Although the cognitive flexibility (CF) of preschool children has been extensively studied, the development of CF in children around three years old is unclear. This study aimed to investigate the CF of three-year-olds in a stepwise rule-induction task (sRIT) comprising nine steps in which children are encouraged to switch attention to a new rule and then implicitly inhibit the old one. A pair of boxes was displayed at each step, and children aged 2.5 to 3.5 years were asked to select the target. When children learned a rule (e.g., the shape rule), they were encouraged to switch rules through negative feedback. The results showed that most children (81.10%) passed at least one of the two sets of the sRIT, and children over the age of three years performed better than those under three years. Additionally, a positive correlation existed between rule switching and rule generalization, whereby the old rule was implicitly inhibited. These findings indicate that age three might be a milestone in the development of CF, and inhibitory control might play a vital role in rule switching.

BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline.
METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria.
RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review.
CONCLUSIONS: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. We describe a class of aptamer-based RNA switches or aptaswitches that recognize target nucleic acid molecules and initiate folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide an intense fluorescent readout without intervening enzymes, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment. Aptaswitches can be used to regulate folding of seven fluorogenic aptamers, providing a general means of controlling aptamers and an array of multiplexable reporter colors. Coupling isothermal amplification reactions with aptaswitches, we reach sensitivities down to 1 RNA copy/μL in one-pot reactions. Application of multiplexed all-in-one reactions against RNA from clinical saliva samples yields an overall accuracy of 96.67% for detection of SARS-CoV-2 in 30 minutes. Aptaswitches are thus versatile tools for nucleic acid detection that are readily integrated into rapid diagnostic assays.

UNASSIGNED: MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in healthy volunteers or in patients with psoriasis or rheumatoid arthritis (RA). This is the first study conducted under clinical practice conditions evaluating the switch from reference adalimumab to MSB11022 in patients with RA.
UNASSIGNED: Retrospective and multicenter study with data from the medical records of patients with RA who switched from reference adalimumab or another biosimilar to MSB11022 and maintained this treatment for at least 6 months. Information registered comes from baseline visit, the moment of the switch, and the follow-up visits.
UNASSIGNED: Data from 86 patients were evaluated (median age 63.5 years, 75.6% female, 44.2% had erosive RA). Only 3.5% of the patients received biologic therapy prior to adalimumab. At baseline, median DAS28-CRP was 1.77 (80.2% in remission and 96.5% with low disease activity) and median CDAI was 4.00 (44.2% in remission and 90.7% with low disease activity). After a median follow-up of 8 months, median DAS28-CRP was 1.87 (86.0% in remission and 94.2% with low disease activity) and median CDAI was 4.00 (38.5% in remission and 95.3% with low disease activity). Only three patients experienced pain, swelling, and stinging at the injection site or a locally extensive hematoma in the area of administration.
UNASSIGNED: Adalimumab biosimilar MSB11022 maintained the efficacy benefits provided by previous adalimumab treatments with a safety profile in line with that already described for other biosimilars.

Background: Adherence and persistence to treatment with disease-modifying therapies (DMTs) is a predictor of the efficacy of treatment. Aims: The objectives of the study were the analysis of adherence, persistence, switches, and costs of the drugs used in MS. Methods: This is a retrospective non-interventional pharmacological observational study of 610 patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) under therapy between January 2007 and September 2022. Results: Adherence values were greater than 0.75 for all the drugs in considered for the study. The mean persistence value was 2.5 years on the analysis performed on the first-line treatment. Conclusion: In a therapy in which adherence is predominant, but not exclusive to therapy efficacy, persistence to the drug is synonymous with drug efficacy.
Multiple Sclerosis (MS) is a chronic disease that often begins early in life. Like in many chronic diseases, consistent adherence to treatment is vital for the long-term effectiveness of therapies. In MS, most treatments—whether oral or parenteral—are self-administered at home, making long-term adherence crucial. Persistence in sticking with a single drug is also seen as an indicator of the treatment’s effectiveness, as longer use generally means fewer therapy changes and greater drug efficacy. This article analyzes these key pharmacy utilization metrics—adherence, persistence, and therapy switches—to directly compare the real-world effectiveness of the most commonly used MS drugs.

OBJECTIVE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept.
METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as \"good visual responders\" (≥ 5 letters from baseline) or \"poor visual responders\" (< 5 letters), and as \"good anatomical responders\" (any reduction in edema compared to baseline) or \"poor anatomical responders\" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab.
RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only \"poor visual responders\" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M =  + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with \"poor anatomical response\" upon transitioning exhibited a significant functional gain (Δswitch-6M =  + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05).
CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

The number of options for effective antiretroviral therapy (ART) is steadily increasing. Although older regimens may achieve the goal of virologic suppression, newer options can offer advantages in safety, tolerability, and convenience. In this article, we offer guiding principles for switching ART, highlighting reasons to pursue a switch and key factors to consider when selecting a new regimen.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has brought a significant reduction in HIV/AIDS-related morbidity and mortality. However, metabolic abnormalities (eg, dyslipidemias) have continued to pose significant challenges, warranting a switch between antiretroviral agents and/or the introduction of a statin. Hence, the purposes of this study was to compare the efficacy of switching between antiretroviral agents versus introducing a statin in the long-term management of HAART-induced dyslipidemia in people living with HIV, and to identify the most potent agent in switching therapies.
METHODS: A comprehensive literature search of PubMed and Medline identified articles published from the years 2000 to 2020 in the English language, resulting in 84 articles, 30 of which were selected based on inclusion and exclusion criteria. Information on primary and secondary outcomes was extracted. Statistical analysis was done on the variables, and the differences between groups were considered significant at P < 0.05.
RESULTS: Statin use was associated with significant reductions in triglycerides and total cholesterol (TC) at 6 weeks (both, P < 0.01). A switch of antiretroviral agents was associated with gradual reductions in TC and triglycerides for up to 48 weeks (both, P < 0.01). Statin use was associated with a reduced CD4 count at 24 weeks (P < 0.01). A switch of antiretroviral agents was associated with an increased CD4 count at 48 weeks (P < 0.01).
CONCLUSIONS: Statins were as effective as switching antiretroviral therapies in the short-term management of TC and triglycerides in patients with HAART-induced dyslipidemia.

Micro-Electro-Mechanical System (MEMS) switches have emerged as pivotal components in the realm of miniature electronic devices, promising unprecedented advancements in size, power consumption, and versatility. This literature review paper meticulously examines the key issues and challenges encountered in the development and application of MEMS switches. The comprehensive survey encompasses critical aspects such as material selection, fabrication intricacies, performance metrics including switching time and reliability, and the impact of these switches on diverse technological domains. The review critically analyzes the influence of design parameters, actuation mechanisms, and material properties on the performance of MEMS switches. Additionally, it explores recent advancements, breakthroughs, and innovative solutions proposed by researchers to address these challenges. The synthesis of the existing literature not only elucidates the current state of MEMS switch technology but also paves the way for future research avenues. The findings presented herein serve as a valuable resource for researchers, engineers, and technologists engaged in advancing MEMS switch technology, offering insights into the current landscape and guiding future endeavors in this rapidly evolving field.

UNASSIGNED: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA).
UNASSIGNED: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back.
UNASSIGNED: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed.
UNASSIGNED: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors.
UNASSIGNED: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.