Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Needle­based gastrocnemius lengthening: a novel ultrasound­guided noninvasive technique: part II-clinical results.

BACKGROUND: Isolated gastrocnemius contracture has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flatfoot, and metatarsalgia. Although many techniques are available for gastrocnemius recession, potential anesthetic, cosmetic, and wound-related complications can lead to patient dissatisfaction. Open and endoscopic recession techniques usually require epidural or general anesthesia, exsanguination of the lower extremities and stitches and can damage the sural nerve, which is not under the complete control of the surgeon at all stages of the procedure. The purpose of this study is to evaluate the clinical results of a surgical technique for gastrocnemius lengthening with a needle, as previously described in cadaver specimens. METHODS AND RESULTS: We performed a prospective study of ultrasound-guided gastrocnemius tendon lengthening in level II using a needle in 24 cases (19 patients) of gastrocnemius contracture. The study population comprised 12 males and 7 females. Mean age was 41 years (18-64). All but 5 recessions were bilateral and occurred simultaneously. The indication for the procedure was gastrocnemius contracture; although the patients also presented other conditions such as non-insertional Achilles tendinopathy in 6 patients (2 were bilateral), insertional Achilles calcifying enthesitis in 4 (1 was bilateral), metatarsalgia in 4, flexible flat foot in 1 and plantar fasciitis in 5 (2 were bilateral). The inclusion criteria were the failure of a previous conservative protocol, that the Silfverskiöld test was positive, and that the pathology suffered by the patient was within the indications for surgical lengthening of the patients and were described in the scientific literature. The exclusion criteria were that the inclusion criteria were not met, and patients with surgical risk ASA 3 or more and children. In these patients, although possible, it is preferable to perform the procedure in the operating room with monitoring, as well as in children since they could be agitated during the procedure at the office. We used the beveled tip of an Abbocath needle as a surgical scalpel. All patients underwent recession of the gastrocnemius tendon, as in an incomplete Strayer release. We evaluated pre- and postoperative dorsiflexion, outcomes, and procedural pain (based on a visual analog scale and the American Orthopedic Foot and Ankle Society scores), as well as potential complications. No damage was done to the sural bundle. RESULTS: Ankle dorsiflexion increased on average by 17.89°. The average postoperative visual analog score for pain before surgery was 5.78, 5.53 in the first week, 1.89 at 1 month, and 0.26 at 3 months, decreasing to 0.11 at 9 months. The mean postoperative American Orthopedic Foot and Ankle Society Ankle-Hindfoot score the average was 50.52 before surgery, 43.42 at 1 week, 72.37 at 1 month, 87.37 at 3 months, and 90.79 at 9 months. CONCLUSION: Ultrasound-guided needle lengthening of the gastrocnemius tendon is a novel, safe, and effective technique that enables the surgeon to check all the structures clearly, thus minimizing the risk of neurovascular damage. The results are encouraging, and the advantages of this approach include absence of a wound and no need for stitches. Recovery is fast and relatively painless. A specific advantage of ultrasound-guided needle lengthening of the gastrocnemius tendon is the fact that it can be performed in a specialist's office, with a very basic instrument set and local anesthesia, thus reducing expenses.

Phonological fluency norms for Spanish middle-aged and older adults provided by the SCAND initiative (P, M, & R).

OBJECTIVE: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. METHOD: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). RESULTS: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. CONCLUSIONS: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessment.

Trajectory tracking nonlinear H∞ controller for wheeled mobile robots with disturbances observer.

Wheeled Mobile Robots (WMRs) are systems with multiple industrial and civilian applications. Trajectory tracking is essential in many applications, such as surveillance, monitoring, and autonomous driving. However, in practical applications, a WMR is always affected by kinematic disturbances, state estimation error, and measurement noise, which may diminish the system's performance. Hence, this work proposes a novel observer-based H∞ controller that is robust against matched and unmatched disturbances. The proposed methodology compensates for disturbances through a disturbance observer, transforming the closed-loop system into a new one affected by uniformly bounded disturbances. Then, an H∞ controller is designed to make the WMR track a desired reference signal. A formal stability proof demonstrates the feasibility of the new proposal. Also, feedback and finite-time controllers are used to assess the novel controller. Numerical simulations and experimental results with a scaled autonomous car-like robot demonstrate the novel controller's efficiency and outstanding performance, despite disturbances when compared against finite-time and feedback controllers.

Surface characterization and interfacial activity of chitinase chi18-5 against chitosan in langmuir monolayers.

One of the challenges for producing active chitinase formulations relies on the gap between the laboratory tests and the biological scenarios where the enzyme will perform its function. In this work, we have employed different Langmuir monolayer arrays to evaluate the interfacial behavior of a recently purified recombinant chitinase, Chi18-5. We have demonstrated that two conformations exist for the chitinase at pH values close to its pI, showing very distinct structural properties at the air/aqueous interface. Enzyme activity was assessed by implementing different kinetic approaches and using a chitosan-1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) mixed film as organized substrate model membrane. Combining these strategies, we demonstrated that better catalytic efficiencies can be obtained for Chi18-5 at pH 5. Moreover, the chitinase activity at the air/aqueous interface can be tuned by introducing in situ pH modifications over the surrounding milieu. We also studied the changes in the topography at the mesoscale level using Brewster Angle Microscopy (BAM). We found that Chi18-5 segregated onto the chitosan domains of the membrane, showing differences in homogeneity depending on the pH imposed. Alternatively, pure Chi18-5 was tested for immobilization onto a hydrophilic activated solid support using the Langmuir-Blodgett technique. Atomic Force Microscopy (AFM) analyses showed successfully stabilization and preservation of molecular features attributed to the pH at which the enzyme deposition was performed.