Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation

Although cellular tumor-suppression mechanisms are widely studied, little is known about mechanisms that act at the level of tissues to suppress the occurrence of aberrant cells in epithelia. We find that ectopic expression of transcription factors that specify cell fates causes abnormal epithelial cysts in Drosophila imaginal discs. Cysts do not form cell autonomously but result from the juxtaposition of two cell populations with divergent fates. Juxtaposition of wild-type and aberrantly specified cells induces enrichment of actomyosin at their entire shared interface, both at adherens junctions as well as along basolateral interfaces. Experimental validation of 3D vertex model simulations demonstrates that enhanced interface contractility is sufficient to explain many morphogenetic behaviors, which depend on cell cluster size. These range from cyst formation by intermediate-sized clusters to segregation of large cell populations by formation of smooth boundaries or apical constriction in small groups of cells. In addition, we find that single cells experiencing lateral interface contractility are eliminated from tissues by apoptosis. Cysts, which disrupt epithelial continuity, form when elimination of single, aberrantly specified cells fails and cells proliferate to intermediate cell cluster sizes. Thus, increased interface contractility functions as error correction mechanism eliminating single aberrant cells from tissues, but failure leads to the formation of large, potentially disease-promoting cysts. Our results provide a novel perspective on morphogenetic mechanisms, which arise from cell-fate heterogeneities within tissues and maintain or disrupt epithelial homeostasis

Endoscopic stenting for colorectal cancer obstruction as a bridge-to-surgery strategy

Background: Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy. Materials and methods: In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options. Results: Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P =.04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P =.33) and DFS (36 in SEMS; 35 in ES, P =.35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P =.04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P =.04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P =.03). At multivariate analysis, no feature retained an independent predictive power. Conclusion: SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients

Safety and efficacy of switching from infliximab biosimilar CT-P13 to infliximab biosimilar SB2 in patients with inflammatory bowel disease

INTRODUCTION: For patients with inflammatory bowel diseases, switching from infliximab originator to biosimilars is effective and safe. Few data on single switch have been published, and data on multiple switches of different infliximab are unavailable. METHODS: A retrospective analysis of patients who switched from CT-P13 to SB2, and of those with multiple switches among different infliximab compounds was conducted. Clinical activity, C reactive protein (CRP), adverse events (AE) and loss of response (LOR) were recorded. RESULTS: Thirty-six patients (26 males, 14 Crohn's disease and 22 ulcerative colitis) were enrolled and followed up for >6 months. All patients switched from CT-P13 to SB2; 12 of them (33.3%) had already switched from reference Infliximab to CT-P13, and for the remaining patients CT-P13 was the first infliximab. The clinical remission rate six months before and three months after SB2-switch was the same (58.3%) and the rate of mild activity varied from 27.8 to 33.3% (P = 0.68); the percentage of patients with normal CRP values passed from 94.4 to 91.7% (P = 1). Two patients (5.5%) had AE and 11 (30.5%) a LOR. At univariate analysis, patients with a single switch had a non-significant risk of LOR during SB2 [odds ratio (OR) = 7.86; 95% confidence interval (CI) 0.87-71, P = 0.06]. SB2-LOR was associated with previous AE under CT-P13 (OR = 9.1, 95% CI 0.82-100, P = 0.07). None of such factors was significant at multivariate analysis. CONCLUSION: Switching from CT-P13 to SB2 seems to be safe and effective either in patients with a single than in those with multiple switches

Minor perpetrators of sexual crimes: personality, coping style, and parental care - Twenty-three Italian cases

In the field of psycho forensics, any sexual behavior that occurs without consent, without, equality, or as a result of coercion is considered to be abusive (AACAP, 1999; Shaw, 2002). In order for sexual behavior to be considered consensual, certain criteria are necessary: comprehension of the nature of the proposal; an understanding of societal standards regarding sexuality; awareness of the potential consequences and alternatives; the presumption that agreement or disagreement will be respected in the same manner; the decision to engage is a voluntary one; and that those involved are mentally competent (AACAP, 1999). Equal relationship refers to situations in which the two people involved possess equal power within the relationship, and neither of the two is controlled or coerced by the other. Coercion refers to situations where one party abuses authority, offers bribes, makes threats, or uses intimidation tactics in order to win the cooperation or obedience of the other. Sexual conduct during adolescence must not be considered deviant if it involves non-coercive interaction between two peers. It is not always easy to demonstrate coercion, though expert testimony evaluations often focus on this critical aspect. At times it is also challenging to determine what age appropriate sexual behavior is, and if the two people involved are, in fact, developmental and/or chronological peers. Studies on the topic hypothesize the inability of the adolescent to recognize the other as different from him or herself, and the difficulties associated with entering into a sexual relationship with another person, where dysfunctional coping strategies are often employed. One pilot study from 2002 revealed that the parents of adolescent sexual offenders most often employ an overprotective-affectionless parenting style (Craissati J, McClurg G, Browne K). “Affectionless control” parenting style is a risk factor for the development of deviant behavior. Comorbidity rates in adolescent sexual offenders are high and involve behavioral disorders, personality disorders, and emotional-affective disorders. One recent study revealed that about two thirds of sexual offenders meet the criteria for personality disorder. Impulsivity is one of the characteristics typical of people who exhibit aberrant and violent behavior (Baltieri D.A., Andrade A.G., 2008). The aim of this study is to evaluate the relationship between personality, parental care, and coping style in adolescent sex offenders. Instruments: Clinical interviews; psychodiagnostic testing (MMPI, Minnesota for Adolescents, A/2; PBI-Parental Bonding Instrument; CISS-Coping Inventory for Stressful Situations; Questionnaire I-R, frustration-aggression by Caprara et al.; and healthcare, psychological, and judicial documentation. The sample studied thus far is comprised of 23 unmarried male adolescents between the ages of 15 and 20 years at the time of the interview. The average age was 17 years ± 1.6 (standard deviation), and almost all subjects were Italian (1 Albanian), and Catholic (1 atheist, and 1 agnostic). All were investigated for perpetrating sexual violence on other minors. The sample was taken from Judicial Juvenile Social Services, which intervenes following the commission of a crime by a minor. Preliminary results have revealed no particular pathologies on the part of the adolescent sexual offenders who were examined by the authors. The type of parenting style they received appears to have been intrusive-overprotective, which did not allow the adolescent to face typical life challenges, thus impeding his ability to develop coping skills. This type of parenting style includes intrusiveness, enmeshment, encouragement of dependence, and cutting the minor off from the outside world