Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era

Objective: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. Methods: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as “non-adherent” if reporting one of the following criteria:<90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. Results: At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on once-daily regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The non-adherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94) and the STR (OR: 0.45, 95% CI: 0.22–0.92) reported lower non-adherence. Efavirenz regimens were also associated with lower non-adherence (OR: 0.42, 95% CI: 0.21–0.83), while atazanavir/ritonavir regimens were associated with higher non-adherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower non-adherence, while a longer time on combined antiretroviral therapy was related to higher non-adherence. Conclusion: In conclusion, older age, higher CD4 cell counts, lower HIV-RNA viral loads, and the use of STR are all related to lower non-adherence. In particular, the use of STR maintains an advantage in improving adherence with respect to other cARTs, even with the availability of new, well-tolerated antiretroviral drugs and drug classes in recent years

Humanities in the undergraduate medical and midwifery curriculum: a descriptive Italian comparative study.

There is an increasing emphasis on humanized care in obstetric and midwifery practice. The goal of this paper is to investigate if and how medical humanities content was present in the undergraduate medical syllabus and how similar or different this is from the undergraduate midwifery program in Italy. A review of the 2017-18 curriculum for Italian Schools of Medicine and of Midwifery was carried out through institutional websites or mailing requests. The following details were collected for each program: the type of humanities content; the academic credits allocated, whether it was taught as a stand-alone (independent) topic or not, and the year(s) of the program when it was provided. Programs were included for 39 Schools of Medicine and 36 Schools of Midwifery. All midwifery schools included at least one subject with humanities content. Five medical schools (12.9) did not appear to have any subjects in this area. Psychology and ethics/bioethics were the most frequently found topics in both disciplines, but, apart from history of medicine, midwifery was much more likely than medicine to include other humanities topics, and especially pedagogy, anthropology, sociology and communication studies, philosophy and cross-cultural studies were rarely or never included in either discipline. A greater breadth of humanities studies was included in midwifery schools. However, their relative importance appears to be low, given the low level of academic credits and lack of presence as independent subjects

Quantitative evaluation of CFTR pre-mRNA splicing dependent on the (TG)mTn poly-variant tract

Genetic analysis in cystic fibrosis (CF) is a difficult task. Within the many causes of variability and uncertainty, a major determinant is poor knowledge of the functional effect of most DNA variants of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. In turn, knowledge of the effect of a CFTR variant has dramatic diagnostic, prognostic and, in the era of CF precision medicine, also therapeutic consequences. One of the most challenging CFTR variants is the (TG)mTn haplotype, which has variable functional effect and controversial clinical consequences. The exact quantification of the anomalous splicing of CFTR exon 10 (in the HGVS name; exon 9 in the legacy name) and, consequently, of the residual wild-type functional CFTR mRNA, should be mandatory in clinical assessment of patients with potentially pathological haplotype of this tract. Here, we present a real time-based assay for the quantification of the proportion of exon 10+/exon 10- CFTR mRNA, starting from nasal brushing. Our assay proved rapid, economic and easy to perform. Specific primers used for this assay are either disclosed or commercially available, allowing any laboratory to easily perform it. A simplified analysis of the data is provided, facilitating the interpretation of the results. This method helps to enhance the comprehension of the genotype- phenotype relationship in CF and CFTR-related disorders (CFTR-RD), crucial for the diagnosis, prognosis and personalized therapy of CF

Work-related stress and well-being in association with epigenetic age acceleration: a Northern Finland Birth Cohort 1966 Study

Recent evidence indicates consistent association of low socioeconomic status with epigenetic age acceleration, measured from DNA methylation. As work characteristics and job stressors are crucial components of socioeconomic status, we investigated their association with various measures of epigenetic age acceleration. The study population included employed and unemployed men and women (n=604) from the Northern Finland Birth Cohort 1966. We investigated the association of job strain, effort-reward imbalance and work characteristics with five biomarkers of epigenetic aging (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPoAm). Our results indicate few significant associations between work stress indicators and epigenetic age acceleration, limited to a range of ±2 years, and smoking recording the highest effect on GrimAge age acceleration biomarker between current and no smokers (median difference 4.73 years (IQR 1.18, 8.41). PhenoAgeAA was associated with job strain active work (β=-1.301 95%CI -2.391, -0.212), slowing aging of less than 1.5 years, and working as white-collar slowed aging six months (GrimAgeAA β=-0.683, 95%CI -1.264, -0.102) when compared to blue collars. Association was found for working for more than 40 hours per week that increased the aging over 1.5 years, (HorvathAA β =2.058 95%CI 0.517,3.599, HannumAA β=1.567, 95%CI 0.415,2.719). The pattern of associations was different between women and men and some of the estimated effects are inconsistent with current literature. Our results provide the first evidence of association of work conditions with epigenetic aging biomarkers. However, further epidemiological research is needed to fully understand how work-related stress affects epigenetic age acceleration in men and women in different societies

Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction

Local epidemics gone viral: Evolution and diffusion of the Italian HIV-1 recombinant form CRF60_BC

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy

A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events

Background: Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. Results: Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). Conclusions: We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures