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Objective: This study aimed to evaluate safety (infusion‐related reactions [IRRs]) and patient satisfaction (patient‐reported outcomes [PROs]) for at‐home ocrelizumab administration for patients with multiple sclerosis (MS). Methods: This open‐label study included adult patients with an MS diagnosis who had completed a ≥ 600‐mg ocrelizumab dose, had a patient‐determined disease steps score of 0 to 6 and had completed PROs. Eligible patients received a 600‐mg ocrelizumab home‐based infusion over 2 h, followed by 24‐h and 2‐week post‐infusion follow‐up calls. IRRs and adverse events (AEs) were documented during infusions and follow‐up calls. PROs were completed before and 2 weeks post infusion. Results: Overall, 99 of 100 expected patients were included (mean [SD] age, 42.3 [7.7] years; 72.7% female; 91.9% White). The mean (SD) infusion time was 2.5 (0.6) hours, and 75.8% of patients completed their ocrelizumab infusion between 2 to 2.5 h. The IRR incidence rate was 25.3% (95% CI: 16.7%, 33.8%)—similar to other shorter ocrelizumab infusion studies—and all AEs were mild/moderate. In total, 66.7% of patients experienced AEs, including itch, fatigue, and grogginess. Patients reported significantly increased satisfaction with the at‐home infusion process and confidence in the care provided. Patients also reported a significant preference for at‐home infusion compared with prior infusion center experiences. Interpretation: IRRs and AEs occurred at acceptable rates during in‐home infusions of ocrelizumab over a shorter infusion time. Patients reported increased confidence and comfort with the home infusion process. Findings from this study provide evidence of the safety and feasibility of home‐based ocrelizumab infusion over a shorter infusion period. [ABSTRACT FROM AUTHOR]

Introduction: Studies investigating rates and risk factors for serious safety events (SSEs) during rituximab treatment of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and related disorders are limited. Methods: Rituximab‐treated patients with MS, NMOSD, or related disorders at the Rocky Mountain and New York University MS Care Centers were included. The follow‐up period was defined as the time from the initial dose of rituximab up to 12 months of last dose of rituximab or ocrelizumab (in patients who switched). Clinician‐reported and laboratory data were retrospectively collected from electronic medical records. Results: One‐thousand patients were included comprising 907 MS, 77 NMOSD, and 16 related disorders. Patients had a mean follow‐up of 31.1 months and a mean cumulative rituximab dose of 4012 mg. Of the 169 patients who switched to ocrelizumab, the mean ocrelizumab dose was 1141 mg. Crude incidence rate per 1000 person‐years (PY) for lymphopenia was 19.2, neutropenia 5.6, and hypogammaglobulinemia 17.8. Infections resulting in either hospitalization, IV antibiotics, or using antibiotics ≥14 days occurred at a rate of 38.6/1000 PY. Risk factors for infection were duration of therapy, male gender, increased disability, prior exposure to immunosuppression/chemotherapy, lymphopenia, and hypogammaglobulinemia. Particularly, wheelchair‐bound patients had 8.56‐fold increased odds of infections. Crude incidence rates of malignant cancer were 3.5, new autoimmune disease 2.3, thromboembolic event 3.1, and mortality of 5.4 per 1000 PY. Interpretation: Rates of SSEs in patients with MS, NMOSD, and related disorders were low. Through properly assessing risk:benefit of B‐cell depleting therapy in neuroinflammatory disorders and continual monitoring, clinicians may decrease the risk of serious infections. [ABSTRACT FROM AUTHOR]

Introduction: Limited comparative effectiveness data for rituximab (RTX) versus natalizumab (NTZ), fingolimod (FTY), and dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS) exist. Methods: Clinician‐reported data on patients prescribed RTX, NTZ, FTY, or DMF for the treatment of MS at the Rocky Mountain MS Center at the University of Colorado were retrospectively collected. Outcomes included a composite effectiveness measure consisting of clinical relapse, contrast‐enhancing lesions, and/or new T2 lesions, individual effectiveness outcomes, and discontinuation. Logistic regression was used on patients matched by propensity scores and using average treatment effect on treated doubly robust weighting estimator. Results: A total of 182, 451, 271, and 342 patients initiated RTX, NTZ, FTY, and DMF and were followed for 2 years. Before and after adjustment, the odds of experiencing disease activity was significantly higher for FTY [adjusted OR (aOR) = 3.17 (95% CI: 1.81–5.55), P < 0.001].and DMF [aOR = 2.68 (95% CI:1.67–4.29), P < 0.001], and similar for NTZ [aOR = 1.36 (95% CI:0.83–2.23), P = 0.216] versus RTX. When examining months 6–24, NTZ demonstrated higher odds of disease activity compared to RTX [aOR = 2.21 (95% CI: 1.20–4.06), P = 0.007]. Similar odds of discontinuation were seen between NTZ and RTX [aOR = 1.39 (95% CI: 0.88–2.20), P = 0.157]; however, FTY [aOR = 2.02 (95% CI: 1.24–3.30), P = 0.005] and DMF [aOR = 3.27 (95% CI: 2.15–4.97), P < 0.001] had greater odds of discontinuation than RTX. Interpretation: RTX demonstrated superior effectiveness and discontinuation outcomes compared to FTY and DMF. Although RTX demonstrated similar effectiveness and discontinuation compared to NTZ, RTX had superior effectiveness during months 6–24 and fewer discontinuations when excluding discontinuations due to insurance issues. Results suggest superiority of RTX in reducing disease activity and maintaining long‐term treatment in a real‐world MS cohort. [ABSTRACT FROM AUTHOR]

Objective: To compare 2‐year effectiveness and discontinuation of natalizumab (NTZ) versus fingolimod (FTY) and dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). Methods: Patients prescribed NTZ, FTY, or DMF at the Rocky Mountain MS Center at University of Colorado were identified. Clinician‐reported data were retrospectively collected. Outcomes include a composite effectiveness measure consisting of new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse, individual effectiveness outcomes and discontinuation over 2 years. Logistic regression was used for data analysis on patients matched by propensity scores and using ATT doubly robust weighting estimator. Results: A total of 451, 271, and 342 patients were evaluated on NTZ, FTY, and DMF over 2 years, respectively. Patients had a mean age of 39.8 (NTZ), 42.5(FTY), and 45.8 (DMF) years; were predominantly female (76.7% NTZ; 72.0% FTY; 69.6% DMF); and had a mean MS disease duration of 11–12 years for all groups. At ≤24 months, 22.2%, 34.7%, and 33.6% experienced a new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse on NTZ, FTY, and DMF, respectively. Using ATT doubly robust weighting estimator, FTY versus NTZ and DMF versus NTZ had an odds ratio of 2.00 (95%CI:[1.41–2.85], P < 0.001) and 2.38 [95% CI: 1.68–3.37], P < 0.001) respectively, for experiencing a new T2 lesion, gadolinium enhancing lesion, and/or clinical relapse. At ≤24 months, 32.6%, 34.3%, and 47.1% discontinued NTZ, FTY, and DMF, respectively. The majority of discontinuations were due to becoming JCV positive(12.6%) for NTZ and due to adverse events for both FTY(17%) and DMF(24.0%). Interpretation: NTZ appears to be more effective and tolerable than FTY and DMF. [ABSTRACT FROM AUTHOR]

Background and Purpose: Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD).Methods: MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months. Patients with active disease at baseline (245, 41.5%) were defined as those who had one or more relapses in the year previous starting fingolimod, and/or displayed gadolinium enhancing lesions(s) at baseline MRI scan, whereas patients with NEAD at baseline (345, 58.5%) did not fulfill these criteria. Annualized percentage brain volume change (PBVC) and percentage lateral ventricle volume change (PLVVC) over the follow-up were analyzed in both groups.Results: Over the follow-up, the rate of PBVC was -.38% in active disease and -.25% in NEAD patients (P = .076), whereas PLLVC was 1.76% in active disease and .28% in NEAD patients (P = .046). No changes in timed 25-foot walk (P = .619) and Expanded Disability Status Scale (P = .275) scores or MRI lesion accumulation (P > 0.08) were detected, although the active disease group had a higher proportion of relapses during the follow-up period (P = .02).Conclusions: The study provides real-world evidence that rate of brain atrophy in MS patients with underlying active disease and NEAD in fingolimod treated patients is below the established pathological cutoff for loss of whole brain volume (>-.4%) or expansion of lateral ventricles (> 3.5%). [ABSTRACT FROM AUTHOR]

The leader protease (L pro ) from foot-and-mouth disease virus (FMDV) has the ability to cleave eIF4G, leading to a blockade of cellular protein synthesis. In contrast to previous reports, our present findings demonstrate that FMDV L pro is able to increase translation driven by FMDV IRES. Additionally, inactivation of eIF2 subsequent to phosphorylation induced by arsenite or thapsigargin in BHK cells blocks protein synthesis directed by FMDV IRES, whereas in the presence of L pro , significant translation is found under these conditions. This phenomenon was also observed in cell-free systems after induction of eIF2 phosphorylation by addition of poly(I:C). [ABSTRACT FROM AUTHOR]

Objectives. The study aims at evaluating the suitability of applying the transtheoretical model (TTM) stage-of-change construct to the treatment with dialectical behaviour therapy (DBT) of borderline personality disorder (BPD). Design. Stages of change were assessed by means of the University of Rhode Island Change Assessment (URICA) scale prior to and after 3 months DBT skills group psychotherapy. Method. The sample was comprised of 79 people with BPD (86% of females) at pretreatment, and 42 patients (80% of females) at post-treatment. All patients were referred from clinical services and diagnosed by means of two semi-structured interviews. Results. In pre-treatment assessment, precontemplation scores correlated signified- cantly and negatively with the other subscales (contemplation, action, and maintenance) and these three subscales also correlated significantly and positively with each other. The precontemplation stage was directly related to drop-out from the DBT group. The action subscale and the committed action (CA) composite scorewere significantly higher by the end of the DBT group treatment. However, with the absence of a control group it cannot be assured that these increases were directly related to DBT intervention. Conclusions. In this observational design the stages of change of TTM seemed applicable to the DBT conceptualization of BPD and could further our understanding of the process of change in people with BPD treated with DBT. [ABSTRACT FROM AUTHOR]

Ground water injection and sampling systems were developed for bacterial transport experiments in both homogenous and heterogeneous unconsolidated, surficial aquifers. Two types of injection systems, a large single tank and a dynamic mixing tank, were designed to deliver more than 800 L of amended ground water to the aquifer over 12 hours, without altering the ground water temperature, pH, Eh, or dissolved gas composition. Two types of multilevel samplers (MLSs) were designed and installed. Permanent MLSs performed well for the homogenous surficial aquifer, but their installation procedure promoted vertical mixing, which could obfuscate experimental data obtained from vertically stratified, heterogeneous aquifers. A novel, removable MLS was designed to fit in 2- and 4-inch wells. Expandable O-rings between each sampling port hydraulically isolated each port for sample collection when a nut was tightened at the land surface. A low-cost vacuum manifold system designed to work with both MLS designs used 50 mL centrifuge tubes to efficiently sample 12 MLS ports with one peristaltic pump head. The integrated system was developed and used during four field campaigns over a period of three years. During each campaign, more than 3000 ground water samples were collected in less than one week. This system should prove particularly useful for ground water tracer, injection, and push-pull experiments that require high-frequency and/or high-density sampling. [ABSTRACT FROM AUTHOR]

Cellular parameters of the seminogram have been previously shown to correlate with L-carnitine concentration in the seminal fluid. Carnitine is involved in a variety of metabolic processes playing an important role in maintaining an active oxidative phosphorylation (OXPHOS). Recently, we have found a significant association between the specific activities of the respiratory chain complexes and the seminogram parameters and here we have studied the relationship between the spermatozoa OXPHOS activities and L-carnitine concentration in the seminal plasma. Carnitine, but not prostatic secretions, positive and significantly correlate with mitochondrial respiratory complex activities and the citric acid cycle enzymes citrate synthase and succinate dehydrogenase. It is remarkable that the ratios of the respiratory chain complexes to citrate synthase or succinate dehydrogenase, significant but negatively correlated with L-carnitine concentration. As carnitine in seminal plasma is secreted from the epididymis our results strongly suggest that relationships between carnitine secretion, seminal quality and OXPHOS activities could be because of a parallel response to the same regulatory event. [ABSTRACT FROM AUTHOR]