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To solve real life problems under uncertainty in Economics, Finance, Energy, Transportation and Logistics, the use of stochastic optimization is widely accepted and appreciated. However, the nature of stochastic programming leads to a conflict between adaptability to reality and tractability. To formulate a multistage stochastic model, two types of formulations are typically adopted: the so-called stage-scenario formulation named also formulation with explicit non-anticipativity constraints and the so-called nodal formulation named also formulation with implicit non-anticipativity constraints. Both of them have advantages and disadvantages. This work aims at helping the scholars and practitioners to understand the two types of notation and, in particular, to reformulate with the nodal formulation a model that was originally defined with the stage-scenario formulation presenting this implementation in the algebraic language GAMS. In addition, this work presents an empirical analysis applying the two formulations both without any further decomposition to perform a fair comparison. In this way, we show that the difficulties to implement the model with the nodal formulation are somehow reworded making the problem tractable without any decomposition algorithm. Still, we remark that in some other applications the stage-scenario formulation could be more helpful to understand the structure of the problem since it allows to relax the non-anticipativity constraints.

Background The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). Methods Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. Results Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2–2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6–6.3) overall and 17.9/100 person-years (95% CI, 5.8–55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. Conclusions These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. Clinical Trials Registration NCT02336139 and NCT02498015.

This paper uses data envelopment analysis (DEA) approach as a nonparametric efficiency analysis tool to preselect efficient assets in large-scale portfolio problems. Thus, we reduce the dimensionality of portfolio problems, considering multiple asset performance criteria in a linear DEA model. We first introduce several reward/risk criteria that are typically used in portfolio literature to identify features of financial returns. Secondly, we suggest some DEA input/output sets for preselecting efficient assets in a large-scale portfolio framework. Then, we evaluate the impact of the preselected assets in different portfolio optimization strategies. In particular, we propose an ex-post empirical analysis based on two alternative datasets: the components of S &P500 and the Fama and French 100 portfolio formed on size and book to market. According to this empirical analysis we observe better performances of the DEA preselection than the classic PCA factor models for large scale portfolio selection problems. Moreover, the proposed model outperform the S &P500 index and the strategy based on the fully diversified portfolio.

Background & Aims Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. Methods REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. Results The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4–89.0) in the short arm and 86/95, 90.5% (95% CI 82.7–95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8–95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0–99.7; difference -8.3%, p = 0.025). Conclusions In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. Lay summary In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. ClinicalTrials.gov Identifier NCT02625909 .

The main goal of a pension fund manager is sustainability. We propose an Asset and Liability Management model structured as a multi-stage stochastic programming problem adopting a discrete scenario tree and a multi-objective function. Among other constraints, we consider the second-order stochastic dominance with respect to a benchmark portfolio. To protect the pension fund from shocks, we test the inclusion of hedge financial contracts in the form of put options and, moreover, we stress the portfolio introducing a new scenario tree contamination technique, namely the nodal contamination. Numerical results show that we can efficiently manage the pension fund satisfying several targets such as liquidity, returns, sponsor’s extraordinary contribution and funding gap. Moreover, we test the sensitivity with respect to put option strikes and to the stochastic dominance constraints. Finally, we demonstrate the effect of the scenario tree contamination.

We analyse an optimal goal-based households’ asset-liability management problem characterised by a real estate target and a retirement goal over a long-term planning horizon. The problem is formulated as a multistage stochastic program and we evaluate the impact of second order stochastic dominance (SSD) constraints on different specifications of a family objective function and with respect to three alternative benchmark policies. We define a stochastic linear program in which the SSD constraints are based on a double stochastic matrix, whose effectiveness in determining the decision maker strategies is studied in a case study developed in the second part of the article. We show that depending on the adopted benchmark policy, SSD constraints even if binding far on the planning horizon, may influence the root node investment decision and affect both the investment and the liability optimal policies. Based on an extended computational study we analyse under which conditions and problem formulation, an SSD condition may also imply first order stochastic dominance (FSD). Finally we analyse the relationship between the specification of a minimum shortfall objective with respect to the goals and the introduced SSD constraints at the terminal horizon.

Zusammenfassung. Die alkoholische Lebererkrankung (ALE) gehört zu den Hauptursachen einer Zirrhose, des primären Leberzellkarzinoms, des akuten und chronischen Leberversagens und ist damit für eine erhebliche Morbidität und Mortalität verantwortlich. Obwohl Alkoholkonsum in mehreren Ländern leicht gesunken ist, ist er weiterhin hoch und steigt in manchen Ländern sogar. Die Pathophysiologie der ALE ist noch unvollständig geklärt, beruht aber zu grossen Teilen auf der direkten toxischen Wirkung des Alkohols selbst oder seines toxischen Hauptmetaboliten Azetaldehyd. Neue mögliche Mechanismen ergeben sich aus genomweiten Assoziationstudien (GWAS). Die Diagnose einer ALE ist relativ einfach durch einige gut etablierte Nachweismethoden. Eine Leberbiopsie wird nur selten benötigt. Die Therapie der ALE ist dagegen schwierig und erfordert zuallererst Alkoholkarenz als entscheidendes Therapieziel. Die Behandlung der alkoholbedingten Zirrhose entspricht weitgehend dem anderer Ätiologien. Die Lebertransplantation ist eine mögliche Option für hochselektierte Patienten mit Leberzirrhose und alkoholischer Hepatitis, wobei die Rückfall-Raten gering und die Prognose mit anderen Indikationen vergleichbar sind. Jedoch sind viele Länder restriktiv darin, Patienten mit ALE auf eine Transplantationswarteliste zu setzen. Insgesamt gibt es wenige Therapieoptionen für die schwerwiegende ALE und bisher haben nur Kortikosteroide bei der alkoholischen Hepatitis einen klaren Nutzen. Angesichts der epidemiologischen Bedeutung der ALE sind die bisherigen wissenschaftlichen und gesellschaftlichen Bemühungen zu ihrer Lösung enttäuschend gewesen und bedürfen einer Revision, um ähnliche Erfolge zu erzielen, wie dies in anderen Feldern der Hepatologie der Fall ist.

OBJECTIVES: The aim of this study is to compare the theoretical incidence of patient-prosthesis mismatch (PPM) in patients undergoing a sutureless or a sutured aortic valve replacement using an exact statistical matching. METHODS: Between May 2012 and March 2016, 65 patients with severe symptomatic aortic stenosis underwent a sutureless aortic valve replacement with the Perceval bioprosthesis in 2 centres. Moreover, 177 aortic valve replacements with conventional sutured bioprosthesis were performed between August 2003 and September 2015. Perceval and sutured patients were 1:1 exactly matched for sex and body surface area (BSA), resulting in 62 couples (sutureless: BSA 1.77 ± 0.16 m2, female 62.9% vs sutured: BSA 1.77 ± 0.15 m2, female 62.9%). RESULTS: After matching, the indexed effective orifice area was 1.50 ± 0.18 cm2/m2 and 0.81 ± 0.19 cm2/m2 in the sutureless and the sutured group, respectively (P < 0.001). No PPM occurred in patients who received a Perceval bioprosthesis (n = 62). In the sutured group (n = 62), 38 patients (61.3%) developed a PPM, which was moderate in 41.9% (n = 26) and severe in 19.4% (n = 12) (P < 0.001). CONCLUSIONS: The indexed effective orifice area of the sutureless group was significantly larger than in the sutured one. The incidence of PPM with the conventional sutured biprosthesis was 61.3%, while it decreases to 0% in the sutureless group. No PPM was reported in the sutureless valve group. Therefore, the Perceval sutureless valve provides larger effective orifice areas compared to the sutured conventional bioprosthesis and could be considered as a good option to reduce the risk of a PPM.

In this paper we develop an analysis of the efficiency of the expansion strategies to be followed to attain the emissions targets established by the European Commission in the Energy Roadmap 2050. A multi-stage investment model in generating and storage capacity from the point of view of a central planner is presented, considering long-term uncertainties in the decision-making process, such as the demand growth and the investment and fuel costs, and short-term variability. To evaluate the wellness of the expansion strategies according to the CO2 emissions generated and the total cost, second-order stochastic dominance constraints are introduced in the model. This approach allows to obtain better expansion strategies enforcing acceptable distributions of CO2 emissions. The numerical study is carried out considering the case of the European power system. The predictions and suggestions made by the European Commission towards 2050 are the basis to define the benchmark solutions, whose outcomes are analysed. The results obtained from this study highlight that a renewable capacity of at least 2900 GW is needed to attain a net zero CO2 emission European power system. The strategy based on carbon capture and storage does not reduce effectively CO2 emissions while it represents an expensive alternative. Including stochastic dominance in the optimization model allows to obtain less expensive alternative expansion strategies with comparatively lower CO2 emissions in the worst scenarios.

This paper considers an extension of the common asset universe of a pension fund to investment certificates. Investment certificates are a class of structured products particularly interesting for their special payoff structures and they are acquiring relevancy in the worldwide markets. In fact, some subclasses of certificates offer loss protection and show high liquidity and, thus, they can be very appreciated by pension fund managers. We consider the problem of a pension fund manager who has to implement an Asset and Liability Management model trying to achieve a long-term sustainability. Therefore, we formulate a multi-stage stochastic programming problem adopting a discrete scenario tree and a multi-objective function. We propose a technique to price highly structured products such as investment certificates on a discrete scenario tree. Finally, we solve the investment problem considering some investment certificate types both in term of payoff structure and protection level, and we test whether they are preferred or not to standard hedging contract such as put options. Moreover, we test the inclusion of first-order and second-order stochastic dominance constraints on multiple stages with respect to a benchmark portfolio. Numerical results show that the portfolio composition reacts to the inclusion of the stochastic dominance constraints, and that the optimal portfolio is efficiently able to reach several targets such as liquidity, returns, sponsor’s extraordinary contribution and funding gap.

We aimed to assess the clinical and echocardiographic characteristics of patients who underwent surgery for degenerative mitral valve prolapse (MVP) in our center, and its relation to outcomes.We enrolled 117 consecutive patients from North-East China with an echocardiographic diagnosis of MVP related mitral regurgitation (MR) between April 2018 and November 2019. A complexity scoring system was used for valve anatomy, and patients were re-evaluated at 3-6 months after surgery.Most patients (57.3%) were 40-59 years old. Ejection fraction was60% in one third, and pulmonary hypertension was present in 64.3% of operated patients. Etiology was myxomatous in 58.9%, with flail as main lesion. Leaflet involvement was posterior in 59.8% patients, anterior in 32.5%, bileaflet in 6%, and commissural in 25.6%. Lesion score was intermediate in50% of patients, and myxomatous lesions scored higher compared to fibroelastic deficiency (FED). Degree of MR left atrial volume and estimated wedge pressure were significantly higher in intermediate and complex lesions. Repair was performed in 93/101 patients (95.8% success rate). No in-hospital major adverse events, nor deaths at follow-up were reported. Residual MR was ≤ mild in 86.7% of patients at follow-up and was associated with FED etiology and complex lesions.Compared to Western countries, in our sample of Chinese population degenerative severe MR occurred in younger patients. The MVP lesion characteristics are similar, can be accurately detected by non-invasive preoperative evaluation, allowing predictable results. Advanced tailored repair techniques allow excellent immediate and short-term results regardless of the underlying complexity.

Background Regional longitudinal left ventricular (LV) dysfunction in patients with mitral regurgitation (MR) due to valve prolapse (MVP) with normal ejection fraction has been recently described, with data pointing at dysfunction of the LV base related to dilatation of the mitral annulus. Purpose To investigate degree and extent of regional LV dysfunction and its mechanisms in patients with MVP and severe acute (MRa, n=27) or chronic (MRc, n=41) MR and no coronary disease, undergoing surgical valve repair with 3 months follow-up (FU); 20 normal subjects were used as controls (N). Methods Speckle-tracking echocardiography was performed pre- (Bas), 1 week (1w) and 4 months (4mo) post-operatively to measure longitudinal global (GLPSS, %), regional (RPSS, %) and segmental (SPSS) peak systolic strain. Maximum and minimum mitral annulus (MA) diameters were measured with 3D echo at Bas. We also evaluated: LV end-diastolic volume index (EDVi, ml/m2); ejection fraction (EF, %); left atrial end-systolic volume index (LAVi, ml/m2); non-invasive pulmonary systolic pressure (PSP, mmHg). Results Risk factors (hypertension, diabetes, atrial fibrillation, smoke and previous stroke) were similar in MRc and MRa. At Bas EDVi was larger by definition in MRc (MRc: 102±21, MRa: 67±10 ml/m2, p Conclusions In patients with MVP and severe MR, there is a specific regional longitudinal dysfunction pattern prevalent at the LV base which may be related to the duration of MR but not to annular dilatation or morphology of the prolapsing leaflets. The dysfunction worsens greatly following acute reduction of preload after surgical repair and is still significant at 4mo FU. Funding Acknowledgement Type of funding source: None

BACKGROUND Hepatitis C virus (HCV) antigen testing is less expensive than quantitative RT-PCR but has lower sensitivity for very low viral loads (VLVL; HCV RNA ≤3,000 IU/ml). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce. METHODS We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing. RESULTS We included 2,533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female gender and HIV coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall 33% of samples with VLVL were reactive by antigen testing. CONCLUSIONS The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST. Methods: D3FEAT is an international open-label study that recruited treatment-naive participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12). Results: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%–96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed. Conclusion: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.

The asset management sector is constantly looking for a reliable investment strategy, which is able to keep its promises. One of the most used approaches is the target volatility strategy that combines a risky asset with a risk-free trying to maintain the portfolio volatility constant over time. Several analyses highlight that such target is fulfilled on average, but in periods of crisis, the portfolio still suffers market’s turmoils. In this paper, the authors introduce an innovative target volatility strategy: the discontinuous target volatility. Such approach turns out to be more conservative in high volatility periods. Moreover, the authors compare the adoption of the VIX Index as a risk measure instead of the classical standard deviation and show whether the former is better than the latter. In the last section, the authors also extend the analysis to remove the risk-free assumption and to include the correlation structure between two risky assets. Empirical results on a wide time span show the capability of the new proposed strategy to enhance the portfolio performance in terms of standard measures and according to stochastic dominance theory.

Multistage stochastic optimization is used to solve many real-life problems where decisions are taken at multiple times. Such problems need the representation of stochastic processes, which are usually approximated by scenario trees. In this article, we implement seven scenario reduction algorithms: three based on random extraction, named Random, and four based on specific distance measures, named Distance-based. Three of the latter are well known in literature while the fourth is a new approach, namely nodal clustering. We compare all the algorithms in terms of computational cost and information cost. The computational cost is measured by the time needed for the reduction, while the information cost is measured by the nested distance between the original and the reduced tree. Moreover, we also formulate and solve a multistage stochastic portfolio selection problem to measure the distance between the optimal solutions and between the optimal objective values of the original and the reduced tree.

Background Regional left ventricular dysfunction in patients with mitral valve prolapse (MVP) and normal ejection fraction has been described by different Authors, and recent data point to a dysfunction (prevalently longitudinal strain) of the myocardium of the LV base secondary to dilatation of the mitral annulus. Purpose To investigate degree and extent of regional LV dysfunction and its mechanisms in patients with MVP, severe regurgitation and normal global systolic function, compared to patients with equivalent degree of regurgitation but functional etiology (FMR). Methods Speckle-tracking echocardiography was performed in 30 controls (N), and in severe primary (MVP, n= 50) or functional (FMR, n= 20) mitral regurgitation, to measure global, regional and segmental longitudinal peak systolic strain (LPSS, %), and time delay of peak maximum strain (TTPd, ms, calculated as time to peak maximum strain - time of aortic valve closure). Maximum and minimum mitral annulus diameters and area were measured with 3D echo. We also evaluated as recommended: LV end-diastolic volume index (EDVi, ml/m2), ejection fraction (EF, %), and left atrial end-systolic volume index (LAESVi, ml/m2) with 2D echo; LV stroke volume index, and non-invasive pulmonary systolic (PSP, mmHg) and diastolic pressures (PDP), mmHg) with Doppler echo. Results Age, heart rate, BSA and systolic blood pressure were similar between groups. Atrial fibrillation was present in 34% of MVP and 71% of FMR patients. LV EF was normal in MVP and reduced in FMR (43 ± 14 % vs N, p Conclusions In patients with MVP, severe regurgitation and normal EF, there is a specific dysfunction pattern of regional LV longitudinal function which appears to be primary and not dependent on the degree of preload increase, mitral annulus dilatation, or localization of the prolapsing scallop.

As a result of epidemic levels of obesity and diabetes mellitus, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) will contribute to increases in the liver-related disease burden in Switzerland. A Markov model was built to quantify fibrosis progression among the NAFLD and NASH populations, and predict disease burden up to 2030. Long-term trending of NAFLD prevalence was based on changes in the prevalence of adult obesity. Published estimates and surveillance data were applied to build and validate the model projections. The prevalence of NAFLD increased up to 2030 in tandem with projected increases in adult obesity. By 2030, there were an estimated 2,234,000 (1,918,000–2,553,000) NAFLD cases, or 24.3% (20.9–27.8%) of the total Swiss population (all ages). Increases in NASH cases were relatively greater than NAFLD cases. Incident cases of advanced liver disease are projected to increase by approximately 40% by 2030, and incident NAFLD liver deaths to increase from 580 deaths in 2018 to 820 deaths in 2030. Continued growth in obesity, in combination with an aging population, will result in increasing number of cases of advanced liver disease and mortality related to NAFLD and NASH. Slowing the growth in obesity and metabolic syndrome, along with future potential therapies, are required to reduce liver disease burden. &nbsp.

Background Bacterial infection is a major cause of morbidity and mortality for persons who inject drugs (PWID). Injection cessation may help abrogate such infections, but maintaining complete cessation is challenging. Limited data exists on the role of reduced injection intensity on invasive bacterial infection risk. We sought to evaluate decreased risk for bacterial infections following cessation and substantive reduction in the injection intensity. Methods Participants were persons in the AIDS Linked to the Intravenous Experience (ALIVE) cohort with initial high-frequency injection drug use (> 1 daily). Pooled logistic regression with generalized estimating equations was used to estimate risk for invasive bacterial infection (pneumonia, endocarditis, or sepsis) among participants achieving complete injection cessation or reduced injection intensity relative to those with sustained high-frequency use. Results Of 2247 study participants with 12,469 paired study visits, complete injection cessation was achieved at 13.5% and reduced injection intensity at 25.5% of study visits. Adjusting for sociodemographics and HIV status, injection cessation was associated with a 54% reduction of bacterial infection at 3 months (odds ratio [OR] 0.46, 95% CI 0.25–0.84) and a 46% reduction at 6 months (OR 0.54, 95% CI 0.36–0.81). Reduced injection intensity was associated with a 36% reduction of infection at 3 months (OR 0.64, 95% CI 0.43–0.96) and a 26% reduction at 6 months (OR 0.74, 95% CI 0.56–0.98). Conclusions Both complete cessation and reduced injection frequency demonstrate substantial benefit in reducing invasive bacterial infection risk among PWID. With high rates of relapse into injection use, targeting sustained reductions in drug use intensity may be a key harm reduction modality for improving clinical outcomes in this population. Electronic supplementary material The online version of this article (10.1186/s12954-019-0312-8) contains supplementary material, which is available to authorized users.

The use and reimbursement of direct-asting antivirals for all HCV-infected patients (regardless of the stage of disease) has been permitted in Switzerland since November 2017. Although at the outset treatment rates were high, they recently dropped dramatically.

BACKGROUND Hepatitis C virus (HCV) infections in Switzerland are mainly related to intravenous drug use. Since 2017, all patients with chronic hepatitis C can be treated with direct-acting antivirals (DAAs) irrespective of fibrosis stage. In March 2019, the Federal Office of Public Health (FOPH) published guidelines for HCV management in people who use drugs. To achieve HCV elimination by 2030, 80% treatment uptake is necessary. AIM To evaluate the benefit of interferon-based and interferon-free HCV treatment in patients on opioid agonist therapy (OAT) and monitor HCV elimination, a 2-year study commissioned by the FOPH and conducted within the Swiss Association for the Medical Management in Substance Users (SAMMSU) cohort was performed. METHODS Since 2014, the SAMMSU cohort has recruited OAT patients from eight different centres throughout Switzerland. In addition to yearly follow up, cross-sectional data were collected at the time-points 1 May 2017, 1 May 2018 and 1 May 2019. HCV treatment uptake, adherence and success, as well as reinfection rates, the effect of early versus late treatment and the efficacy of the “treatment-as-prevention” approach were analysed. RESULTS Between 1 May 2017 and 1 May 2019, the number of patients enrolled into the SAMMSU cohort increased from 623 to 900: 78% were male, the median age was 45 years, 81% had ever used intravenous drugs, 13% were human immunodeficiency virus (HIV) positive and 66% were HCV antibody positive. HCV treatment up to 2012 was exclusively interferon based (maximum 21 patients/year) and since 2016 exclusively interferon free (102 patients in 2017). Treatment success increased from 57% (112/198; interferon based) to 97% (261/268; interferon free) irrespective of cirrhosis or prior non-response to interferon. Simultaneously, treatments became shorter and better tolerated in the interferon-free era, resulting in fewer preterm stops (17% vs 1%) and adherence problems (9% vs 2%). Between 2015 and 2018, the proportion of patients with no/mild fibrosis (F0/F1) at first HCV treatment increased from 0% to 61%. Earlier treatment reduced the duration of infectiousness. Between 1 May 2017 and 1 May 2019, the proportion of chronic hepatitis C patients ever treated increased from 62% (198/321) to 80% (391/490). In parallel, the HCV-RNA prevalence among HCV antibody-positive patients declined from 36% (139/385) to 19% (113/593). The reinfection rate after successful treatment was 2.7/100 person-years. The number of HCV first diagnoses per year decreased from >20 up to 2015 to

Background: The aim of this study is to evaluate demographic, clinical and laboratory features and outcomes of the hybrid cases undergoing beating heart coronary artery bypass grafting. Methods: January 2011 – 2015 in the isolated beating heart coronary bypass performed (n = 54). The cases were retrospectively analyzed with demographic characteristics and used hybrid approaches. After off-pump coronary artery bypass surgery (OPCAB), the cases were followed for following hybrid coronary revascularization (HCR) with multivessel coronary artery disease (MVCAD). Results: Fifty-four consecutive patients underwent elective HCR (n = 7) or OPCAB (n = 47). The cases consisting of 12 female (22.2%), 42 male (77.7%) were found. 54 cases with an average age of 62.51 years (min: 41, max: 86) (13.279 SD) have been observed. There was no any complication in HCR group. Stroke in 2 case (3.7%), hypoxic ischemic encephalopathy (right internal lacunar infarct) and transient ischemic attack (TIA) in two cases (3.7%) were detected. Inpatients mortality ratio was 7.4% with multiple organ failure. Conclusion: HCR is associated with successful results. We believe that OPCAB should be preferred in selected cases with potential high risk morbidity.

The practical adoption of the Solvency II regulatory framework in 2016, together with increasing property and casualty (PC) claims in recent years and an overall reduction of treasury yields across more developed financial markets have profoundly affected traditional risk management approaches by insurance institutions. The adoption of firm-wide risk capital methodologies to monitor the companies’ overall risk exposure has further consolidated the introduction of risk-adjusted performance measures to guide the management medium and long-term strategies. Relying on a dynamic stochastic programming formulation of a 10 year asset-liability management (ALM) problem of a PC company, we analyse in this article the implications on capital allocation and risk-return trade-offs of an optimization problem developed for a global insurance company based on a pair of risk-adjusted return functions. The analysis is relevant for any institutional investor seeking a high risk-adjusted performance as for regulators in their structuring of stress-tests and effective regulatory frameworks. The introduction of the concept of risk capital, or economic capital, in the definition of medium and long term insurance strategies poses a set of modeling and methodological issues tackled in this article. Of particular interest is the study of optimal ALM policies under different assets’ correlation assumptions. From a computational viewpoint it turns out that, depending on the assumed correlation matrix, the stochastic program is linear or of second order conic type. A case study from a real-world company development is presented to highlight the effectiveness of applied stochastic programming in capturing complex risk and return dynamics arising in modern corporate finance and lead to an efficient long-term financial allocation process.

We present an asset-liability management (ALM) model designed to support optimal strategic planning by a defined benefit (DB) occupational pension fund (PF) manager. PF ALM problems are by nature long-term decision problems with stochastic elements affecting both assets and liabilities. Increasingly PFs operating in the second pillar of modern pension systems are subject to mark-to-market accounting standards and constrained to monitor their risk capital exposure over time. The ALM problem is formulated as a multi-stage stochastic program (MSP) with an underlying scenario tree structure in which decision stages are combined with non-decision annual stages aimed at mapping carefully the evolution of PF’s liabilities. We present a case-study of an underfunded PF with an initial liquidity shortage and show how a dynamic policy, relying on a set of specific decision criteria, is able to gain a long-term equilibrium solvency condition over a 20 year horizon.

Takotsubo cardiomyopathy is a reversible cardiomyopathy, which generally developes in menopausal women and is characterized by left ventricle dysfunction with apical ballooning in the absence of coronary artery disease. It is often triggered by a stressful event, and its clinical presentation resembles acute anterior myocardial infarction. This condition is a rare adverse event of cardiac operations, and only a few cases are described in the literature, especially after mitral valve operations. We report the case of a 69-year-old man who underwent aortic valve repair and ascending aorta replacement, followed by pericardial effusion 6 months later, requiring pericardiocentesis resulting in Takotsubo cardiomyopathy.

Investment certificates are securitized derivatives built as a combination of financial instruments. The financial engineering process aims to create new payoff profiles that allow investors to diversify or to hedge the risk of their portfolios. Such instruments are relatively challenging to price, as highlighted in the recent publications for other European markets. The aim of this paper is to analyze whether in the Italian market there are also differences between the quoted price and the estimated price obtained applying a standard pricing approach well known in the literature. In particular, we analyze three representative certificates, belonging to the classes of target coupon certificates and autocallable certificates, that have been most appreciated by the investors during the last years. To evaluate the price, we propose a Monte Carlo approach that computes directly the payoff of the certificates on a set of scenarios for the evolution of the underlying asset. Moreover, studying the payoff profile of the certificates, we investigate and comment on the recent regulatory debate on “complexity”. We show that complexity, the new parameter behind return and risk, should not be necessarily associated with the engineering level of the financial products and that, sometimes, complexity is not associated with risk.

Conventional valves have a sewing ring that reduces the effective orifice area for a given valve size. In patients with small aortic roots, the implantation of a stented conventional prosthesis can be very difficult or may lead to patient-prosthesis mismatch. In the case of the Sorin Perceval sutureless aortic valve, concomitant mitral valve replacement (MVR) is an exclusion criterion because the latter valve's rigid ring may interfere with the self-expandable stent anchorage of the Sorin Perceval sutureless valve, or cause it to become distorted. The case is reported of very small, 77-year-old woman with severe aortic valve stenosis, severe mitral regurgitation and asymmetric hypertrophy of the left ventricle with systolic anterior motion. The patient underwent MVR and concomitant off-label implantation of the Sorin Perceval S sutureless valve due to the extremely small size of the aortic annulus. Echocardiography performed on completion of surgery, at discharge from hospital and at after a four-month follow up, documented a normal mitral prosthesis position and function, a normal aortic prosthesis position, and mild central regurgitation in both valves.

Editorial; International audience

Increasing financial pressure on State controlled pension systems has caused, over the last two decades or so, an unprecedented effort by private pension funds (PFs) and insurance companies to issue new types of retirement vehicles. This article investigates the effects of such widespread phenomenon from the perspective of individual asset liability management. A multistage stochastic programming problem has been formulated with investment opportunities including PFs, unit-linked contracts and variable life annuities. The introduction of a specific risk measure with respect to a desirable retirement income stream and a planning horizon spanning the entire individuals’ working life helps to analyse the implications of observed market dynamics on retirement strategies. We present comparative results focusing on the retirement planning problem for three representative individuals carrying different time horizons but common retirement goals. The results show the benefits over traditional pension accumulation plans of dynamic strategies based on mixed portfolios of retirement products.

The formulation of dynamic stochastic programmes for financial applications generally requires the definition of a risk–reward objective function and a financial stochastic model to represent the uncertainty underlying the decision problem. The solution of the optimization problem and the quality of the resulting strategy will depend critically on the adopted financial model and its consistency with observed market dynamics. We present a recursive scenario approximation approach suitable for financial management problems, leading to a minimal yet sufficient representation of the randomness underlying the decision problem. The method relies on the definition of a benchmark probability space generated through Monte Carlo simulation and the implementation of a scenario reduction scheme. The procedure is tested on an interest rate vector process capturing market and credit risk dynamics in the fixed income market. The collected results show that a limited number of scenarios is sufficient to capture the expos...

The presence of Echinococcus sp. cysts was investigated in 822 sheep, 123 goats and 112,521 cattle from Lombardy region, North Italy. Faecal samples from 40 sheepdogs were also analyzed, with 9 samples containing taeniid eggs (22.5 %), 8 samples being coproantigen-positive (20 %), and one dog from a northern province (Lecco) positively confirmed by PCR. Cystic Echinococcosis (CE) was detected in 0.36 % of sheep and in 0.29 % of cattle in 2004. No goat resulted to be infected. Data from CE patients treated in Lombardy were collected by inspecting hospital discharge records. In 2004, 156 CE-related admissions (62 % male and 38 % female) were reported in Lombardy. Total hospital stay was 1,372 days (1,286 for inpatients, 86 for outpatients). Most patients (72.4 %) were residents in Lombardy and 1.9 % were from Piedmont; the remaining patients were from central and southern Italy. According to acquired data CE resulted hypoendemic in animals in Lombardy. Prevalence rates in humans were higher than expected in this region, usually considered as non-endemic. Assessment of the prevalence of CE in humans remains a difficult, costly, time-consuming and labourintensive task. The present study suggests establishing a National Registry of Cystic Echinococcosis with the aim to highlight regional risk factors and to benefit from its matching both clinical and epidemiological data.

Various methods of cardioplegia administration have been used in cardiac surgery: crystalloid, blood and mixed crystalloid/blood. Each of these types of cardioplegia administration typically needs a different circuit. This may correspond to an increase in cost and the time needed to change the circuit if required. When various modifications are performed on the circuit, this also increases the risk of contamination. In order to simplify the management of differing cardioplegia circuits, we devised one circuit for all solutions in all situations by adding one modification. The ReVerse cardioplegia circuit system is a description of a two-pump cardioplegia circuit which is adaptable to either blood or crystalloid cardioplegia. The change from one mode to another requires a manoeuvre of two clamps, allowing the blood solution to travel through shunt tubing into the apposite pumphead. In our experience the versatility of this circuit is a fast, safe method to administrate all types of cardioplegia solution, saving the space taken up by storing multiple circuits.

BACKGROUND Switzerland recommends individuals who originate from high-prevalence countries to be screened for hepatitis C virus (HCV) infection. However, not all these persons are equally at risk. We thus aimed to describe the number and characteristics of persons with HCV infection born outside of Switzerland. METHODS We compared characteristics of anti-HCV-positive individuals in the Swiss Hepatitis C Cohort Study (SCCS) and of HCV cases reported to the Federal Office of Public Health (FOPH), with those of the general population in Switzerland. Persons who inject drugs (PWID) and persons who do not inject drugs (non-PWID) were compared by age groups for different countries of origin (represented by ≥1% of participants in the SCCS or FOPH). RESULTS We included 4,199 persons from the SCCS and 26,610 cases from the FOPH. Both groups had similar characteristics. In both data sources non-PWID were more frequent in foreign-born than in Swiss-born persons (63% versus 34% in the SCCS). The only subgroup with a clearly higher proportion both in the SCCS and FOPH than in the general population were persons over 60 years from Italy and Spain, with a 3.7- and 2.8-fold increase in the SCCS. These persons were non-PWID (99%), less frequently HIV- and anti-HBc positive and more often female than PWID from Italy and Spain; cirrhosis at enrolment was frequent (31%). Their HCV genotypes were consistent with those observed in elderly non-PWID of their birth countries. In the FOPH a higher proportion than in the general population was also seen for cases from Georgia and Russia. CONCLUSION The identification of subgroups in which HCV infection is particularly frequent might allow for better targeting HCV screening among foreign-born persons in Switzerland and elsewhere.

Conventional valves have a sewing ring that reduces the effective orifice area for a given valve size. In patients with small aortic roots, the implantation of a stented conventional prosthesis can be very difficult or may lead to patient-prosthesis mismatch. In the case of the Sorin Perceval sutureless aortic valve, concomitant mitral valve replacement (MVR) is an exclusion criterion because the latter valve's rigid ring may interfere with the self-expandable stent anchorage of the Sorin Perceval sutureless valve, or cause it to become distorted. The case is reported of very small, 77-year-old woman with severe aortic valve stenosis, severe mitral regurgitation and asymmetric hypertrophy of the left ventricle with systolic anterior motion. The patient underwent MVR and concomitant off-label implantation of the Sorin Perceval S sutureless valve due to the extremely small size of the aortic annulus. Echocardiography performed on completion of surgery, at discharge from hospital and at after a four-month follow up, documented a normal mitral prosthesis position and function, a normal aortic prosthesis position, and mild central regurgitation in both valves.

To solve a decision problem under uncertainty via stochastic programming means to choose or to build a suitable stochastic programming model taking into account the nature of the real-life problem, character of input data, availability of software and computer technology. In applications of multistage stochastic programs additional rather complicated modeling issues come to the fore. They concern the choice of the horizon, stages, methods for generating scenario trees, etc. We shall discuss briefly the ways of selecting horizon and stages in financial applications. In our numerical studies, we focus on alternative choices of stages and their impact on optimal first-stage solutions of bond portfolio optimization problems.