RIGHT TO DISCONNECT: FRENCH AND ITALIAN PROPOSALS FOR A GLOBAL ISSUE

In recent years, the increasing process of digitization has gradually blurred the boundaries between work and private life. Therefore, new issues concerning workers’ protection arose. One of the main topics on this matter is related to employees’ tendency to utilize technological devices, as smartphones and tablets, to remain “connected” to their job outside ordinary business hours. In relation to this aspect, the paper addresses the debate and juridical solutions proposed and developed in France, through the Loi El Khomri, and in Italy, with the law No. 81/2017 recently approved by Parliament, to introduce a right (and/or an obligation) to disconnect in favour of digitized employees, and in order to protect workers’ private life, preventing diseases related to risk of burnout and the augmentation of stress. Furthermore, the analysis will be focused on the social debate related to the abovementioned topic. In particular, it will concern the positions assumed on this matter by main workers’ and employers’ organizations of the said countries, and their reactions to the initiatives undertaken by legislators, in order to realize a first evaluation concerning the impact of the solutions proposed. Afterwards, the attention will be cantered on praxis and tools introduced by collective agreements, in order to verify whether social partners have been able to find more efficient methods to balance work and private life, than the ones suggested by legislators. The outcome of the paper is referred to the actions that ILO could assume, on the base of the experience developed in France and in Italy, to address the future global issue of protecting employees’ work-life balance

NEW ITALIAN EFFORTS AGAINST FALSE INDEPENDENT WORK

1. Introduction; 2. From employer-coordinated freelance work agreements to the crisis of project-based work: the evolution of remedies against false independent work; 2.1. Article 409.3 c.p.c. and the first period of employer-coordinated freelance work agreements; 2.2. The project-based work; 2.3. Efforts to reform project-based work; 3. The innovations provided by Legislative Decree n. 81/2015; 4. In particular: the heter-organized work and the reallocation of risk; 5. The effects of introduction of heter-organized work on Italian occupational levels; 6. Implications of heter-organized work with reference to new issues concerning sharing economy; 7. Conclusions.1. Introduction; 2. From employer-coordinated freelance work agreements to the crisis of project-based work: the evolution of remedies against false independent work; 2.1. Article 409.3 c.p.c. and the first period of employer-coordinated freelance work agreements; 2.2. The project-based work; 2.3. Efforts to reform project-based work; 3. The innovations provided by Legislative Decree n. 81/2015; 4. In particular: the heter-organized work and the reallocation of risk; 5. The effects of introduction of heter-organized work on Italian occupational levels; 6. Implications of heter-organized work with reference to new issues concerning sharing economy; 7. Conclusions

Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed. After general disappointment around CVOTs assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1 receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non-fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause mortality. While available mechanistic studies largely support a cardioprotective effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular death was unexpected and deserves future investigation. We herein review the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate CVOT findings into clinical practice

Use and effectiveness of dapagliflozin in routine clinical practice. An Italian multicenter retrospective study

In randomized controlled trials (RCTs), sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to confer glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase-4 inhibitors, gliclazide, or glucagon-like peptide-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose-lowering medications (GLMs), 6751 of whom had a follow-up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real-world study shows an initial channelling of dapagliflozin to difficult-to-treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS)

Simvastatin Rapidly and Reversibly Inhibits Insulin Secretion in Intact Single-Islet Cultures

open10Epidemiological studies suggest that statins may promote the development or exacerbation of diabetes, but whether this occurs through inhibition of insulin secretion is unclear. This lack of understanding is partly due to the cellular models used to explore this phenomenon (cell lines or pooled islets), which are non-physiologic and have limited clinical transferability.openScattolini, Valentina; Luni, Camilla; Zambon, Alessandro; Galvanin, Silvia; Gagliano, Onelia; Ciubotaru, Catalin Dacian; Avogaro, Angelo; Mammano, Fabio; Elvassore, Nicola; Fadini, Gian PaoloScattolini, Valentina; Luni, Camilla; Zambon, Alessandro; Galvanin, Silvia; Gagliano, Onelia; Ciubotaru, CATALIN DACIAN; Avogaro, Angelo; Mammano, Fabio; Elvassore, Nicola; Fadini, GIAN PAOL

Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (-6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (-1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had -17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (-14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies

Mechanisms of cardiovascular protection of non-insulin antidiabetic medications

Patients with type 2 diabetes mellitus die most frequently from cardiovascular disease (CVD). Metabolic control is a cornerstone of both primary and secondary prevention of CVD: its important is two-fold since the normalization of HbA1c not only counteracts the onset, and the progression of microvascular complication, but has also important and positive role in reducing the risk of major adverse cardiovascular events (MACE). However, among the available glucose-lowering medications, some exert a direct CV protection independently from their ability to normalize metabolic control. In this review I will highlight the pathophysiological mechanisms underlying the claimed cardiovascular protection of the different glucose-lowering drugs, the available evidence-based data for their protection, the potential adverse effects, and the different phenotypes of patients eligible for a specific treatment. The knowledge of pathophysiological mechanisms for CV protection of each glucose-lowering medication, and the constraints of their use supports the health care professionals to individualize the normalization of metabolic control in patients with type 2 diabetes mellitus

Update on gene therapy clinical trials for choroideremia and potential experimental therapies

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (−6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (−1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had −17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (−14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies