Insights into the Window of Opportunity and Outcome Measures in Patients with Moderate to Severe Hidradenitis Suppurativa Treated with Secukinumab: A Real-World Study.

INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

Full-Length SMN Transcript in Extracellular Vesicles as Biomarker in Individuals with Spinal Muscular Atrophy Type 2 Treated with Nusinersen.

BACKGROUND: Three therapeutic strategies have radically changed the therapeutic scenario for spinal muscular atrophy (SMA). However, therapeutic response differs between individuals. There is a need to identify biomarkers to further assess therapeutic response and to better understand which variables determine the extent of response. METHODS: We conducted a study using an optimized digital droplet PCR-based method for the ultra-sensitive detection of SMN transcript in serum EVs from SMA 2 individuals treated with nusinersen over 14 months. In parallel, we investigated levels of serum and CSF neurofilament heavy chain (pNF-H) in the same cohort. RESULTS: Expression of flSMN transcript in EVs of SMA 2 individuals prior to nusinersen was lower than in controls (0.40 vs 2.79 copies/ul; p < 0.05) and increased after 14 months of nusinersen (0.40 vs 1.11 copies/ul; p < 0.05). The increase in flSMN with nusinersen was significantly higher in younger individuals (p < 0.05). Serum pNF-h was higher in non-treated individuals with SMA 2 than in controls (230.72 vs 22.88 pg/ml; p < 0.05) and decreased with nusinersen (45.72 pg/ml at 6 months, 39.02 pg/ml at 14 months). CSF pNF-h in SMA 2 individuals also decreased with nusinersen (248.04 pg/ml prior to treatment, 197.10 pg/dl at 2 months, 104.43 pg/dl at 6 months, 131.03 pg/dl at 14 months). CONCLUSIONS: We identified an increase of flSMN transcript in serum EVs of SMA 2 individuals treated with nusinersen that was more pronounced in the younger individuals. Our results indicate that flSMN transcript expression in serum EVs is a possible biomarker in SMA to predict or monitor the response to treatment.

Cognitive functioning as predictor and marker of response to repetitive transcranial magnetic stimulation in depressive disorders: A systematic review.

OBJECTIVE: Cognitive performance in Major Depressive Disorder (MDD) is frequently impaired and related to functional outcomes. Repetitive Transcranial Magnetic Stimulation (rTMS) may exert its effects on MDD acting both on depressive symptoms and neurocognition. Furthermore, cognitive status could predict the therapeutic response of depressive symptoms to rTMS. However, cognitive performances as a predictor of rTMS response in MDD has not been thoroughly investigated. This review aims to evaluate the role of pre-treatment cognitive performance as a predictor of clinical response to rTMS, and the effects of rTMS on neurocognition in MDD. METHOD: A systematic review of studies evaluating neurocognition in MDD as an outcome and/or predictor of response to rTMS was conducted using PubMed/Medline and Embase. RESULTS: Fifty-eight articles were identified: 25 studies included neurocognition as a predictor of response to rTMS; 56 used cognitive evaluation as an outcome of rTMS. Baseline cognitive performance and cognitive improvements after rTMS predicted clinical response to rTMS. Moreover, rTMS improved cognition in MDD. CONCLUSIONS: Cognitive assessment could predict improvement of depression in MDD patients undergoing rTMS and help selecting patients that could have beneficial effects from rTMS. A routine cognitive assessment might stratify MDD patients and track rTMS related cognitive improvement.

Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients.

BACKGROUND AND PURPOSE: The antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator-free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients. METHODS: Thirty-four SMA patients were included. We applied next generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE) was conducted at baseline and 6 months after initiation of nusinersen therapy to assess motor function. Patients changing by ≥3 or ≤0 points in the HFMSE total score were considered to be responders or nonresponders, respectively. RESULTS: Lower baseline levels of two muscle microRNAs (miR-206 and miR-133a-3p), alone or in combination, predicted the clinical response to nusinersen after 6 months of therapy. Moreover, miR-206 levels were inversely correlated with the HFMSE score. CONCLUSIONS: Lower miR-206 and miR-133a-3p in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinersen in later onset SMA patients and call for testing the ability of miRNAs to predict more sustained long-term benefit.

A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern.

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors.

Vaccination against SARS-CoV-2 is currently the best tool in the fight against the COVID-19 pandemic. However, there are limited data on its efficacy and safety after hematopoietic stem cell transplantation (HCT). We present the results of a prospective analysis of the humoral response to two doses of BNT162b2 mRNA vaccine in 93 adult patients, including 29 after autologous HCT (autoHCT) and 64 after allogeneic HCT (alloHCT). Positive anti-SARS-CoV-2 antibodies were detected before vaccination in 25% of patients despite a negative medical history of COVID-19. Seroconversion after vaccination was achieved in 89% of patients after alloHCT and in 96% after autoHCT, without grade 3/4 adverse events. Post-vaccination anti-SARS-CoV-2 antibody level correlated with the time from transplant and absolute B-cell count at the vaccination. In univariate analysis restricted to the alloHCT group, short time since transplantation, low B-cell count, low intensity conditioning, GvHD, and immunosuppressive treatment at the vaccination were associated with lack of seroconversion. In the multivariate model, the only negative predictor of seroconversion remained treatment with calcineurin inhibitor (CNI). In conclusion, the BNT162b2 mRNA vaccine is highly immunogenic in patients after HCT, but treatment with CNI at the time of vaccination has a strong negative impact on the humoral response.

MIN score predicts primary response to infliximab/adalimumab and vedolizumab therapy in patients with inflammatory bowel diseases.

Infliximab/adalimumab (IFX/ADA) and vedolizumab (VDZ) are the most widely used biologics in inflammatory bowel diseases. Current models used to predict their efficacies are restricted to either Crohn's disease or ulcerative colitis or to only one type of biologic, which makes them limited in external validation. We therefore designed a comprehensive comparison among these models to identify the most meaningful predictors for patient responses. Several biomarkers and models were compared for their abilities to predict both IFX/ADA and VDZ responses by receiver operating characteristic curves. Least absolute shrinkage and selection operator regression was adopted to determine a simplified gene signature. Verification was performed in biopsy samples by immunohistochemical staining. The GIMATS module (based on counts of IgG plasma cells, inflammatory monocytes, activated T cells, and stromal cells) had the best overall performance for response prediction in both biologics (IFX/ADA, AUC = 0.720-0.853; VDZ, AUC = 0.661-0.728). Based on this module, patients were equally divided into 3 groups: M type (GIMATS-low, metabolism), with a preference for IFX/ADA; I type (GIMATS-high, immune), with a preference for VDZ; and N type (GIMATS-medium, normal), with no preference for either treatment. Furthermore, to improve clinical utility, a simplified 6-gene model, MIN score, was established to determine the baseline expression of G0S2, S100A9, SELE, CHI3L1, MMP1 and CXCL13 and function as a substitute for GIMATS module. Our study suggested that the classification of metabolic or immune type by MIN score was valuable for IBD diagnosis to assist with selection of IFX/ADA and VDZ.

Abatacept in rheumatoid arthritis: survival on drug, clinical outcomes, and their predictors-data from a large national quality register.

BACKGROUND: There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. METHODS: RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of ≥ 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. RESULTS: There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p < 0.001), with longer survival in bionaïve patients. Men (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.74-0.98) and methotrexate users (HR 0.85, 95% CI 0.76-0.95) were less likely to discontinue abatacept, whereas a high pain score predicted discontinuation (HR 1.14 per standard deviation, 95% CI 1.07-1.20). The absence of previous bDMARD exposure, male sex, and a low HAQ score were independently associated with LUNDEX-corrected EULAR good response. The absence of previous bDMARD exposure also predicted LUNDEX-corrected HAQ response. CONCLUSIONS: In this population-based study of RA, bDMARD naïve patients and male patients were more likely to remain on abatacept with a major clinical response.

Response Predictors in Chronic Migraine: Medication Overuse and Depressive Symptoms Negatively Impact Onabotulinumtoxin-A Treatment.

Background: Despite numerous studies that have investigated clinical, radiological, and biochemical response predictors, the clinical profile of those patients who might benefit from OnabotulinumtoxinA is still missing. The aim of the present study was to identify potential OnabotulinumtoxinA response predictors among several clinical characteristics and confirm OnabotulinumtoxinA efficacy and safety in chronic migraine (CM) prevention. Methods: The study was conducted at the Headache Center-Neurology Clinic-Spedali Civili Hospital of Brescia. Eighty-four consecutive CM patients were enrolled, with a mean age of 48 years (SD 9.7) and a mean disease duration of 10.1 years (SD 6.6). The mean reported headache-days frequency was 22.5 (SD 5.9) per month, while the mean number of severe headache-days was 15.2 (SD 8.9) with a mean monthly medication intake of 33.2 (SD 5.6). The clinical characteristics analyzed as potential response predictors were: gender, disease duration, migraine characteristics (location, side constancy, unilateral autonomic and neurovegetative symptoms), previous prophylactic treatments, add-on therapies, withdrawal therapies, psychiatric (anxiety and depression symptoms) comorbidities and medication overuse. Results: A significant reduction from baseline to 3, 6, 9, and 12 month treatment cycles in total headache days, high intensity headache days and triptans consumption per month was found. Depressive symptoms and medication overuse negatively predicted OnabotulinumtoxinA outcome. Conclusions: Our results confirm the efficacy and safety of OnabotulinumtoxinA in CM. Depressive comorbidity and medication overuse, among all clinical variables, were the only significant response predictors. Such findings provide interesting insights regarding patients selection for OnabotulinumtoxinA treatment as, with the introduction of anti calcitonin gene-related (CGRP) monoclonal antibodies, clinicians will have to thoroughly judge and tailor among the many available therapeutic options now available. Future research might be needed to confirm our findings, in particular for its therapeutic implications.

Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: data from the GLADAR cohort.

OBJECTIVES: To identify baseline predictors of remission and low disease activity (LDA) in early rheumatoid arthritis (RA) from the GLADAR (Grupo Latino Americano De estudio de la Artritis Reumatoide) cohort. METHODS: Patients with 1- and 2-year follow-up visits were included. Remission and LDA were defined by DAS28-ESR (< 2.6 and ≤ 3.2, respectively). Baseline predictors examined were gender, ethnicity, age at diagnosis, socioeconomic status, symptoms' duration, DMARDs, RF, thrombocytosis, anemia, morning stiffness, DAS28-ESR (and its components), HAQ-DI, DMARDs and corticosteroid use, and Sharp-VDH score. Multivariable binary logistic regression models (excluding DAS28-ESR components to avoid over adjustment) were derived using a backward selection method (α-level set at 0.05). RESULTS: Four hundred ninety-eight patients were included. Remission and LDA/remission were met by 19.3% and 32.5% at the 1-year visit, respectively. For the 280 patients followed for 2 years, these outcomes were met by 24.3% and 38.9%, respectively. Predictors of remission at 1 year were a lower DAS28-ESR (OR 1.17; CI 1.07-1.27; p = 0.001) and HAQ-DI (OR 1.48; CI 1.04-2.10; p = 0.028). At 2 years, only DAS28-ESR (OR 1.40; CI 1.17-1.6; p < 0.001) was a predictor. Predictors of LDA/remission at 1 year were DAS28-ESR (OR 1.42; CI 1.26-1.61; p < 0.001), non-use of corticosteroid (OR 1.74; CI 1.11-2.44; p = 0.008), and male gender (OR 1.77; CI 1.2-2.63; p = 0.036). A lower baseline DAS28-ESR (OR 1.45; CI 1.23-1.70; p < 0.001) was the only predictor of LDA/remission at 2 years. CONCLUSIONS: A lower disease activity consistently predicted remission and LDA/remission at 1 and 2 years of follow-up in early RA patients from the GLADAR cohort. Key Points • In patients with early RA, a lower disease activity at first visit is a strong clinical predictor of achieving remission and LDA subsequently. • Other clinical predictors of remission and LDA to keep in mind in these patients are male gender, non-use of corticosteroids and low disability at baseline. • Not using corticosteroids at first visit is associated with a lower disease activity and predicts LDA/remission at 1 year in these patients.

A time-to-event analysis describing virologic response in patients with chronic hepatitis C infection.

The objective of this project was to describe longitudinal change in chronic hepatitis C virologic reponse using time-to-event (TTE) analysis and to identify patient characteristics that determine the dynamics of this change. We compiled demographic, clinical, and genetic data from 715 chronic hepatitis C virus (HCV) patients treated with pegylated interferon (PEG-IFN) alfa-2a and ribavirin. TTE modelling described the time between antiviral treatment initiation and the first observation of undetectable HCV RNA. A lognormal TTE model was selected to describe time to first undetectable HCV RNA. The identified predictors of prolonged time to achieve undetectable HCV RNA include HCV genotype 1, low pre-treatment ALT level, older age, or with elevated baseline haemoglobin level. In conclusion, a cohort of patients with low probability of achieving SVR can be identified. This project identifies patients with a low risk of responding to PEG-IFN alfa-2a and ribavirin combination.

Predicting antidepressant response using early changes in cognition: A systematic review.

BACKGROUND: Despite the widespread use of antidepressants in clinical practice, the current trial-and-error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response. Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms, the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD. METHODS: A systematic review of studies evaluating early cognitive change as a predictor of later treatment response in MDD was conducted using PubMed/Medline, Embase and PsychINFO. RESULTS: A total of seven articles were identified. The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD. This was shown across antidepressant classes (i.e., SSRIs, SNRIs, NRIs, melatonergic antidepressants) and forms of therapy (i.e., pharmacotherapy, rTMS). The results depict an emerging trend towards early changes in facial emotion recognition (i.e., a hot cognitive process) as a predictor of treatment outcome. LIMITATIONS: Our qualitative analysis reflects a very limited number of studies. Moreover, there was significant heterogeneity in the evaluation of cognition across studies. Future research should aim to parse out this heterogeneity by evaluating the relative predictive value of different measures of cognition. CONCLUSION: The identification of reliable early treatment predictors of antidepressant response would be clinically significant, enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues.

[Response predictors for physical training HFrEF patients].

PURPOSE: To identify different types and possible predictors of physical rehabilitation (PR) response in reduced ejection fraction heart failure (HFrEF) patients, selected on the basis of achievement the lactate threshold during cardiopulmonary exercising test (CPET). METHODS: 64 patients, chronic heart failure (CHF) NYHA II-III functional class were included in our study. Mean age 54±12,5 years, body mass index (BMI) 26,5±6,4 kg/m2, ejection fraction (EF) 26,4±1,4 %, NYHA II: III (67 %: 33 % patients). The original estimated results of physical examination, laboratory parameters, CPET, quality of life (QOL), exercise tolerance (ET) and echocardiography (EchoCG). Physical rehabilitation (PR) efficiency was estimated on the basis of peak oxygen uptake (VO2peak), QOL and ET dynamics after 1,3 and 6 months; EF dynamics was estimated after 6 months. Data were statistically processed using software package "Statistika, 9.0". RESULTS: After 6 months PR EF increased by 7,5±0,5 %, QOL - 17.5±8 points, ET - 9.5±1 points and VO2 peak - 4.4 ml/min/kg, end-diastolic volume decreased by 6±2.0 ml from baseline (p1,2,3,4, respectively). Echocardiography, CPET, QOL and ET improvement revealed a significant number of patients (EF - 48 %, VO2 peak - 64 %, QOL - 64 %, ET - 67 % of patients, respectively). Revealed a strong positive correlation between the initial values of VO2 peak and EF (rEF=0,4, p), and between baseline levels of sodium, haemoglobin and the of PR efficiency (rNa= 0,41, p,0,05; rHb = 0,45, p.

Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols.

Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of 'omics' technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment.

Bronchial thermoplasty: activations predict response.

BACKGROUND: Bronchial thermoplasty (BT) is an emerging bronchoscopic intervention for the treatment of severe asthma. The predictive factors for clinical response to BT are unknown. We examined the relationship between the number of radiofrequency activations applied and the treatment response observed. METHODS: Data were collected from 24 consecutive cases treated at three Australian centres from June 2014 to March 2016. The baseline characteristics were collated along with the activations delivered. The primary response measure was change in the Asthma Control Questionnaire-5 (ACQ-5) score measured at 6 months post BT. The relationship between change in outcome parameters and the number of activations delivered was explored. RESULTS: All patients met the ERS/ATS definition for severe asthma. At 6 months post treatment, mean ACQ-5 improved from 3.3 ± 1.1 to 1.5 ± 1.1, p < 0.001. The minimal clinically significant improvement in ACQ-5 of ≥0.5 was observed in 21 out of 24 patients. The only significant variable that differed between the 21 responders and the three non-responders was the number of activations delivered, with 139 ± 11 activations in the non-responders, compared to 221 ± 45 activations in the responders (p < 0.01). A significant inverse correlation was found between change in ACQ-5 score and the number of activations, r = -0.43 (p < 0.05). CONCLUSIONS: The number of activations delivered during BT has a role in determining clinical response to treatment.

Clinical value of on-treatment HCV RNA levels during different sofosbuvir-based antiviral regimens.

BACKGROUND & AIMS: The European Association for the Study of the Liver (EASL) guidelines recommend HCV RNA measurements at specific time points during sofosbuvir(SOF)-therapy. However, it remains unclear, how these results should be interpreted. We aimed to analyze whether on-treatment HCV RNA levels predict relapse comparing the CobasAmpliPrep/CobasTaqMan v2.0 (CAP/CTM) and Abbott RealTime HCV (ART) assays. METHODS: Samples were collected from 298 patients (HCV genotypes; GT1-5) at weeks (w) 0, 1, 2, 4, 8, 12, 16, 20 and 24 during SOF-based therapy at two university clinics and tested for HCV RNA level by CAP/CTM and ART. Patients were treated with SOF/ribavirin (RBV) 12/24 w (n=99), pegylated-interferon-alfa (PegIFN)/SOF/RBV 12 w (n=51), SOF/simeprevir (SMV)±RBV 12 w (n=69) or SOF/daclatasvir±RBV 12/24 w (n=79). RESULTS: HCV RNA levels during the first 4weeks of SOF/RBV therapy were significantly lower in GT3 patients who achieved SVR compared with those who relapsed. All GT3 patients with a week 2 result <45IU/ml by CAP/CTM achieved SVR but only 33% of those with ⩾45IU/ml (p=0.0003). Similar results were documented with ART and 60IU/ml as cut-off (SVR: 100% vs. 29%; p=0.0002). In contrast, HCV RNA levels during early treatment phases were not significantly related to relapse in patients treated with other SOF-based regimens. Residual HCV RNA was frequently detected by ART at later stages of therapy. However, SVR rates remained high in these patients. At the end of SOF/SMV±RBV therapy HCV RNA was detectable with ART in 20% of patients, of whom 92% achieved SVR. CONCLUSIONS: HCV RNA levels assessed at week 2 of SOF/RBV therapy can predict relapse in GT3-patients. Detectable HCV RNA results at later stages during SOF-based therapy may occur frequently with the more sensitive ART. However, this should not lead to treatment extension. LAY SUMMARY: We analyzed the predictive value of hepatitis C virus (HCV) RNA levels measured at different time points for treatment efficacy. We found that the level of HCV RNA measured at week 2 of antiviral therapy can be used to predict treatment success in patients with HCV genotype 3 infection treated with sofosbuvir and ribavirin but not in patients treated with other sofosbuvir-based regimens. Low level HCV RNA is frequently detected by the RealTime HCV assay during later stages of antiviral therapy. However, this is not associated with reoccurrence of HCV RNA after the end of treatment.

Predictors of response to etanercept in polyarticular-course juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study was to determine demographic, clinical, articular and laboratory variables predicting etanercept response in JIA. METHODS: A total of 863 patients registered in the BIKER registry were included. Predictors of response for ACR paediatric criteria (PedACR) 30, 70 and 90 were analysed by bivariate analysis and logistic regression. RESULTS: After 6 months, 81.9% of the included patients fulfilled the PedACR30, 55.2% the PedACR70 and 31.3% the PedACR90 criteria. In bivariate analyses, factors positively correlated with a PedACR70/90 response were extended oligoarthritis JIA category, lower age at the start of treatment, shorter disease duration until treatment start, no concomitant use of corticosteroids, duration of morning stiffness, parents' global assessment of overall well-being, lower Childhood Health Assessment Questionnaire (CHAQ) and higher ESR and ANA. Correlation between the JIA category systemic arthritis and response was significantly negative. Predictive factors for PedACR70 in multivariate logistic regression analysis were CHAQ [odds ratio (OR) = 0.70], ESR (OR = 1.02) and concomitant treatment with corticosteroids (OR = 0.68). Age at treatment start (OR = 0.94) and the systemic arthritis JIA category (OR = 0.28) were predictive for a PedACR70. We found no sufficiently distinctive models for PedACR30 or 90. CONCLUSION: Parameters predicting a high-grade response to a 6-month course of etanercept were identifiable and included age at treatment start, disease duration before treatment, JIA category other than systemic arthritis, CHAQ, parents' global assessment and concomitant corticosteroids.

Effects of methylphenidate on acute math performance in children with attention-deficit hyperactivity disorder.

OBJECTIVE: Examine the short-term (acute) effects of methylphenidate (MPH) on math performance in children with attention-deficit hyperactivity disorder (ADHD) and what factors predict improvement in math performance. METHOD: One hundred ninety-eight children with ADHD participated in a double-blind, placebo-controlled, randomized crossover MPH trial. Math response to MPH was determined through administration of math problems adjusted to their academic level during the Restricted Academic Situation Scale (RASS). Student t tests were conducted to assess change in math performance with psychostimulants. Correlation between change on the RASS and change on the math performance was also examined. Linear regression was performed to determine predictor variables. RESULTS: Children with ADHD improved significantly in their math with MPH (P < 0.001). The degree of improvement on the RASS (which evaluates motor activity and orientation to task) and on math performance on MPH was highly correlated. A child's age at baseline and Wechsler Individual Achievement Test (WIAT)-Numerical Operations standard scores at baseline accounted for 15% of variances for acute math improvement. CONCLUSIONS: MPH improves acute math performance in children with ADHD. Younger children with lower math scores (as assessed by the WIAT) improved most on math scores when given psychostimulants. CLINICAL TRIAL REGISTRATION NUMBER: NCT00483106.

Objectif : Examiner les effets à court terme (aigus) du méthylphénidate (MPH) sur la performance en mathématique chez des enfants souffrant du trouble de déficit de l'attention avec hyperactivité (TDAH), et quels facteurs prédisent une amélioration de la performance en math. Méthode : Cent quatre-vingt-dix-huit enfants souffrant du TDAH ont participé à un essai de MPH croisé, randomisé, à double insu et contrôlé avec placebo. La réponse du MPH en math a été déterminée par l'administration de problèmes de math ajustés à leur niveau scolaire durant la Restricted Academic Situation Scale (RASS). Les tests t de Student ont été menés afin d'évaluer le changement de la performance en math avec les psychostimulants. La corrélation entre le changement à la RASS et le changement de la performance en math a aussi été examinée. Une régression linéaire a été exécutée pour déterminer les variables prédictives. Résultats : Les enfants souffrant du TDAH se sont améliorés significativement en math avec le MPH (P < 0,001). Le degré d'amélioration à la RASS (qui évalue l'activité motrice et l'orientation dans les tâches) et dans la performance en math avec MPH était hautement corrélé. L'âge de l'enfant au départ et les scores normaux au départ au Wechsler Individual Achievement Test (WIAT) ­ des opérations numériques représentaient 15 % des variances d'amélioration aiguë en math. Conclusions : Le MPH améliore la performance aiguë en mathématique chez les enfants souffrant du TDAH. Les enfants plus jeunes qui ont de moins bons scores en math (évalué par le WIAT) ont surtout amélioré leurs scores en math lorsqu'ils ont reçu des psychostimulants. Numéro d'enregistrement d'essai clinique : NCT00483106.

Prediction of sustained virologic responses to combination therapy of pegylated interferon-α and ribavirin in patients with chronic hepatitis C infection.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-α combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) infection. PATIENTS AND METHODS: Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. RESULTS: Of the 48 treated patients, 25 (52%) were females and 27 (56%) were Saudi. The mean age was 43 years (43 ± 10 years). Twenty-four (50%) had genotype-4, and 26 (54%) had liver biopsy. The overall SVR rate was 75% (36/48) and was 83.3% (20/24) among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR), defined as a drop of ≥2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001). However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003) and low baseline viral load (P = 0.048) were highly predictive of SVR. CONCLUSIONS: Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.