Efficacy and safety of rituximab biosimilars or reference product as first‐line treatment in patients with low‐tumour‐burden follicular lymphoma: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Efficacy and safety of rituximab biosimilars or reference product as first‐line treatment in patients with low‐tumour‐burden follicular lymphoma: A systematic review and meta‐analysis via Journal of Clinical Pharmacy and Therapeutics Follicular lymphoma is a subtype of B-cell Non-Hodgkin lymphoma and is the second most common lymphoma diagnosed in the United States and Western Europe. The role of rituximab in the first-line treatment of low-tumour-burden follicular lymphoma has been supported by a large number of data. However, whether rituximab biosimilars have the same efficacy and safety as the reference drug (MabThera) is still controversial. Electronic databases and the ClinicalTrail.gov website were extensively searched using relevant search criteria. Studies were screened according to inclusion and exclusion criteria. Then the risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. Finally, four clinical randomized controlled trials involving 1223 patients were included. There were no statistically significant differences in efficacy and safety between biosimilars and MabThera groups. Our study concluded that the efficacy and safety of rituximab biosimilars in the treatment of low-tumour-burden follicular lymphoma are highly similar to those of the original drug. Abstract What is Known and Objective The role of rituximab in the first-line treatment of low-tumour-burden follicular lymphoma (LTB-FL) has been supported by a large number of data. However, whether rituximab biosimilars have the same efficacy and safety as the reference drug (MabThera) is still controversial. Methods Electronic databases and the ClinicalTrail.gov website were extensively searched using relevant search criteria. The risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. Results and Discussion A total of 1223 patients were included in four clinical randomized controlled trials. There was no statistical difference in efficacy between biosimilars and MabThera groups (the objective response rate: RR = 1.00, 95% CI: 0.93–1.08, p = 0.92; the progression-free survival: RR = 1.04, 95% CI: 0.96–1.12, p = 0.30; the overall survival: RR = 1.00, 95% CI: 0.98–1.03, p = 0.76; the serious adverse events: RR = 1.15, 95% CI: 0.69–1.89, p = 0.59; the infusion-related reaction: RR = 0.91, 95% CI: 0.77–1.09, p = 0.32). In terms of safety, there was also no significant difference between two groups. What is New and Conclusion Our study concluded that the efficacy and safety of rituximab biosimilars in the treatment of LTB-FL are highly similar to those of the original drug. View on Web

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Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy

alexandrossfakianakis shared this article with you from Inoreader Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy via Neuro-Oncology Advance Access Abstract Background Ultra-high dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising anti-tumor efficacy compared to conventional dose rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes. Methods Cohorts of three-week-old male and female C57Bl/6 mice exposed to hypofractionated (2×10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months post-treatment. Animals were sacrificed 6 months post-irradiation and tissues analyzed for neurological and cerebrovascular decrements. Results The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neuroco gnitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin) and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and a preservation of cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels. Conclusions Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlight its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefit s of FLASH-RT that extend from synapse to cognition and the microvasculature. View on Web

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Performance of Existing and Novel Symptom- and Antigen Testing–Based COVID-19 Case Definitions in a Community Setting

alexandrossfakianakis shared this article with you from Inoreader Performance of Existing and Novel Symptom- and Antigen Testing–Based COVID-19 Case Definitions in a Community Setting via American Journal of Epidemiology - Advance Access Abstract Point-of-care antigen tests are an important tool for SARS-CoV-2 detection yet are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this analysis was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.53 for antige n testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and our code is publicly available to aid public health practitioners in developing or fine-tuning their own case definitions. View on Web

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Medical body modification in youth with gender dysphoria or body dysmorphic disorder – is current practice coherent and evidence‐based?

alexandrossfakianakis shared this article with you from Inoreader Editorial Perspective: Medical body modification in youth with gender dysphoria or body dysmorphic disorder – is current practice coherent and evidence‐based? via Journal of Child Psychology and Psychiatry In recent decades, there has been a steady increase in the number of people, including adolescents, undergoing medical body modification (MBM) to alter their physically healthy bodies in invasive and nearly irreversible ways through medical treatment (e.g. surgery). While MBM is often recommended for youth with persisting gender dysphoria (GD), in body dysmorphic disorder (BDD) it has been considered contraindicated. Here, we outline the current controversies surrounding MBM practice and recommendations in adolescents with GD versus those with BDD in order to better understand under what circumstances we may or may not support adolescents who want to change their bodies medically and often irreversibly. We compare the two disorders in terms of the overlap and uniqueness of their behavioural and psychological features. In doing so, we discuss limitations of the existing (often low-quality) evidence for and against MBM in young patients. We conclude that the c urrently available evidence is too preliminary and far from conclusive to make any robust recommendations in terms of benefits and harms of MBM in youth with persisting GD or BDD. However, we strongly recommend further urgent scientific discussions and systematic research efforts into more robust evaluations and the identification of more precise psychological characteristics that may serve as decision criteria for or against MBM – particularly in those adolescents who did not respond to non-MBM, that is, psychiatric/psychological treatment and psychosocial support, if available at all. This will greatly benefit youth healthcare professionals in their challenging clinical practice of making decisions regarding MBM today and in the future. View on Web

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Polygenic risk scores for prediction of breast cancer

alexandrossfakianakis shared this article with you from Inoreader Polygenic risk scores for prediction of breast cancer in Korean women via International Journal of Epidemiology - Advance Access Abstract Background Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited. Methods We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS. Results< /div>All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS. Conclusions Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women. View on Web

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Testing different sources of environmental unpredictability on adolescent functioning: ancestral cue versus statistical learning and the role of temperament

alexandrossfakianakis shared this article with you from Inoreader Testing different sources of environmental unpredictability on adolescent functioning: ancestral cue versus statistical learning and the role of temperament via Journal of Child Psychology and Psychiatry Background The dimensional model of environmental adversity highlighted the effects of an unpredictable environment in promoting risky development. Toward gaining greater specificity in understanding, this multimethod, longitudinal study investigated the role of two sources of environmental unpredictability—ancestral cues versus statistical learning, and their interaction with dove temperament conceptualized within the evolutionary model of temperament, in shaping adolescent functioning. Methods Participants were 192 families with an adolescent (M age = 12.4) followed for two annual waves. We measured unpredictability within the ancestral-cue approach as incidents of disruptive family events, and statistical-learning unpredictability as the random variability in observed moment-to-moment maternal hostility during parent–child interaction. We focused on dove temperament, which characterizes strategies of cautious and inhibited behavior in novel contexts and persistence and intrinsic engagement in benign contexts. Results Findings indicated unique effects of ancestral-cue versus statistical-learning unpredictability—in interaction with dove temperament—in association with adolescent functioning. Ancestral-cue unpredictability interacted with dove temperament in association with vagal stress reactivity, and the interactive effects of statistical-learning unpredictability were only associated with set-shifting. Furthermore, the family instability-x-dove temperament interaction was linked to adolescent adjustment via vagal reactivity. Adolescents with lower dove temperament showed dampened vagal reactivity within the more unpredictable environments, which was in turn associated with a greater decrease in social withdrawal over time. Conclusions The findings highlighted the specificity in different sources of environmental unpredictability in shaping adolescent development. View on Web

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Update of the classification of midpalatal suture behaviour after surgically assisted rapid maxillary expansion using computed tomography

alexandrossfakianakis shared this article with you from Inoreader Update of the classification of midpalatal suture behaviour after surgically assisted rapid maxillary expansion using computed tomography via International Journal of Oral and Maxillofacial Surgery via MedWorm.com The aim of this study was to update the midpalatal suture classification after surgically assisted rapid maxillary expansion (SARME) using computed tomography (CT). Thirty-five patients with a transverse maxillary deficiency and unilateral or bilateral posterior crossbite underwent SARME with osteotomy of the pterygoid apophysis of the sphenoid. CT was performed before installation of the Hyrax expander appliance and after the final activation. Opening of the midpalatal suture was classified into three types: type I, total midpalatal suture opening from anterior nasal spine (ANS) to posterior nasal spine (PNS); type II, partial midpalatal suture opening from ANS to the transverse palatine suture, with partial or non-existent opening of the midpalatal suture posterior to the transverse pala... View on Web

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