SummaryBackgroundThe effect of direct‐acting anti‐virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies.AimTo summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection.MethodsWe performed a systematic review and meta‐analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post‐treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post‐treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman‐Tukey double arcsine transformation. Random effects model was used for all analyses.ResultsAmong 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post‐treatment week 12 was 100% (95% confidence interval: 100‐100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon.ConclusionsChildren and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.

BACKGROUND:Temporal lobe epilepsy (TLE) surgery is associated with the best seizure outcome in adults, although its long-term results remain suboptimal. Retrospective pediatric studies suggest better figures whose determinants are poorly understood.OBJECTIVE:To conduct a systematic review and meta-analysis of studies on the efficacy of TLE surgery in children (age younger than 18 years) and adults.METHODS:We searched MEDLINE, Embase, and Cochrane Library for TLE surgery original research from January 1, 1990, until May 12, 2020. The outcome measures were seizure freedom since surgery and seizure freedom either at last or longest follow-up. We meta-analyzed the proportion of children and adults achieving either Engel I/International League Against Epilepsy (ILAE) 1 or Engel IA/ILAE 1A outcome by follow-up duration, type of surgery, histopathology, neuroimaging, quality of the studies, and publication period. We used a random effects model with Freeman-Tukey double arcsine transformation of proportions.RESULTS:From 40 409 records identified, we included 277 studies (30 848 patients). The proportions of patients achieving Engel I/ILAE 1 and Engel IA/ILAE 1A outcomes were 0.74 (95% CI, 0.69-0.78) and 0.61 (0.48-0.74) for children and 0.69 (0.67-0.71) and 0.56 (0.52-0.60) for adults. Histopathology significantly influenced Engel I/ILAE 1 outcome in adults but not in children (P < .0001), while the type of surgery significantly influenced Engel I/ILAE 1 outcome in children but not in adults.CONCLUSION:The proportion of seizure freedom after TLE surgery was higher in children, although not significantly. Histopathology and the surgical approach can influence seizure outcome, with age-related variability.

Validation of algorithms for selecting patients from healthcare administrative databases (HAD) is recommended. This PATHFINDER study section is aimed at testing algorithms to select rheumatoid arthritis (RA) patients from Tuscan HAD (THAD) and assessing RA diagnosis time interval between the medical chart date and that of THAD. A population was extracted from THAD. The information of the medical charts at the Rheumatology Unit of Pisa University Hospital represented the reference. We included first ever users of biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2014 and 2016 (index date) with at least a specialist visit at the Rheumatology Unit of the Pisa University Hospital recorded from 2013 to the index date. Out of these, we tested four index tests (algorithms): (1) RA according to hospital discharge records or emergency department admissions (ICD-9 code, 714*); (2) RA according to exemption code from co-payment (006); (3) RA according to hospital discharge records or emergency department admissions AND RA according to exemption code from co-payment; (4) RA according to hospital discharge records or emergency department admissions OR RA according to exemption code from co-payment. We estimated sensitivity, specificity, positive and negative predicted values (PPV and NPV) with 95% confidence interval (95% CI) and the RA diagnosis median time interval (interquartile range, IQR). Two sensitivity analyses were performed. Among 277 reference patients, 103 had RA. The fourth algorithm identified 96 true RA patients, PPV 0.78 (95% CI 0.70–0.85), sensitivity 0.93 (95% CI 0.86–0.97), specificity 0.84 (95% CI 0.78–0.90), and NPV 0.95 (95% CI 0.91–0.98). The sensitivity analyses confirmed performance. The time measured between the actual RA diagnosis date recorded in medical charts and that assumed in THAD was 2.2 years (IQR 0.5–8.4). In conclusion, this validation showed the fourth algorithm as the best. The time interval elapsed between the actual RA diagnosis date in medical charts and that extrapolated from THAD has to be considered in the design of future studies.

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Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.