Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients

BackgroundImmunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings.AimThis study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra®, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile.ResultsResults support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidatedConclusionsThis study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients’ quality of life.

Nudging and boosting children’s restaurant menus for healthier food choice: a blinded quasi-randomized controlled trial in a real life setting

Background Restaurants are ideal settings for implementing food interventions targeted at children. Studies with adults suggest that changes to the physical menu can lead to healthier food choices; online studies with parents indicate that specific menu designs facilitate healthier choices. However, it is unknown whether applying well-established nudging and boosting methods to children’s menus also increases their choice of healthier meals in a real-world restaurant setting. Methods The effects of two versions of a restaurant menu on the frequency of choosing a healthy meal (newly created, healthy target dish) were tested in a blinded quasi-randomized controlled trial. The menu in the control condition contained all dishes (including the healthy target dish) in a standardized format. The intervention menu included nudging (e.g. comic character, fun attractive name for the dish) and boosting elements (e.g. information on low calorie density) next to the healthy target dish. Over five months, the control and intervention menus were switched every two weeks and records were made of how often the healthy target dish was ordered. Results In total, 607 orders were made from the children’s restaurant menu (57% from the intervention menu). During the intervention phase, 4.2% of all ordered dishes from the children’s menu were the healthy target dish, during the control phase, 4.4% of orders were for the target dish (p=.896). Conclusions Contrary to our hypothesis, a modified children’s menu did not lead to a significant increase in the number of orders for a healthy dish compared with a neutral control menu. Importantly, given that parents and children often choose the child’s dish together, particularly boosting methods that focus on social processes and joint decision making could be promising to increase children’s frequency of healthy food choices in restaurants. Trial registration DRKS00027039, registered on 11/22/2021, (Retrospectively registered).

Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis

Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≤ 2 after a 9–14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.

Pharmacokinetic Evaluation of Eltrombopag in ITP Pediatric Patients

Background: Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, approved for refractory primary immune thrombocytopenia (ITP) in pediatric patients. In two pediatric RCTs, EPAG led to an improvement of platelet counts and a reduction in bleeding severity. However, a significant number of pediatric patients did not achieve the primary endpoints. We performed a pharmacokinetic evaluation of EPAG in pediatric patients with refractory ITP.Methods: Outpatients aged from 1 to 17 y, affected by refractory ITP to first-line treatment, were enrolled for a pharmacokinetic assessment. The analysis of drug plasma concentration was performed by the LC-MS/MS platform. Non-compartmental and statistical subgroup analyses were carried out using the R package ncappc.Results: Among 36 patients eligible for PK analysis, the median dose of EPAG given once daily was 50 mg. The EPAG peak occurs between 2 and 4 h with a population Cmax and AUC 0–24 geo-mean of 23, 38 μg/ml, and 275, 4 µg*h/mL, respectively. The pharmacokinetic profile of EPAG did not show a dose proportionality. Female patients showed a statistically significant increase of dose-normalized exposure parameters, increasing by 110 and 123% for Cmax and AUC 0–24, respectively, when compared to male patients. Patients aged 1–5 y showed values increased by more than 100% considering both exposure parameters, compared to older children. Furthermore, patients presenting complete response (83%), showed augmented EPAG exposure parameters compared to subjects with partial or no response.Conclusion: These data highlight the need to further explore the variability of EPAG exposure and its pharmacokinetic/pharmacodynamic profile in pediatric patients also in a real-life setting.

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009–2011) and 30.6% (2018–2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018–2019 vs. 2009–2011 was found (non-squamous: HR: 0.95 CI95%: 0.92–0.98; squamous: HR: 0.94 CI95%: 0.90–0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed.

Effect of Implicit Theory on Effort Allocation Strategies in Multiple Task-Choice Situations: An Investigation From a Socio-Ecological Perspective

Implicit theories refer to two assumptions that people make about the malleability of one’s ability. Previous studies have argued that incremental theorists (who believe that ability is malleable) are more adaptive than entity theorists (who believe that ability is fixed) when facing achievement setbacks. In the present research, we assumed that the adaptive implicit theory would be different when people could choose from a wider range of tasks. It was hypothesized that incremental theorists would sustain their efforts in the first task even when it was difficult, whereas entity theorists would try to find the most appropriate task. In a pair of laboratory experiments, participants had to maximize their outcomes when allowed to choose a task to engage in, from two options. When participants were allowed to practice the two tasks (Study 1), incremental theorists tended to allocate their effort solely to the first task, whereas entity theorists tended to put equal effort into both. When participants were informed that they could switch from the assigned task (Study 2), incremental theorists tended to persist in the first task regardless of its difficulty, whereas entity theorists tended to switch more quickly if the task was difficult. These results supported our hypothesis of two effort allocation strategies and implied that, in certain situations, entity theorists could be more adaptive than incremental theorists. Based on these findings, we conducted a social survey on the difficulty of switching tasks with a real-life setting as an environmental factor that determines the adaptive implicit theory (Study 3). It was revealed that the academic performance of incremental and entity theorists was moderated by the difficulty of switching tasks in their learning environment at school. Cultural differences in implicit theories may be explained by differences in the difficulty of switching tasks in education and career choices in each society.

Digital Mobility Assessment for Regulatory and Clinical Endorsement in Hip Fracture Patients

Hip fracture is the most frequent non-intentional injury of older persons leading to hospital admission in Europe and North America. Until recently, in regulatory submissions no attention was given to patients’ mobility after sustaining/recovering from a hip fracture. To better evaluate efficacy and effectiveness of new drugs and treatments, it is necessary to develop mobility biomarkers since failure to recover and regain pre-fracture mobility is considered the single most important disability symptom experienced by hip fracture patients, often leading to care home admission. However, regularly used measures of mobility capacity are not representative of individuals’ performance in real life, intermittent in nature, and require visiting study centers. Digital technology has the potential to revolutionize mobility assessment in a real-life setting. With this presentation we build a case for a valid solution for real-world digital mobility assessment in hip fracture patients as carried out in the “Mobilise-D” clinical validation study.

Applications of Wearable Technology in a Real-Life Setting in People with Knee Osteoarthritis: A Systematic Scoping Review

With the growing number of people affected by osteoarthritis, wearable technology may enable the provision of care outside a traditional clinical setting and thus transform how healthcare is delivered for this patient group. Here, we mapped the available empirical evidence on the utilization of wearable technology in a real-world setting in people with knee osteoarthritis. From an analysis of 68 studies, we found that the use of accelerometers for physical activity assessment is the most prevalent mode of use of wearable technology in this population. We identify low technical complexity and cost, ability to connect with a healthcare professional, and consistency in the analysis of the data as the most critical facilitators for the feasibility of using wearable technology in a real-world setting. To fully realize the clinical potential of wearable technology for people with knee osteoarthritis, this review highlights the need for more research employing wearables for information sharing and treatment, increased inter-study consistency through standardization and improved reporting, and increased representation of vulnerable populations.