Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis

IntroductionNatalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.Materials and methodsThis retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ‘Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment.ResultsOut of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups.DiscussionThe use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.

Conceptualizing Fixed-Interval Praise Delivery

This article provides a conceptual framework for using fixed-interval praise delivery in the educational setting. Fixed-interval praise delivery can be conceptualized as an antecedent-based strategy that disrupts the natural behavior to contingency relationship in a four-term contingency model (Establishing operation–Antecedent–Behavior–Consequence). Historically, teachers are trained to deliver praise as a consequence-based practice (i.e., contingently). This article describes how teachers can also use praise on a fixed interval as an antecedent-based practice. When praise is delivered on a fixed-interval schedule, educators directly manipulate the level of praise delivered to maintain or increase appropriate student behavior. Using praise as an antecedent-based strategy has the potential to establish and maintain high-quality student–teacher relationships, which positively impacts student behavior. Practical, applied examples and discussion of fixed-interval praise delivery are provided.

EFFECTS OF RESPONSE-REINFORCER RELATIONS ON THE MAINTENANCE OF COORDINATED RESPONDING UNDER SCHEDULES OF SIMULTANEOUS REINFORCEMENT

The effects of response-reinforcer relations on coordinated responding were investigated. Coordinated responding was defined as two lever presses, one by each rat that occurred within 500 ms of one another. Four conditions were arranged in an ABCB design. Coordinated responding was reinforced according to a fixed-ratio 6 (FR 6) schedule in Condition A. In Condition B, a response by each rat was required, independent of their temporal proximity, to produce water delivery under a variable-interval schedule. Condition C was a replication of Condition B, except that coordinated responding was required for reinforcer deliveries. All conditions involved simultaneous reinforcement, that is the rats received access to reinforcers at the same time. The results extended previous findings by demonstrating the requirement of coordinated responses to produce reinforcement affected both coordinated response rates and the proportion of such responses relative to the total responses in a session, in that both measures were higher in Conditions A and C than in Condition B. There also was control of the temporal distribution of coordinated responding by the type of schedule (FR or VI): A “break-and-run” pattern was observed under the FR schedule, and a constant response rate was observed under the VI schedule.

Ameliorating Episodic Memory Deficits in a Young Adult With Developmental (Congenital) Amnesia

Objectives: Although the spacing effect has been investigated extensively in a variety of populations, few studies have focused on individuals with hippocampal amnesia and none, to our knowledge, have investigated differences in performance as a function of spacing schedule in these cases. In the current study, we investigated the benefit of expanding and equal-interval, compared to massed, spacing schedules in a developmental amnesic person, H.C., who shows congenitally based abnormal development of the hippocampal memory system. Methods: Given the possibility of plasticity and reorganization in the developing brain, we investigated whether H.C. would benefit more from an expanding versus equal-interval schedule using a continuous recognition paradigm, even though this task has been shown to recruit structures within the medial temporal lobe, including the hippocampus. Results: H.C. and matched controls both showed a clear spacing effect, although neither group benefited more from an equal-interval or expanding spacing schedule. Conclusions: The results of the current study show that the spacing effect is an effective and clinically meaningful memory intervention technique that may be applied to clinical conditions known to affect hippocampal function and episodic memory early in life. (JINS, 2018, 24, 1003–1012)