannabis for Medical Use: Analysis of Recent Clinical Trials in View of Current Legislation

Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of industrial origin and the introduction onto the market of inflorescences for medical use mean that medical doctors can now prescribe Cannabis-based medicines in those countries which allow it. Nevertheless, there is still considerable controversy on this topic in the scientific community. In particular, this controversy concerns: the plant species to be used; the pathologies that can be treated and consequently the efficacy and safety of use; the routes of administration; the methods of preparation; the type and dosage of cannabinoids to be used; and, the active molecules of interest. As such, although medical Cannabis has been historically used, the results of currently completed and internationally published studies are inconclusive and often discordant. In light of these considerations, the aim of this work is to analyse the current legislation in countries that allow the use of medical Cannabis, in relation to the impact that this legislation has had on clinical trials. First of all, a literature search has been performed (PubMed and SciFinder) on clinical trials which involved the administration of Cannabis for medical use over the last 3 years. Of the numerous studies extrapolated from the literature, only about 43 reported data on clinical trials on medical Cannabis, with these mainly being performed in Australia, Brazil, Canada, Denmark, Germany, Israel, Netherlands, Switzerland, the United Kingdom and the United States of America. Once the reference countries were identified, an evaluation of the legislation in relation to Cannabis for medical use in each was carried out via the consultation of the pertinent scientific literature, but also of official government documentation and that of local regulatory authorities. This analysis provided us with an overview of the different legislation in these countries and, consequently, allowed us to analyse, with greater awareness, the results of the clinical trials published in the last 3 years in order to obtain general interest indications in the prosecution of scientific research in this area

A generalized Macdonald operator

We present an explicit difference operator diagonalized by the Macdonald polynomials associated with an (arbitrary) admissible pair of irreducible reduced crystallographic root systems. By the duality symmetry, this gives rise to an explicit Pieri formula for the Macdonald polynomials in question. The simplest examples of our construction recover Macdonald's celebrated difference operators and associated Pieri formulas pertaining to the minuscule and quasi-minuscule weights. As further by-products, explicit expansions and Littlewood-Richardson type formulas are obtained for the Macdonald polynomials associated with a special class of small weights.Comment: 11 pages. To appear in Int. Math. Res. Not. IMR

Technological transfer in an industrial sector in crisis. The relationship between universities and the clay brick and roofing tile industry in Italy

Over the last two decades, technological transfer between universities and the clay brick and roofing tile Italian industry has changed profoundly, going from extremely strategic and anticipative experimental research, which produced product innovation, to research restricted to confirming performance levels of products and solutions already successful on the market. To fully grasp the opportunities for the two sectors to work together, context conditions must be developed able to facilitate the relationship and work plans must be drawn up for carrying out research in those market segments which look all set to grow, so as to provide the clay brick and roofing tile industry with a way to overcome its structural weaknesses and the errors of evaluation it currently suffers from