Consumption responses to a large shock to financial wealth: evidence from Italy

We estimate marginal propensities to consume from wealth shocks for Italian households early in the Great Recession. Large asset-price shocks in 2007-2008 underpin instrumental variables. A euro fall in risky financial wealth resulted in cuts in annual total (non-durable) consumption of 8.5-9 (5.5-5.7) cents. We find small effects on food spending. Counterfactuals indicate financial-wealth effects were relatively important for consumption falls in Italy in 2007/08. The estimated effects are consistent with a simulated lifecycle model that captures the wealth shock. Also consistent with the model are findings of stronger wealth effects for agents who were pessimistic about stock returns

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

From 2D leg kinematics to 3D full-body biomechanics-the past, present and future of scientific analysis of maximal instep kick in soccer

Biomechanics investigation on soccer kicking has a relatively long history, yet the body of knowledge is still small. This paper reviews articles published from 1960s to 2011, summarizing relevant findings, research trends and method development. It also discusses challenges faced by the field. The main aim of the paper is to promote soccer kicking studies through discussions on problem solving in the past, method development in the present, and possible research directions for the future

Movement variability and skills monitoring in sports

The aim of this paper was to present a review on the role that movement variability (MV) plays in the analysis of sports movement and in the monitoring of the athlete's skills. MV has been traditionally considered an unwanted noise to be reduced, but recent studies have re-evaluated its role and have tried to understand whether it may contain important information about the neuro-musculo-skeletal organisation. Issues concerning both views of MV, different approaches for analysing it and future perspectives are discussed. Information regarding the nature of the MV is vital in the analysis of sports movements/motor skills, and the way in which these movements are analysed and the MV subsequently quantified is dependent on the movement in question and the issues the researcher is trying to address. In dealing with a number of issues regarding MV, this paper has also raised a number of questions which are still to be addressed

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 < 1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to < 1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

Does Syphilis Increase the Risk of HIV-RNA Elevation >200 Copies/mL in HIV-Positive Patients under Effective Antiretroviral Treatment? Data from the ICONA Cohort

Background:To assess the impact of syphilis infection on the risk of HIV-RNA elevation in people living with HIV (PLWH) with current HIV-RNA ≤50 copies/mL.Setting:The Italian Cohort Naive Antiretrovirals.Methods:All PLWH (2009-2020) under antiretroviral treatment with at least 2 consecutive HIV-RNA values ≤50 copies/mL before the date of syphilis diagnosis and at least 1 HIV-RNA determination after the syphilis event were enrolled. A control group of PLWH without syphilis was matched for mode of HIV transmission. Outcomes were defined using the first HIV-RNA measure in the time window ranging between -2 and +6 months of the diagnosis/index date. The primary outcome used a single value >200 copies/mL to define HIV-RNA elevation associated with risk of transmission. The association between syphilis infection and the protocol defined outcome was evaluated using logistic regression analysis.Results:Nine hundred twenty-six PLWH with a syphilis event were enrolled and matched with a random sample of 1370 PLWH without syphilis. Eighteen of the 926 (1.9%) with syphilis had ≥1 HIV-RNA >200 copies/mL in the window vs. 29/1370 (2.1%) of the not exposed (P = 0.77). In the multivariable analysis adjusted for age, year of diagnosis/index date, and clinical site, syphilis infection was not associated with the risk of HIV-RNA >200 copies/mL (adjusted odds ratio 0.81; 95% confidence interval 0.43-1.52, P = 0.508).Conclusions:We did not find any evidence for an association between syphilis infection and viral elevation >200 copies/mL

Effectiveness of dolutegravir-based vs boosted darunavir-based first-line 3-drug regimens in people with HIV with advanced disease: A trial emulation

Background: No randomized comparisons exist between dolutegravir (DTG) and boosted-darunavir (DRV/b) for people initiating treatment with advanced HIV. Methods: Antiretroviral therapy (ART)-naïve people with HIV (PWH) with CD4 < 200 cells/mm3 or AIDS who started a first-line three-drug regimen with DTG or DRV/b were included. The primary outcome was a composite endpoint of newly diagnosed AIDS, serious non-AIDS events (SNAE), death, virological failure (VF), or discontinuation of the anchor drug due to failure or toxicity. A marginal structural Cox regression model was used to estimate the effect of starting DTG vs DRV/b-based regimens. Results: A total of 1323 advanced ART-naïve PWH were included, 895 starting DTG and 428 DRV/b. The unweighted risks of the composite endpoint by 48 months were 21.1% (95% CI: 18.1; 24.1%) for DTG vs 37.9% (95% CI: 32.7; 43.2%) for DRV/b (P < 0.001). First-line treatment with DTG showed a lower risk of experiencing the composite endpoint than DRV/b (wHR of DTG vs DRV/b 0.47, 95% CI: 0.35; 0.64, P < 0.001). Conclusion: Under the stated assumptions, this analysis indicates that in ART-naïve PWH with advanced disease, ART initiation with DTG vs DRV/b-based regimens leads to a 50% reduction in the risk of AIDS/SNAE/death/VF/discontinuation. This observed difference is partly explained by discontinuation of the anchor drug

Effectiveness and predictors of treatment discontinuation of long-acting cabotegravir/rilpivirine in virologically suppressed people with HIV: real-life data from the Icona Cohort

Background: Phase 3 studies have shown long-acting (LA) cabotegravir/rilpivirine to be effective and tolerable as maintenance therapy in people with HIV (PWH). However, real-life data on their effectiveness are limited. Methods: All PWH enrolled in the Icona Cohort who started LA cabotegravir/rilpivirine with HIV-RNA < 50 copies/mL were included. Times to treatment discontinuation (TD) and to virological failure (VF50, two consecutive HIV-RNA >50 copies/mL or one >1000 copies/mL followed by ART switch) were estimated by the Kaplan–Meier method. Cox regression models, adjusted for age, sex and mode of HIV transmission and stratified by the centre, were employed. Results: Overall, 583 PWH started LA cabotegravir/rilpivirine. Six VF50 were observed, with a 1 year estimated cumulative probability of virological failure of 1.2% (95% CI, 0.5%–3.0%). Resistance-associated mutations for rilpivirine and cabotegravir were detected in 3/4 and 4/4 participants with VF50, respectively, for which the genotypic resistance test was performed. The 1 year cumulative probability of TD was 11.4% (95% CI, 8.6%–14.9%), mainly caused by toxicity/adverse events (73.2%). Multivariable analysis identified heterosexual intercourse and IV drug use as significant risk factors for TD compared with MSM. Conclusions: This analysis demonstrated the short-term effectiveness of cabotegravir/rilpivirine in a real-life setting showing minimal incidence of virological failure but a notable probability of discontinuation due to toxicity or adverse events