Ten Years of Medical Informatics and Standards Support for Clinical Research in an Infectious Diseases Network

Background It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. Objectives The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. Methods The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. Results Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. Conclusion The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: different effects in different patients populations. Results from a large observational study

Tenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a large cohort of HIV-1 infected patients

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/ emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: Different effects in patients with or without baseline hypercholesterolemia

open10noTenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this retrospective multicentre study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a cohort of HIV-1 infected patients. Total cholesterol (TC), high density lipoproteins (HDL) and low density lipoproteins (LDL) were compared at the moment of the switch and at the first following evaluation, by using paired t-test. Overall, 573 patients were considered, 99% with HIV-RNA <50 copies/ml, with mean age of 49.7 (±0.4) years and median 13.4 (6.9-22.5) years of HIV infection. In the study population with available data (431/573, 75%), mean TC changed from 173 ±1.7 to 188 ±1.8 mg/dl; mean HDL from 46 ±0.7 to 51± 0.7 mg/dl; mean LDL from 111 ±1.5 to 120 ±1.8 mg/dl (p<0.0001 for all). Neither LDL/HDL nor TC/HDL ratio changed significantly, with LDL/HDL from 2.6 ±0.5 to 2.5 ±0.5 (p = 0.12) and TC/HDL from 4.0 ±0.6 to 3.9 ±0.6 (p = 0.11). In patients with baseline diagnosis of hypercholesterolemia (TC>200 mg/dl, N = 87), there was no significant change in TC (224 ±2.2 to 228 ±3.4 mg/dl, p = 0.286) or LDL (150±2.5 to 151±3.2 mg/dl, p = 0.751), while HDL increased from 51 ±1.6 to 55 ±1.7 mg/dl (p<0.0001) and both LDL/HDL and TC/HDL ratio decreased significantly, from 3.2±0.1 to 3.0 ±0.1 (p = 0.025) and from 4.7±0.1 to 4.4 ±0.1 (p = 0.004). In this real life study, a slight increase in lipids was found after switching from RPV/FTC/TDF to RPV/FTC/TAF, but these results were not confirmed in people with hypercholesterolemia, in which lipids did not change and LDL/HDL and TC/HDL ratio decreased.openTaramasso L.; Di Biagio A.; Riccardi N.; Briano F.; Di Filippo E.; Comi L.; Mora S.; Giacomini M.; Gori A.; Maggiolo F.Taramasso, L.; Di Biagio, A.; Riccardi, N.; Briano, F.; Di Filippo, E.; Comi, L.; Mora, S.; Giacomini, M.; Gori, A.; Maggiolo, F

Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort

OBJECTIVES: To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. PATIENTS AND METHODS: In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values. RESULTS: One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25-0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02-0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. CONCLUSIONS: In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections

Ventricular arrhythmias in patients with functional mitral regurgitation and implantable cardiac devices: implications of mitral valve repair with Mitraclip

Background: Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods: We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR) grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results: Ninety-three patients (68.2+/-10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-month follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0+/-17.8 vs. 2.7+/-13.5, P=0.002), sustained VT or ventricular fibrillation (0.9+/-2.5 vs. 0.5+/-2.9, P=0.012) and ICD antitachycardia therapies (2.5+/-12.0 vs. 0.9+/-5.0, P=0.033) were observed. Conclusions: PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort

Weight gain: A possible side effect of all antiretrovirals

Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy