DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Polypharmacy and the use of medications in inpatients with acquired brain injury during post-acute rehabilitation: A cross-sectional study

Background: This study assessed the use of medications during inpatient post-acute rehabilitation for acquired brain injury (ABI).Materials and methods: All inpatients with ABI undergoing post-acute rehabilitation in centres identified through the roster of the Italian Society for Rehabilitation Medicine were included. A designated physician in each centre collected information through a structured questionnaire. This study calculated (a) prevalence of medication use, (b) logistic regression Odds Ratio (OR), with 95% confidence interval (95% CI), of polypharmacy ( 65 6 medications).Results: A total of 484 patients (median age = 52 years, 63.4% men, median time from acute event = 18.5 weeks) were included; 33.8% had Rancho Los Amigos Levels of Cognitive Functioning Scale (RLAS) score 1-2, 8.1% had a score of 7-8, of whom 92.0% received medications, 51.8% had a score of 6-10, of whom 83.9% had at least one psychotropic medication and 66.9% had two or more; 51.8% received anti-epileptics, 32.1% anti-depressants, 14.5% anti-psychotics, peaking in RLAS 4 (37.3%) and decreasing in RLAS 7-8. Polypharmacy was directly associated with age (55-64 years, OR = 2.1; 95% CI = 1.1-4.1; 65 65 years, OR = 1.7; 95% CI = 0.9-3.3), inversely with RLAS score (1-2 vs 7-8, OR = 4.3; 95% CI = 1.9-9.8).Conclusion: Polypharmacy and concurrent use of psychotropic medications was common, raising concern about drug-drug interactions. Safety and effectiveness of medications should be monitored, particularly when used concurrently

Sensitivity of conventional cognitive tests in multiple sclerosis: Application of item response theory

Background: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach. Methods: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results. Results: Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC. Conclusions: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed

Polypharmacy and the use of medications in inpatients with acquired brain injury during post-acute rehabilitation: A cross-sectional study

<p><i>Background</i>: This study assessed the use of medications during inpatient post-acute rehabilitation for acquired brain injury (ABI).</p> <p><i>Materials and methods</i>: All inpatients with ABI undergoing post-acute rehabilitation in centres identified through the roster of the Italian Society for Rehabilitation Medicine were included. A designated physician in each centre collected information through a structured questionnaire. This study calculated (a) prevalence of medication use, (b) logistic regression Odds Ratio (OR), with 95% confidence interval (95% CI), of polypharmacy (≥ 6 medications).</p> <p><i>Results</i>: A total of 484 patients (median age = 52 years, 63.4% men, median time from acute event = 18.5 weeks) were included; 33.8% had Rancho Los Amigos Levels of Cognitive Functioning Scale (RLAS) score 1–2, 8.1% had a score of 7–8, of whom 92.0% received medications, 51.8% had a score of 6–10, of whom 83.9% had at least one psychotropic medication and 66.9% had two or more; 51.8% received anti-epileptics, 32.1% anti-depressants, 14.5% anti-psychotics, peaking in RLAS 4 (37.3%) and decreasing in RLAS 7–8. Polypharmacy was directly associated with age (55–64 years, OR = 2.1; 95% CI = 1.1–4.1; ≥ 65 years, OR = 1.7; 95% CI = 0.9–3.3), inversely with RLAS score (1-2 vs 7–8, OR = 4.3; 95% CI = 1.9–9.8).</p> <p><i>Conclusion</i>: Polypharmacy and concurrent use of psychotropic medications was common, raising concern about drug–drug interactions. Safety and effectiveness of medications should be monitored, particularly when used concurrently.</p