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Background: Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut., Methods: We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein. For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment) was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence., Results: Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group (84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge. The primary analysis with prespecified multiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg. In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported., Conclusions: In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment. (Funded by the National Center for Advancing Translational Sciences [UL1TR004419] and the National Institute of Allergy and Infectious [U19AI136053]; ClinicalTrials.gov number, NCT03907397.).

Cancer genome alterations often lead to vulnerabilities that can be used to selectively target cancer cells. Various inhibitors of such synthetic lethal targets have been approved by the FDA or are in clinical trials, highlighting the potential of this approach 1-3 . Here we analysed large-scale CRISPR knockout screening data from the Cancer Dependency Map and identified a new synthetic lethal target, PELO, for two independent molecular subtypes of cancer: biallelic deletion of chromosomal region 9p21.3 or microsatellite instability-high (MSI-H). In 9p21.3-deleted cancers, PELO dependency emerges from biallelic deletion of the 9p21.3 gene FOCAD, a stabilizer of the superkiller complex (SKIc). In MSI-H cancers, PELO is required owing to MSI-H-associated mutations in TTC37 (also known as SKIC3), a critical component of the SKIc. We show that both cancer subtypes converge to destabilize the SKIc, which extracts mRNA from stalled ribosomes. In SKIc-deficient cells, PELO depletion induces the unfolded protein response, a stress response to accumulation of misfolded or unfolded nascent polypeptides. Together, our findings indicate PELO as a promising therapeutic target for a large patient population with cancers characterized as MSI-H with deleterious TTC37 mutations or with biallelic 9p21.3 deletions involving FOCAD., Competing Interests: Competing interests: S.R. holds equity in Amgen and receives research funding from Microsoft. J.R.P. is a paid consultant for ProFound Therapeutics. T.R.G. receives research funding from Calico Life Sciences and Deerfield Management, is a founder and equity holder of Sherlock Biosciences and Amplifyer Bio, and serves as a paid consultant and equity holder of Anji Pharmaceuticals and Dewpoint Therapeutics. C.D.C. serves as a paid consultant for Droplet Biosciences. J.M.D. is a consultant for and owns equity in Jumble Therapeutics. E.M.C. serves as a paid consultant for AbbVie, receives research support from Novartis and Genentech, and has received research support from Bayer. F.V. receives research support from the Dependency Map Consortium, Riva Therapeutics, Bristol Myers Squibb, Merck, Illumina and Deerfield Management. F.V. is on the scientific advisory board of GSK, is a consultant for and holds equity in Riva Therapeutics, and is a cofounder of and holds equity in Jumble Therapeutics. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Background: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates., Methods: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem., Results: We identified novel renin-expressing cholinergic neurons in the nucleus ambiguus (NuAm), a major vagal cardioinhibitory center in the brainstem. The expression of renin-angiotensin system genes was relatively abundant in the NuAm, implying that angiotensin II might mediate an important regulatory role in this nucleus and other regions with neural connectivity to the NuAm. Then, we generated conditional knockout mice lacking the classical renin isoform (Ren-a ChAT-KO ), specifically in cholinergic neurons. Ablation of Ren-a in cholinergic neurons abrogated renin expression in the NuAm. Moreover, studies using radiotelemetry, heart rate variability analyses, and pharmacological approaches revealed that the parasympathetic nervous system is depressed in Ren-a ChAT-KO males while augmented in the Ren-a ChAT-KO females. Subsequently, transcriptomic approaches were used to infer putative genes and signaling pathways regulated by renin within the NuAm., Conclusions: This study revealed that renin in cholinergic neurons plays a fundamental role in preserving autonomic balance and cardiovascular homeostasis in a sex-dependent manner. These findings define the NuAm as an endogenous, local source of renin with biological function and serve as conclusive evidence for the presence and functionality of the brain renin-angiotensin system., Competing Interests: None.

This study uses a biogeographic framework to identify patterns of gut microbiome divergence in an endangered lemur species endemic to Madagascar's southeastern rainforests, the Milne-Edwards's sifaka (Propithecus edwardsi). Specifically, we tested the effects of (1) geographic barriers, (2) habitat disturbance, and (3) geographic distance on gut microbiome alpha and beta diversity. We selected 10 social groups from 4 sites in Ranomafana National Park with varied histories of selective logging. Sites were spaced between 4 and 17 km apart falling on either side of two parallel barriers to animal movement: the Namorona River and the RN25 highway. Using 16S rRNA metabarcoding, we found the greatest beta diversity differentiation to occur between social groups, with significant divisions on opposite sides of geographic barriers (road/river). Habitat disturbance had the most significant effect on alpha diversity, though, contrary to many other studies, disturbance was associated with higher microbial species richness. Without biomedical context, it is unclear whether microbiome differences observed herein are neutral, adaptive, or maladaptive. However, microbiome divergence associated with the road/river may be a symptom of reduced host gene flow, warranting further investigation and perhaps conservation action (e.g., construction of wildlife bridges). Finally, this work demonstrates that significant microbiome variation can accrue over small sampling areas, lending new insight into host-microbe-environmental interactions., (© 2025 The Author(s). American Journal of Primatology published by Wiley Periodicals LLC.)

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of  alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments in this study were approved by the Institutional Animal Care and Use Committee (IACUC) of MSU, protocol #2022-158-95. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Plant mitochondrial and plastid genomes have exceptionally slow rates of sequence evolution, and recent work has identified an unusual member of the MutS gene family ("plant MSH1 ") as being instrumental in preventing point mutations in these genomes. However, the effects of disrupting MSH1 -mediated DNA repair on "germline" mutation rates have not been quantified. Here, we used Arabidopsis thaliana mutation accumulation (MA) lines to measure mutation rates in msh1 mutants and matched wild type (WT) controls. We detected 124 single nucleotide variants (SNVs: 49 mitochondrial and 75 plastid) and 668 small insertions and deletions (indels: 258 mitochondrial and 410 plastid) in msh1 MA lines. In striking contrast, we did not find any organelle mutations in the WT MA lines, and reanalysis of data from a much larger WT MA experiment also failed to detect any variants. The observed number of SNVs in the msh1 MA lines corresponds to estimated mutation rates of 6.1×10 -7 and 3.2 ×10 -6 per bp per generation in mitochondrial and plastid genomes, respectively. These rates exceed those of species known to have very high mitochondrial mutation rates (e.g., nematodes and fruit flies) by an order of magnitude or more and are on par with estimated rates in humans despite the generation times of A. thaliana being nearly 100-fold shorter. Therefore, disruption of a single plant-specific genetic factor in A. thaliana is sufficient to erase or even reverse the enormous difference in organelle mutation rates between plants and animals.

As one of the most threatened mammalian taxa, lemurs of Madagascar are facing unprecedented anthropogenic pressures. To address conservation imperatives such as this, researchers have increasingly relied on conservation genomics to identify populations of particular concern. However, many of these genomic approaches necessitate high-quality genomes. While the advent of next-generation sequencing technologies and the resulting reduction in associated costs have led to the proliferation of genomic data and high-quality reference genomes, global discrepancies in genomic sequencing capabilities often result in biological samples from biodiverse host countries being exported to facilities in the Global North, creating inequalities in access and training within genomic research. Here, we present the first published reference genome for the endangered red-fronted brown lemur ( Eulemur rufifrons ) from sequencing efforts conducted entirely within the host country using portable Oxford Nanopore sequencing. Using an archived E. rufifrons specimen, we conducted long-read, nanopore sequencing at the Centre ValBio Research Station near Ranomafana National Park, in rural Madagascar, generating over 750 Gb of sequencing data from 10 MinION flow cells. Exclusively using this long-read data, we assembled 2.157 gigabase, 2980-contig nuclear assembly with an N50 of 101.6 Mb and a 17,108 bp mitogenome. The nuclear assembly had 30× average coverage and was comparable in completeness to other primate reference genomes, with a 96.1% BUSCO completeness score for primate-specific genes. As the first published reference genome for E. rufifrons and the only annotated genome available for the speciose Eulemur genus, this resource will prove vital for conservation genomic studies while our efforts exhibit the potential of this protocol to address research inequalities and build genomic capacity., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gut microbiome and common mental disorders in European, North American, and Asian populations. As part of the saNeuroGut Initiative, we assessed associations between gut microbial composition and self-reported symptoms of anxiety, depression, and posttraumatic stress (PTS) among South African adults., Methods: Participants completed validated, online self-report questionnaires to evaluate symptoms of state anxiety, trait anxiety, depression, and PTSD. Eighty-six stool-derived microbial DNA samples underwent sequencing of the V4 region of the 16S rRNA gene to characterise gut bacterial taxa in the sample., Results: No significant associations were observed between symptom severity scores and alpha (Shannon and Simpson indices) and beta (Aitchison distances) diversity metrics. Linear regression models revealed that the abundances of Catenibacterium, Collinsella, and Holdemanella were significantly positively associated with the severity of PTS symptoms., Conclusion: Catenibacterium, Collinsella, and Holdemanella have each previously been associated with various psychiatric disorders, with Catenibacterium having been positively associated with symptoms of PTSD in another South African cohort. This study sheds light on the relationship between the human gut microbiome and symptoms of anxiety, depression, and PTS in a South African adult sample., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: This study investigated whether: 1) walking training (WT) changes cardiovascular load after walking until maximal intermittent claudication (IC) in patients with peripheral artery disease (PAD); and 2) acute and chronic cardiovascular responses to walking were related to each other., Methods: A randomized, controlled, parallel-group design was employed. Thirty-two men with PAD and IC were randomly assigned to one of two groups: WT (n=16) or control (CO, n=16) twice a week for 12 weeks. The WT group completed 15, 2-min bouts of walking at moderate intensity interspersed with 2-min upright resting intervals per session. The CO group completed 30 minutes of stretching per session. At Baseline and after 12 weeks, both groups underwent a progressive walking session to maximal IC (3.2 km/h, 2% increase in grade every 2 min). Systolic blood pressure (BP), diastolic BP, heart rate (HR), and rate pressure product (RPP) were measured pre- and post-walking. Data were analyzed by three-way mixed ANOVAs. Pearson correlations were used to explore the association between the acute and chronic responses., Results: WT significantly reduced pre- and post-walking systolic BP (p<0.001), diastolic BP (p<0.001), and RPP (p<0.001). No significant correlations were found between the acute and chronic changes observed for all variables (all p>0.05)., Conclusion: In patients with PAD, WT decreased cardiovascular load assessed before and after walking to maximal IC. Furthermore, the acute and chronic cardiovascular responses to walking were not associated. Thus, WT may reduce the risk of immediate post-walking cardiac events in susceptible patients., Competing Interests: Declaration of competing interest The authors declare that there's no financial/personal interest or belief that could affect our objectivity in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

The primary aim of this study was to evaluate the convergent validity of the Motor domain (MOT) of PediaTrac TM v3.0, an online developmental tracking instrument based on caregiver reports, with fine and gross motor domains (ASQ-FM and ASQ-GM) of the Ages and Stages Questionnaire (ASQ-3) in infants between 2- and 9 months of age. Participants were caregivers of 571 infants born term or preterm (gestational age <37 weeks) enrolled in a multi-site psychometric study of PediaTrac TM . Findings revealed significant correlations between MOT and ASQ-3 scores at 2, 4, 6, and 9 months across time periods, term-preterm status, and biological sex. A significantly higher percentage of infants born preterm, compared with those born at term, was identified as a moderate or high risk on both the ASQ-3 and PediaTrac. Future investigations are warranted to further examine the psychometric properties of the MOT domain, including sensitivity, specificity, and positive and negative predictive value., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gestational trophoblastic neoplasia (GTN) with spinal metastasis is rare with few documented cases worldwide. Few studies have explored chemotherapy combined with radiotherapy in the treatment of such cases. However, because of its rarity, there is still no standardized treatment regimen. A 34-year-old Gravida 1 Para 0 (0010) was diagnosed with GTN with metastasis to the lumbosacral spine, resulting in conus medullaris syndrome with lumbar radiculopathy. She presented with a 14-month history of amenorrhea, left lower extremity pain, and urinary and bowel retention. On examination, there was a 10.0 × 7.0 cm lumbosacral mass and atrophy of the left lower extremity. Transvaginal ultrasound showed a cul de sac mass, and diluted β-human chorionic gonadotropin (β-hCG) titer was markedly elevated at more than 1000 000 mIU/mL. Magnetic resonance imaging (MRI) of the lumbosacral spine showed an ill-defined sacral mass measuring 13.3 × 11.5 × 6.3 cm with spinal canal, bone, muscle, and nerve root involvement. She was treated with 10 cycles of EMACO and palliative radiotherapy with 10 sessions of 30 Gy of external beam radiation therapy directed toward the lumbosacral mass. Repeat MRI showed a decrease in size of the mass to 6.6 × 8.2 × 4.1 cm with concurrent decrease in β-hCG to 1.30 mIU/ml, and resolution of leg pain and urinary and bowel symptoms. She was declared to be in remission 3 months after the last cycle of EMACO., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: The American Medical Informatics Association (AMIA) Task Force on Diversity, Equity, and Inclusion (DEI) was established to address systemic racism and health disparities in biomedical and health informatics, aligning with AMIA's mission to transform healthcare. AMIA's DEI initiatives were spurred by member voices responding to police brutality and COVID-19's impact on Black/African American communities., Materials and Methods: The Task Force, consisting of 20 members across 3 groups aligned with AMIA's 2020-2025 Strategic Plan, met biweekly to develop DEI recommendations with the help of 16 additional volunteers. These recommendations were reviewed, prioritized, and presented to the AMIA Board of Directors for approval., Results: In 9 months, the Task Force (1) created a logic model to support workforce diversity and raise AMIA's DEI awareness, (2) conducted an environmental scan of other associations' DEI activities, (3) developed a DEI framework for AMIA meetings, (4) gathered member feedback, (5) cultivated DEI educational resources, (6) created a Board nominations and diversity session, (7) reviewed the Board's Strategic Planning for DEI alignment, (8) led a program to increase diversity at the 2020 AMIA Virtual Annual Symposium, and (9) standardized socially-assigned race and ethnicity data collection., Discussion: The Task Force proposed actionable recommendations that focused on AMIA's role in addressing systemic racism and health equity, helping the organization understand its member diversity., Conclusion: This work supported marginalized groups, broadened the research agenda, and positioned AMIA as a DEI leader while reinforcing the need for ongoing transformation within informatics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Objective: We identified factors associated with computed tomographic (CT) imaging within 24 hours of emergency department (ED) presentation in hospitalized children with severe orbital infections., Patients and Methods: A multicenter retrospective cohort study was conducted that included children aged 2 months to 18 years between 2009 and 2018 who were admitted to the hospital with severe orbital infections, including periorbital and orbital cellulitis. Multivariable modified Poisson regression was used to identify possible factors associated with receiving a CT scan within 24 hours of ED presentation., Results: Of 1144 children, 494 (43.2%) received a CT scan within 24 hours of ED presentation. Factors associated with receiving a CT scan within 24 hours included sex (male; adjusted relative risk [aRR], 1.18; 95% CI, 1.04-1.33), hospitalized at a children's hospital (aRR, 1.80; 95% CI, 1.32-2.45), consulted by both ophthalmology and otolaryngology (aRR, 3.12; 95% CI, 2.35-4.13) or either ophthalmology (aRR, 2.19; 95% CI, 1.66-2.90) or otolaryngology (aRR, 2.66; 95% CI, 1.84-3.86), and had proptosis (aRR, 1.39; 95% CI, 1.24-1.57) or eye swollen shut (aRR, 1.27; 95% CI, 1.13-1.43) as clinical signs upon ED presentation. Children aged younger than 5 years were less likely to receive early CT imaging (aRR, 0.63; 95% CI, 0.53-0.74). There were no associations between time of ED triage, temperature greater than 38 °C, or inflammatory markers with early CT imaging., Conclusion: Although several patient and hospital factors associated with early CT imaging decisions in children with severe orbital infections are associated with more severe infections, newly identified risk factors, such as inflammatory markers, were not. These findings will help better the understanding of clinical management and indications for CT imaging., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: To identify evidence syntheses of health interventions addressing racial health equity reporting the use of equity-focused frameworks and logic models., Study Design and Setting: The search strategy included three sources; a search of three bibliographic databases to identify systematic reviews assessing interventions to improve racial health equity, semistructured interviews with diverse group and a targeted organization website searches (eg, National Institute of Health, United States Preventive Services Task Force) to identify relevant logic models and frameworks. The searches were conducted between January 1, 2020, and January 25, 2023. We used a qualitative approach to identify and describe key characteristics of equity-focused logic models and frameworks used in evidence syntheses., Results: Of the 153 racial health equity-focused evidence syntheses identified, two explicitly used logic models to describe the intervention mechanism. We identified seven existing health equity frameworks from semistructured interviews and electronic search of key websites that were categorized by stated purpose as providing guidance for 1) research, 2) health policy, 3) digital health-care solutions, and 4) clinical preventive services. Two out of seven frameworks included guidance on integrating frameworks or logic models in evidence synthesis while the majority provided contextual information on how to define or consider race or racism as a structural determinant of health., Conclusion: There is limited use of logic models and frameworks in evidence syntheses addressing racial health equity. There is a need for more applied frameworks providing guidance for framing, conducting and interpreting findings of evidence syntheses addressing racial health equity., Plain Language Summary: The goal of this study was to find reviews of health programs that focus on improving racial health equity, and to see if they used special frameworks or models designed to address equity. To do this, we searched three major research databases, conducted interviews with a diverse group of people, and looked at relevant organization websites (like the National Institute of Health and the World Health Organization) between January 2020 and January 2023. We used a qualitative approach to study the key features of these equity-focused frameworks and models. We found 153 reviews focused on racial health equity, but only two of them used logic models to explain the intervention. From interviews and website searches, we identified seven existing health equity frameworks. These were grouped into four categories: research, health policy, digital health care, and clinical preventive services. Only two of these frameworks provided advice on how to use them in evidence reviews, while most focused on understanding how race and racism impact health as a social factor. In conclusion, there is limited use of frameworks and models in reviews about racial health equity. More practical frameworks are needed to help guide the research and interpretation of these reviews., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Trade-offs resulting from the high demand of offspring production are a central focus of many subdisciplines within the field of biology. Yet, despite the historical and current interest on this topic, large gaps in our understanding of whole-organism trade-offs that occur in reproducing individuals remain, particularly as it relates to the nuances associated with female reproduction. This volume of Integrative and Comparative Biology (ICB) contains a series of papers that focus on reviewing trade-offs from the female-centered perspective of biology (i.e., a perspective that places female reproductive biology at the center of the topic being investigated or discussed). These papers represent some of the work showcased during our symposium held at the 2024 meeting of the Society for Integrative and Comparative Biology (SICB) in Seattle, Washington. In this roundtable discussion, we use a question-and-answer format to capture the diverse perspectives and voices involved in our symposium. We hope that the dialogue featured in this discussion will be used to motivate researchers interested in understanding trade-offs in reproducing females and provide guidance on future research endeavors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Objective: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect a third of Australian adults, and its prevalence is predicted to rise, increasing the burden on the healthcare system. The LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD) trialled a community-based fibrosis assessment service using FibroScan to reduce the time to diagnosis of high-risk NAFLD and improve patient outcomes., Methods: We conducted a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD diagnosis and assessment. Participants had suspected NAFLD and were referred to a hepatology clinic in one of three major hospitals in South-East Queensland. Eligible consenting participants were randomised to receive usual care or the intervention (LOCATE). Participants in the intervention arm received a FibroScan outside of the hospital setting, with results provided to their primary care provider and the referring hepatologist. All participants were followed up 12 months after randomisation to measure their clinical and patient-reported outcomes., Results: 97 participants were recruited from October 2020 to December 2022. Of the 50 participants randomised to the intervention arm, one failed to attend their appointment, and of the 48 (98%) who had a FibroScan 13 (27%) had a liver stiffness measurement of 8.0 kPa or greater. The HR for the time to diagnosis of high risk was 1.28 (95% CI 0.59 to 2.79), indicating a faster average time to diagnosis with the intervention, but failing to conclusively demonstrate a faster time. The intervention did greatly reduce the time to FibroScan by almost 1 year (median difference 0.92 years, 95% CI 0.56 to 1.45). Other clinical outcomes showed minimal changes., Conclusion: The LOCATE model shows potential for impact, particularly in reducing waiting times for patients at high risk of developing severe liver disease due to NAFLD. A larger sample and longer follow-ups are needed to measure additional clinical outcomes., Trial Registration Number: ACTRN12620000158965., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The shift to competency-based education inspired reflection on using multiple-choice questions (MCQs) to develop and assess student competency. Student-authored MCQs in other fields demonstrate a higher level of knowledge; however, a gap examining the use of this teaching methodology in nurse practitioner education exists., Method: Nurse practitioner students created MCQs addressing content objectives. Faculty reviewed each MCQ's accuracy; students integrated feedback and revised questions. Finalized MCQs were posted in a question bank for examination preparation., Results: The question bank contained 112 questions covering 32 topics. Students demonstrated increasing success on these questions in subsequent examinations. Questions sometimes revealed content misunderstanding, which faculty addressed and clarified. Student surveys revealed interest in assignment integration in all courses., Conclusion: This assignment has progressed to a group project, and a competency-based rubric, mapped to the level 2 American Association of Colleges of Nursing's The Essentials: Core Competencies for Professional Nursing Education , was added. Using student-authored MCQs is a novel method to develop "knows how" competencies. [ J Nurs Educ . 2024;63(X):XXX-XXX.] .

The National Institute on Aging (NIA) plays a pivotal role in advancing scientific research, developing training and the science workforce, and promoting public health initiatives. However, the benefits of the NIA's work have not been equally distributed among all older adult population groups, highlighting persistent disparities in chronic illness burden and access to healthcare and research. As the NIA commemorates its 50th anniversary, this milestone presents an opportunity to reflect on its consequential initiatives and accomplishments while also strategizing for the robust inclusion of underrepresented and minoritized populations and the future health of our Nation's older adult population. Disparities in Alzheimer's disease and related dementias among four minoritized and racialized groups are highlighted, as well as the critical need to recruit and retain investigators from these populations. Three trans-NIA training, outreach, and pipeline initiatives are described as having elevated the profile of aging research across the nation, particularly among minoritized and ethnic groups, and have reached thousands of individuals interested in aging research. Leaders and healthcare advocates argue that efforts to reduce health disparities cannot be fully achieved without successfully addressing the underrepresentation of minoritized leaders in healthcare and research. Racism, xenophobia, discrimination, and separation deprive our nation and the scientific community of the breadth of talent, expertise, and perspectives needed to address racialized/minoritized health inequities. To all the staff at the NIA, past and present, may you continue to be proud of the work you do, the Institute you represent, and the difference you make. Happy 50th Anniversary!, (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Modeling studies of household transmission data have helped characterize the role of children in influenza and coronavirus disease 2019 (COVID-19) epidemics. However, estimates from these studies may be biased since they do not account for the heterogeneous nature of household contacts. Here, we quantified the impact of contact heterogeneity between household members on the estimation of child relative susceptibility and infectivity. We simulated epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like and influenza virus-like infections in a synthetic population of 1000 households, assuming heterogeneous contact levels. Relative contact frequencies were derived from a household contact study according to which contacts are more frequent in the father-mother pair, followed by the child-mother, child-child, and finally child-father pairs. Child susceptibility and infectivity were then estimated while accounting for heterogeneous contacts or not. When ignoring contact heterogeneity, child relative susceptibility was underestimated by approximately 20% in the two disease scenarios. Child relative infectivity was underestimated by 20% when children and adults had different infectivity levels. These results are sensitive to our assumptions of European-style household contact patterns; but they highlight that household studies collecting both disease and contact data are needed to assess the role of complex household contact behavior on disease transmission and improve estimation of key biological parameters., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To inform methods for centering racial health equity in syntheses, we explored (1) how syntheses that assess health-related interventions and explicitly address racial health inequities have engaged interest holders and (2) guidance for engaging racially and ethnically diverse interest holders., Study Design and Setting: We systematically identified evidence syntheses (searches limited to January 1, 2020, through January 25, 2023) and guidance documents (no search date limits) for this overview. From syntheses we extracted data on engagement rationale and processes and extracted approaches suggested from guidance documents. We summarized findings qualitatively., Results: Twenty-nine of the 157 (18%) eligible syntheses reported using engagement. Syntheses typically lacked robust detail on why and how to use and structure engagement and outcomes/effects of engagement, though syntheses involving Indigenous populations typically included more detail. When reported, engagement typically occurred in early and later synthesis phases. We did not identify guidance documents that specifically intended to provide guidance for engaging racially/ethnically diverse individuals in syntheses; some related guidance described broader equity considerations or engagement in general., Conclusion: This review highlights gaps in understanding of the use of engagement in racial health equity-focused syntheses and in guidance specifically addressing engaging racially and ethnically diverse populations. Syntheses and guidance materials we identified reported limited data addressing the whys, hows, and whats (ie, rationale for, approaches to, resources needed and effects of) of engagement, and we lack information for understanding whether engagement makes a difference to the conduct and findings of syntheses and when and how engagement of specific populations may contribute to centering racial health equity. A more informed understanding of these issues, facilitated by prospective and retrospective descriptions of engagement of diverse interest holders, may help advance actionable guidance and reviews., Plain Language Summary: We identified evidence syntheses (a kind of research that identifies and summarizes findings of individual studies or publications to address research questions) that looked at studies of interventions to improve differences in effects on health for racial or ethnic populations to see (1) if and how they incorporated perspectives of interest holders, people with an interest in the subject being studied; (2) what guidance for how to engage or involve racially or ethnically diverse interest holders exists. We found that 29 of 157 syntheses addressing interventions to improve differences in effects on health reported involving interest holders but typically did not provide much detail about how to involve people. Syntheses that involved Indigenous people usually had more information, but overall, the syntheses did not have much information about how to involve people and what the impact of involving them may be. We did not find guidance information that specifically set out to provide information about engaging racially/ethnically diverse individuals in syntheses; some related guidance described considerations about involving people in syntheses in general. This review highlights gaps in understanding of how to engage people in racial health equity-focused syntheses and in guidance specifically addressing engaging racially and ethnically diverse populations. Syntheses and guidance materials we identified reported limited information about whys, hows, and whats (ie, reasons to use, how to do, and resources needed and effects of) related to engagement, and we lack information to help understand whether engagement makes a difference in doing syntheses and when and how engagement of specific populations may help to address racial health equity., Competing Interests: Declaration of competing interest There are no competing interests for the authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Gait retraining, which typically focuses on the most severely affected limb or joint, has shown promising results in treating faulty running and walking patterns. The closed-chain nature of gait during the stance phase may influence kinematic changes in the adjacent joints of the trained leg. In addition, the coupled nature of the lower extremity motion of gait suggests that changes in one leg may transfer to the other. This study aimed to assess the intra- and inter-limb transfer of kinematic changes following gait retraining to reduce knee extension in individuals with hyperextension walking patterns., Methods: Seventeen women with knee hyperextension gait patterns participated in six treadmill retraining sessions. All participants received verbal and real-time visual kinematic feedback in the form of knowledge of results. This intervention study took place at the Gait Analysis Laboratory at the University of Iowa. Mean peak sagittal-plane lower extremity joint kinematics during overground walking at pretraining, post-training, and 1- and 8-month follow-ups were calculated for analysis and comparisons., Findings: The post-training changes in ankle range of motion returned to baseline values by the 8-month follow-up. There was a significant transfer effect of kinematic changes to the untrained knee following gait retraining., Interpretation: Training one knee did not result in long-term compensatory kinematic changes in the other joints. In addition, the improvements in knee extension range of motion were transferred to the untrained knee and retained at the 8-month follow-up. This study supports the use of gait retraining as an effective clinical intervention., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: In the context of profound and persistent racial health inequities, we sought to understand how to define racial health equity in the context of systematic reviews and how to staff, conduct, disseminate, sustain, and evaluate systematic reviews that address racial health equity., Study Design and Setting: The study consisted of virtual, semistructured interviews followed by structured coding and qualitative analyses using NVivo., Results: Twenty-nine individuals, primarily United States-based, including patients, community representatives, systematic reviewers, clinicians, guideline developers, primary researchers, and funders, participated in this study. These interest holders brought up systems of power, injustice, social determinants of health, and intersectionality when conceptualizing racial health equity. They also emphasized including community members with lived experience in review teams. They suggested making changes to systematic review scope, methods, and eligible evidence (such as adapting review methods to include racial health equity considerations in prioritizing topics for reviews, formulating key questions and searches, and specifying outcomes) and broadening evidence to include designs that address implementation and access. Interest holders noted that sustained efforts to center racial health equity in systematic reviews require resources, time, training, and demonstrating value to funders., Conclusion: Interest holders identified changes to the funding, staffing, conduct, dissemination, and implementation of systematic reviews to center racial health equity. Action on these steps requires clear standards for success, an evidence base to support transformative changes, and consensus among interest holders on the way forward., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Systematic reviews hold immense promise as tools to highlight evidence-based practices that can reduce or aim to eliminate racial health disparities. Currently, consensus on centering racial health equity in systematic reviews and other evidence synthesis products is lacking. Centering racial health equity implies concentrating or focusing attention on health equity in ways that bring attention to the perspectives or needs of groups that are typically marginalized., Study Design and Setting: This Cochrane US Network team and colleagues, with the guidance of a steering committee, sought to understand the views of varied interest holders through semistructured interviews and conducted evidence syntheses addressing (1) definitions of racial health equity, (2) logic models and frameworks to centering racial health equity, (3) interventions to reduce racial health inequities, and (4) interest holder engagement in evidence syntheses. Our methods and teams include a primarily American and Canadian lens; however, findings and insights derived from this work are applicable to any region in which racial or ethnic discrimination and disparities in care due to structural causes exist., Results: In this series, we explain why centering racial health equity matters and what gaps exist and may need to be prioritized. The interviews and systematic reviews identified numerous gaps to address racial health equity that require changes not merely to evidence synthesis practices but also to the underlying evidence ecosystem. These changes include increasing representation, establishing foundational guidance (on definitions and causal mechanisms and models, building a substantive evidence base on racial health equity, strengthening methods guidance, disseminating and implementing results, and sustaining new practices)., Conclusion: Centering racial health equity requires consensus on the part of key interest holders. As part of the next steps in building consensus, the manifold gaps identified by this series of papers need to be prioritized. Given the resource constraints, changes in norms around systematic reviews are most likely to occur when evidence-based standards for success are clearly established and the benefits of centering racial health equity are apparent., Plain Language Summary: Racial categories are not based on biology, but racism has negative biological effects. People from racial or ethnic minority groups have often been left out of research and ignored in systematic reviews. Systematic reviews often help clinicians and policymakers with evidence-based decisions. Centering racial health equity in systematic reviews will help clinicians and policymakers to improve outcomes for people from racial or ethnic minority groups. We conducted interviews and a series of four systematic reviews on definitions, logic models and frameworks, methods, interventions, and interest-holder engagement in syntheses. We found that much work remains to be done in centering racial health equity in systematic reviews. Specifically, systematic reviewers need to change who is represented on their teams, establish foundational guidance (on definitions and causal mechanisms and models, identify what interventions work to address racial health equity, strengthen method guidance, disseminate and implement results, and sustain new practices)., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To examine the predictability of categorical and quantitative study variables on acute stroke knowledge amongst study participants., Design: Non-experimental, descriptive correlational., Methods: A convenience sample of registered nurses caring for adult, hospitalized patients recruited from the urban Southeast. A three-part survey was emailed to the nurses: demographics, stroke education and experience, and the Acute Stroke Management Questionnaire., Results: Intensive Care Unit and Emergency Department nurses had the highest level of stroke knowledge. Nurses reporting three or more post-licensure education modalities had higher stroke knowledge scores than those reporting two or less. Practice setting, self-perception of stroke knowledge, self-identified knowledge of acute stroke management and three items related to code stroke were significantly correlated with stroke knowledge., Conclusion: Various methods of training and reinforcement of learning using varying teaching styles are effective in increasing nurses' stroke knowledge. Further stroke education is needed for nurses across the acute care setting., Implications: Future studies should explore lived experiences of nurses to gain understanding of nonquantifiable factors that nurses feel have strengthened their stroke knowledge., Impact: What Problem Did the Study Address? ○ Addressing the gap in the knowledge of predictors of nurse stroke knowledge. MAIN FINDINGS?: Practice setting, post-licensure stroke education, code stroke familiarity, confidence and understanding were all predictive of the overall stroke knowledge. WHOM WILL THE RESEARCH HAVE AN IMPACT?: Nurses, nurse educators, patients experiencing and at risk for stroke., Reporting Method: The STROBE checklist was used to strengthen the reporting of the results., Patient or Public Contribution: Nurses voluntarily participated in this study by completing the online questionnaire. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Provides predictors of stroke knowledge for nurse leaders to have a better understanding of nurses' educational needs. Provides evidence of a quick, effective measure of nurses' stroke knowledge., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Objectives: To systematically evaluate definitions of "racial health equity" (RHE) and related terms within health-related academic literature., Study Design and Setting: We systematically evaluated definitions of RHE and related terms within health-related academic articles. Articles published in English were included, and no date restrictions were imposed., Results: We found 20 original articles containing relevant definitions out of 1816 retrieved articles, thirteen of which were published from 2020 to 2023. Themes used in the definitions varied; racism (n = 12) and quality of healthcare (n = 10) were the most common. Additional themes, including social hierarchy or marginalization, discrimination, justice, unmet social needs, and historical events were described within some definitions. Eleven of the included manuscripts defined race as a social construct., Conclusion: This study depicts RHE as an emerging concept with limited consensus on racism, quality of health, and social determinants of health as important underlying frameworks. To center equity efforts and actions under a workable and shared vision, we recommend continued discussions regarding underlying meanings of RHE concepts and propose establishing a definition that promotes unity across health fields and prevents ambiguity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Joint position sense (JPS) is crucial for maintaining posture, protecting joints, and carrying out daily activities such as walking. Studies show that exercises to strengthen muscles and improve proprioception can positively impact JPS during passive and less complex activities. Evidence suggests that motor training can effectively enhance sensory function, including JPS, due to the extensive connections between the motor cortex and somatosensory areas. Gait retraining using real-time feedback has improved outcomes among patients with musculoskeletal disorders. The effect of gait retraining on JPS has not been investigated. This study assessed the effects of gait retraining to reduce knee extension in joint position sense in individuals with knee hyperextension walking patterns., Methods: Ten women with asymptomatic knee hyperextension (KH) >5° during overground walking participated in this study. Sagittal-plane kinematics were assessed using a three-dimensional (3D) motion analysis system. The JPS was assessed using the Knee Position Active Reproduction Test. The knee with the highest hyperextension was the focus of the gait retraining intervention, which consisted of six 1-h sessions using verbal instructions and visual kinematic feedback. Comparisons of peak knee extension during walking and knee JPS overall error (RMSE) were made using a paired t-test., Results: Gait retraining intervention significantly reduced knee extension angle during walking (83.8 % change; p < 0.001; Cohen's d = -1.6) and improved knee JPS (62 % change; p = 0.023; Cohen's d = 0.8) post-training. In addition, the improvements in joint kinematics (36.7 % change; p = 0.005; Cohen's d = -1.2) and JPS (52.6 % change; p = 0.015; Cohen's d = 0.9) were observed in the untrained knee., Significance: Gait retraining can improve joint position sense. This study addresses a gap in our understanding of how gait retraining can influence JPS. Our results corroborate that gait retraining is an evolving and promising strategy for improving gait outcomes, particularly in individuals with KH walking patterns., Competing Interests: Declaration of competing interest This study did not receive any specific grant from public, commercial, or not-for-profit funding agencies. The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

The study is a longitudinal review of pain management claims filed in the state of Maryland. Adverse outcomes associated with pain-related claims are often severe and include death, brain damage, and back and spinal cord sequelae. There is a lot to be learned from past experiences, identified in closed pain management claims, specifically on how to improve patient education, outcomes, quality, and safety., Competing Interests: Disclosure The authors have nothing to disclose. The views, analyses, and conclusions expressed in this article are those of the authors and do not necessarily reflect the official policy or positions of the American Association of Colleges of Nursing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: We aim to (1) evaluate the methods used in systematic reviews of interventions focused on racialized populations to improve racial health equity and (2) examine the types of interventions evaluated for advancing racial health equity in systematic reviews., Study Design and Setting: We searched MEDLINE, Cochrane, and Campbell databases for reviews evaluating interventions focused on racialized populations to mitigate racial health inequities, published from January 2020 to January 2023., Results: We analyzed 157 reviews on racialized populations. Only 22 (14%) reviews addressed racism's role in driving racial health inequities related to the review question. Eleven percent (7) of reviews considered intersectionality when conceptualizing racial inequities. Two-thirds (105, 67%) provided descriptive summaries of included studies rather than synthesizing them. Among those that quantified effect sizes, 54% (21) used biased synthesis methods like vote counting. The most common method assessed was tailoring interventions to meet the needs of racialized populations. Reviews mainly focused on assessing interventions to reduce racial disparities rather than enhancing structural opportunities for racialized populations., Conclusion: Reviews for racial health equity could be improved by enhancing methodologic quality, defining the role of racism in the question, using reliable analytical methods, and assessing process and implementation outcomes. More focus is needed on assessing structural interventions to improve opportunities for racialized populations and prioritize these issues in political and social agendas., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to examine the impact of a contact-free continuous monitoring system on clinical outcomes including unplanned intensive care unit (ICU) transfer (primary), length of stay (LOS), code blue, and mortality. A secondary aim was to evaluate the return on investment associated with implementing the contact-free continuous monitoring program during the COVID public health emergency., Methods: An interrupted time series evaluation was conducted to examine the association between the use of contact-free continuous monitoring and clinical outcomes. A cost-benefit analysis was planned to evaluate the return on investment., Results: Use of contact-free continuous monitoring was not significantly associated with unplanned ICU transfers, deaths, ICU LOS, and or rapid response team calls. However, there were significant increases in code blue events ( P  = 0.02) and mean hospital LOS ( P  = 0.01) in the postimplementation period when compared with the preimplementation period. Due to the lack of improvement, costs were calculated but a cost-benefit analysis was not conducted., Conclusions: Contact-free continuous monitoring bed use during the COVID-19 public health emergency was not associated with improvements in clinical outcomes, although there was substantial confounding. Future studies should include large randomized controlled trials to control for factors not under direct experimental control including unit staffing, staff turnover, and differences in the patient population related to surges in the COVID-19 pandemic., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections., Methods: Data were drawn from a surveillance study of households with children ( N  = 1913) recruited from 12 U.S. cities during the initial year of the pandemic and followed for 28 weeks (data collection: 1-May-2020 through 22-Feb-2021). Caregivers rated how much they worried about family members getting COVID-19 and subsequently reported household levels of outside-the-home social activities that could increase risk for SARS-CoV-2 transmission at 14 follow-ups. Caregivers collected household nasal swabs on a fortnightly basis and peripheral blood samples at study conclusion to monitor for SARS-CoV-2 infections by polymerase chain reaction and serology. Primary analyses used generalized linear and generalized mixed-effects modelling., Results: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with lower COVID-19 worry had higher odds of (a) reporting discretionary outside-the-home social interaction and (b) SARS-CoV-2 infection., Conclusions: This was, to our knowledge, the first study showing that caregiver COVID-19 illness worry was predictive of both COVID-19 mitigation compliance and laboratory-determined household infection. Findings should inform studies weighing the adaptive value of worrying about infectious disease outbreaks against established detrimental health effects., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Unlabelled TableAuthor InitialsRoyalties or LicensesConsulting FeesPayment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational eventsPayment for Expert testimonyStock or stock optionsPatents planned, issued or pendingReceipt of equipment, materials, drugs, medical writing, gifts or other servicesData Safety Monitoring Board MemberDJJAreteia, Avillion, AstraZeneca, GlaxoSmithKline, Genentech, Regeneron, and SanofiPfizerLBBElsevierSanofi, Regeneron, Genentech, GlaxoSmithKline, DBV technologies, Teva, Medscape, Kinaset, OM Pharma, AstraZeneca, and RecludixSanofi, Regeneron, GlaxoSmithKlineSanofi/RegeneronDBV Technologies, AstraZeneca, Vertex, AravaxMERUptoDate,Ception Therapeutics (Reslizumab), Mapi Trust (PEESS instrument)Bristol Myers Squibb,Regeneron/Sanofi,Astra Zeneca,Nexstone One,Celldex,Revolo Biotherapeutics,GuidepointTucker EllisPulm One,Spoon Guru,ClostraBio,Serpin Pharm,Allakos,Celldex,Nextstone One, Santa Ana BioEoE Diagnostic Panel; U.S. Patent 9,345,763MASSpeaker with Honoraria: Rutgers University, (Denver Allergy Rounds, National Jewish Health), Johns Hopkins University, Colorado Allergy and Asthma Society MeetingRGuptaGenentech, Novartis, Aimmune LLC, Allergenis LLC, Food Allergy Research & EducationPatent: Yobee (U.S. Patent No. 11,103,544)SJTUptoDate IncTVHSanofi, Infectious Diseases Respiratory ForumPfizerWPRegeneron, Sanofi, Genentech, Novartis, GSK, Astra Zeneca, (© 2024 The Authors.)

Objective: To evaluate modified versions of the Belimumab International Study in Lupus Nephritis (BLISS-LN) belimumab study primary efficacy renal response (mPERR) and complete renal response (mCRR) criteria (excluding mandatory corticosteroid tapering) as predictors of real-world, long-term renal outcomes among patients with lupus nephritis (LN)., Methods: This retrospective, observational study (GSK Study 212866) used deidentified data between 1970 and 2015 from the University of Toronto Lupus Cohort from adults diagnosed with systemic lupus erythematosus and biopsy-proven Class III±V, IV±V or V LN. At 24 months postbiopsy, patients were retrospectively indexed as responders/non-responders based on mPERR (estimated glomerular filtration rate (eGFR) ≤20% below biopsy value/≥60 mL/min/1.73 m 2 and urine protein:creatinine ratio (uPCR) ≤0.7 g/day) or mCRR (eGFR ≤10% below biopsy value/≥90 mL/min/1.73 m 2 and uPCR ≤0.5 g/day) criteria. The association between index mPERR (primary outcome) or mCRR (secondary outcome) status and long-term (up to 25 years, until censoring or death) renal survival (no progression to end-stage kidney disease (eGFR <30 mL/min/1.73 m 2 , dialysis or transplant) or death) was assessed., Results: Overall, 179 patients were included in the analysis (mPERR responders, n=128; non-mPERR responders, n=51). Most patients were female (87.2%); the mean (SD) age was 34.1 (11.3) years.Long-term renal survival was attained for 78.9% of mPERR responders and 60.8% of non-mPERR responders; achieving mPERR was associated with an increased likelihood of long-term renal survival versus not achieving mPERR (log-rank p=0.0119). Overall, 102 patients were mCRR responders, and 77 were non-mCRR responders. Long-term renal survival was attained for 80.4% of mCRR responders and 64.9% of non-mCRR responders; achieving mCRR was associated with an increased likelihood of long-term renal survival than not achieving mCRR (log-rank p=0.0259)., Conclusions: Achieving mPERR or mCRR was associated with improved long-term renal survival, highlighting that these statuses are suitable predictors of long-term renal outcomes in patients with LN., Competing Interests: Competing interests: MU has received grant/research support from GSK and consulting fees from GSK, UCB, Lilly and AstraZeneca, and has been a speaker for GSK, UCB, Lilly and AstraZeneca. ZT has received grant/research support from GSK and AZ and consulting fees from GSK, AbbVie, UCB and AstraZeneca, and has been a speaker for GSK, UCB and AstraZeneca. He has salary support from the Department of Medicine and holds the Dr MU Chair in Lupus Research at UHN. MEG, QF and RAL are employees of GSK and hold stock/shares in the company. PCJ was an employee of GSK at the time of the study and holds stock/shares in the company and is a current employee of RTI Health Solutions. KG was an employee of GSK at the time of the study and holds stocks and shares in GSK, and a current employee of AstraZeneca. JS, NA, JPDM and AM have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recently, the immunohistochemical markers cytokeratin 17 (CK17) and SRY-box2 (SOX2) have been evaluated as adjuncts for the diagnosis of high-grade vulvar intraepithelial neoplasia (VIN). In the present study, the aim was to assess CK17 and SOX2 expression in VIN by studying 150 vulvar lesions, originally reported as high-grade VIN and to assess the diagnostic accuracy., Methods: All slides (H&E, p16 INK4a , p53, Ki-67, CK17, and SOX2 stains) were independently assessed by six pathologists and the final diagnosis was reached in consensus meetings, as follows: 46 human papillomavirus (HPV)-independent VIN (including 30 p53 mutant and 16 p53 wild-type lesions), 58 high-grade squamous intraepithelial lesions (HSILs), 4 low-grade SILs (LSILs), 37 non-dysplastic lesions, and 5 lesions where the histology was inconclusive., Results: CK17 positivity was observed in 100% p53 wild-type HPV-independent VIN, compared to 73% p53 mutant HPV-independent VIN, 14% HSILs, 0% LSILs, and 24% non-dysplastic lesions. SOX2 positivity was observed in 13% p53 wild-type HPV-independent VIN, 43% p53 mutant HPV-independent VIN, 2% HSILs, 0% LSILs, and 3% non-dysplastic lesions. The highest diagnostic accuracy (89%) for HPV-independent VIN was obtained when combining p53 and CK17 immunohistochemistry. The addition of SOX2 did not further increase diagnostic accuracy., Conclusion: To conclude, aside from p53, both CK17 and SOX2 can be of value for reaching an accurate diagnosis of HPV-independent VIN.

Objective: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data., Methods: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission., Results: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs., Conclusions: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Junsang Yoo and Won Chul Cha reports disclose financial support from National Research Foundation of Korea (NRF). The results, discussion, and conclusion of this paper are independent of the funding source., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Child growth influences future health and learning. School readiness refers to a child's ability to meet developmental expectations at school entry. The association of early growth rate and patterns with school readiness remains unknown., Objective: To determine the association of child body mass index (BMI) growth with school readiness in a cohort of young children., Methods: A prospective cohort study (2015-2022) was conducted in children 0-6 years enrolled in the TARGet Kids! research network in Toronto, Canada. Two analytical approaches were used to measure growth using child weight and height/length data between 0 and 4 years: (i) age- and sex-standardised BMI (zBMI) growth rate per year using a piecewise linear model; and (ii) distinct zBMI trajectories using latent class mixed models. School readiness (4-6 years) was measured using teacher-completed Early Development Instrument (EDI). Robust Poisson models and marginal linear models using generalised estimating equations were used adjusting for confounders identified a priori., Results: In this study of 1077 children (mean age at EDI completion: 4.8 years; 52.6% male) with 6415 zBMI measurements, mean growth rate was 0.65 zBMI units/year (0-2 years) and -0.11 zBMI units/year (2-4 years). Two distinct zBMI trajectories were identified: the stable trajectory and the catch-up trajectory. There was insufficient evidence that zBMI growth rates (risk ratio 1.10, 95% confidence interval 0.78, 1.55 for 0-2 years; risk ratio 0.71, 95% confidence interval 0.32, 1.57 for 2-4 years) or trajectories (risk ratio 1.05, 95% confidence interval 0.82, 1.35, catch-up trajectory vs. stable trajectory) were associated with school readiness., Conclusions: No association was found between BMI growth and school readiness. School readiness may be more impacted by factors directly related to obesity or adiposity at the time of EDI measurement rather than growth., (© 2024 John Wiley & Sons Ltd.)

Introduction: Work-related musculoskeletal injuries are common in general surgeons, causing chronic pain and lost work. However, formal ergonomic curriculums in residency programs are rare. We aimed to assess the feasibility of an interprofessional educational approach to ergonomics in general surgery residents, in collaboration with occupational therapy (OT) students., Methods: General surgery residents completed a survey regarding musculoskeletal pain and ergonomics. OT students captured photos of trainees performing open and laparoscopic abdominal surgery over a 4-wk period. Rapid entire body assessment (REBA) and the rapid upper limb assessment were used to assess ergonomic efficiency and postural risk. Higher scores represent unfavorable posture and correlate with the need for ergonomic change., Results: There were 37/44 (84%) responses. Everyone reported some degree of pain related to surgery, most commonly neck pain (75%), shoulder (61%), and foot pain (53%). Most residents (66%) felt the pressure to perform surgery regardless of the pain. Ergonomic breaks directed by faculty were reported by less than 11% of residents. A total of 11 intraoperative observations were made by OT students of surgical trainees, with a mean rapid upper limb assessment score of 6.1 and a mean rapid entire body assessment score of 7.3. These scores demonstrated suboptimal posture with recommendations for prompt change., Conclusions: This study conveys a successful interprofessional educational approach to assessing surgical ergonomics in general surgery residents. Musculoskeletal symptoms and intraoperative ergonomic dysfunctions are prevalent among general surgery residents, without workplace measures for management or prevention. This needs assessment will be used to create an ergonomics initiative for the surgery residency., (Copyright © 2024. Published by Elsevier Inc.)

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics., (© 2024 Wiley Periodicals LLC.)

Introduction: Given the increasing incidence of chronic degenerative diseases related to changes in tissues, the availability of diagnostic tools with greater accuracy in the estimation of body composition (BC) has become necessary. Interpreting the BC values of individuals requires reference data obtained from a healthy population with the same ethnicity, to identify individuals at risk for the development of negative health outcomes., Objective: Generate reference values (RV) of body composition (BC) for Mexican children and adolescents., Methods: This was an urban-population-based cross-sectional study of healthy Mexican children and adolescents. BC estimations by anthropometry, multifrequency bioimpedance analysis (MF-BIA) and dual-energy X-ray absorptiometry (DXA) where used to create sex- and age-specific RV by means of generalized additive models for location, scale and shape (GAMLSS)., Results: We assessed 2104 subjects, and after confirming a clinically and metabolically healthy status, we measured 1659 subjects aged 5-20 years, [806 females (49%) and 853 males (51%)] by anthropometry, MF-BIA and DXA to create sex- and age- smoothed reference centiles, lambda (L), mu (M), and sigma (S) values. We also built sex- and age-smoothed graphic curves for each variable of interest., Conclusions: We present valid RV and curves for BC variables estimated by anthropometry, MF-BIA and DXA from clinically and metabolically healthy urban Mexican children and adolescents. These RV are different from those reported for other populations, and therefore, should be used for clinical and research purposes involving urban Mexican children and adolescents., (© 2023. The Author(s).)

Background: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells., Methods: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis., Results: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance., Conclusion: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: High-quality trial evidence supports the use of one dose of dexamethasone in the outpatient management of croup; however, there are no inpatient trials, and the optimal treatment regimen for the inpatient management of croup remains uncertain. Significant practice variability exists in the corticosteroid treatment of children hospitalized for croup., Objective: To evaluate the association of dexamethasone treatment regimen (1 vs. >1 dose) with hospital length of stay (LOS) and 30-day return to emergency department (ED) visits among children hospitalized for croup., Methods: A cohort study of children hospitalized for croup at a children's hospital between 2010 and 2022. Children less than 10 years old, without known airway anomalies and who received dexamethasone for croup treatment were included. Children who received 1 dose versus >1 dose of dexamethasone were compared. Propensity score analyses, using inverse probability of treatment weighting, were conducted to estimate the treatment effects of dexamethasone regimen on hospital LOS and all-cause 30-day return to ED visit., Results: Of 471 children hospitalized for croup, 229 (49%) received 1 dose of dexamethasone; 242 (51%) received >1 dose. In the propensity-weighted analyses, children receiving >1 dose of dexamethasone had a longer mean LOS by 59.6 h (95% CI 44.8-74.5, p < .001) compared with those receiving >1 dose. There was no statistically significant difference in the odds of all-cause 30-day return to ED visit; OR 1.30, (95% CI 0.76-2.22, p = .33)., Conclusions: Among children hospitalized for croup, children who received >1 dose of dexamethasone had a longer LOS compared with children who received 1 dose of dexamethasone; however, there was no statistically significant difference in the 30-day return to ED visits. Randomized clinical trials are needed to determine the optimal dexamethasone treatment regimen for children hospitalized with croup., (© 2024 The Author(s). Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Background: Accurate identification of incident venous thromboembolism (VTE) for quality improvement and health services research is challenging. The purpose of this study was to evaluate the performance of a novel incident VTE phenotyping algorithm defined using standard terminologies, requiring three key indicators documented in the electronic health record (EHR): VTE diagnostic code, VTE-related imaging procedure code, and anticoagulant medication code., Methods: Retrospective chart reviews were conducted to assess the performance of the algorithm using a random sample of phenotype(+) and phenotype(-) diagnostic encounters from primary care practices and acute care sites affiliated with five hospitals across a large integrated care delivery system in Massachusetts. The performance of the algorithm was evaluated by calculating the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, using the phenotype(+) and phenotype(-) diagnostic encounters sample and target population data., Results: Based on gold-standard manual chart review, the algorithm had a PPV of 95.2 % (95 % CI: 93.1-96.8 %), NPV of 97.1 % (95 % CI: 95.3-98.4 %), sensitivity of 91.7 % (95 % CI: 90.8-92.6 %), and specificity of 98.4 % (95 % CI: 98.1-98.6 %). The algorithm systematically misclassified a low number of specific types of encounters, highlighting potential areas for improvement., Conclusions: This novel phenotyping algorithm offers an accurate approach for identifying incident VTE in general populations using EHR data and standard terminologies, and accurately identifies the specific encounter and date of diagnosis of the incident VTE. This approach can be used for measurement of incident VTE to drive quality improvement, research to expand the evidence, and development of quality metrics and clinical decision support to improve the diagnostic process., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Biosampling studies in critically ill patients traditionally involve bedside collection of samples followed by local processing (ie. centrifugation, aliquotting, and freezing) and storage. However, community hospitals, which care for the majority of Canadian patients, often lack the infrastructure for local processing and storage of specimens. A potential solution is a "simplified" biosampling protocol whereby blood samples are collected at the bedside and then shipped to a central site for processing and storage. One potential limitation of this approach is that delayed processing may alter sample characteristics., Objective: To determine whether delays in blood sample processing affect the stability of cytokines (IL-6, TNF, IL-10, IFN-γ), chemokines (IL-8, IP-10, MCP-1, MCP-4, MIP-1α, MIP-1β), cell-free DNA (cfDNA) (released by dying cells), and blood clotting potential in human blood samples., Methods: Venous blood was collected into EDTA and citrate sample tubes and stored at room temperature (RT) or 4°C for progressive intervals up to 72 hours, prior to processing. Plasma cytokines and chemokines were quantified using single or multiplex immunoassays. cfDNA was measured using Picogreen DNA Quantification. Blood clotting potential was measured using a thrombin generation assay., Results: Blood samples were collected from 9 intensive care unit (ICU) patients and 7 healthy volunteers. Admission diagnoses for the ICU patients included sepsis, trauma, ruptured abdominal aortic aneurysm, intracranial hemorrhage, gastrointestinal bleed, and hyperkalemia. After pre-processing delays of up to 72 hours at RT or 4°C, no significant changes were observed in plasma cytokines, chemokines, cfDNA, or thrombin formation., Conclusions: Delayed sample processing for up to 72 hours at either RT or 4°C did not significantly affect cytokines, chemokines, cfDNA, or blood clotting potential in plasma samples from healthy volunteers and ICU patients. A "simplified" biosampling protocol is a feasible solution for conducting biosampling research at hospitals without local processing capacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gyorffy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX)., Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included., Primary Endpoint: proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets., Results: The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO., Conclusions: BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted., Trial Registration Number: NCT03312907., Competing Interests: Competing interests: CA has received research support from GSK; consulting fees from GSK, AstraZeneca, BMS, Kezar Life Sciences Inc., Merck Sharp & Dohme and Alumis Inc. CFA has received research support from Janssen, AbbVie, and Eli Lilly. ZA has received research support from GSK, Roche, AstraZeneca, and Amgen; and consulting fees from GSK, AstraZeneca, Amgen, Kezar Life Sciences Inc, and Novartis. INB has received research support from Genzyme, Sanofi, and GSK; consulting fees from AstraZeneca, Eli Lilly, Aurinia Pharmaceuticals, GSK, and ILTOO; and has served as an advisory board member for AstraZeneca and Merck Serono. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). PCC has received consulting and speaker fees from GSK, Aurinia Pharmaceuticals, and Eli Lilly. WWC has received research support from GSK, UCB, Amgen, Pfizer, and BMS; consulting fees from GSK and Aurinia Pharmaceuticals; honoraria from GSK and Aurinia Pharmaceuticals for disease awareness presentations and curricula on achieving disease control and remission in SLE. RF has received research support and consulting fees from GSK. MBU has received research support from GSK; consulting fees from GSK and UCB; and speaker fees from GSK, Eli Lilly, and AstraZeneca. RvV has received research support for educational programmes and institutional grants from AstraZeneca, Pfizer, and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio; speaker fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, and UCB; and research support from BMS, GSK Eli Lilly, and UCB. RBH, AvM, JCO-A, MO and DAR are employees of GSK and hold stocks and shares in the company. RBH is also an inventor for the following patents: US-20220195062-A1, US-11180569-B2, and US-20180265588-A1. KLC, JG, MD, YIG, DS and PPT were employees of GSK at the time of the study and hold stocks and shares in the company. NLF is a former employee and consultant for GSK and holds stocks in the company. YOT has received unrestricted research grants from GSK, Aurinia Pharmaceuticals, and Vifor Pharma; and consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, Kezar Life Sciences Inc, Vifor Pharma, and Otsuka Pharmaceuticals (paid to Leiden University Medical Center)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: Conducting simulation testing with end-users is essential for facilitating successful implementation of new health information technologies. This study designed a standardized simulation testing process with a system prototype prior to implementation to help study teams identify the system's interpretability and feasibility from the end-user perspective and to effectively integrate new innovations into real-world clinical settings and workflows., Materials and Methods: A clinical simulation model was developed to test a new Clinical Decision Support (CDS) system outside of the clinical environment while maintaining high fidelity. A web-based CDS prototype, the "CONCERN Smart Application," which leverages clinical data to measure and express a patient's risk of deterioration on a 3-level scale ("low," "moderate," or "high"), and audiovisual-integrated materials, were used to lead simulation sessions., Results: A total of 6 simulation sessions with 17 nurses were held to investigate how nurses interact with the CONCERN Smart application and how it influences their critical thinking, and clinical responses. Four themes were extracted from the simulation debriefing sessions and used to inform implementation strategies. The strategies include how the CDS should be improved for practical real-world use., Discussion and Conclusions: Standardized simulation testing procedures identified and informed the necessary CDS improvements, the enhancements needed for real-world use, and the training requirements to effectively prepare end-users for system go-live., Competing Interests: Authors have no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Introduction: Limited evidence exists that clinical trial treatment response criteria predict long-term outcomes in Asian patients with lupus nephritis (LN)., Methods: This retrospective analysis of prospectively collected data from the Hong Kong Queen Mary Hospital Cohort categorized adults with biopsy-proven LN (Class III, IV, V, or mixed [III ± V, IV ± V]) after standard treatment for 2 years postbiopsy and immunosuppression induction according to modified primary efficacy renal response (mPERR: estimated glomerular filtration rate [eGFR] ≥ 60 ml/min per 1.73 m 2 or ≤ 20% below biopsy value AND urine protein-to-creatinine ratio [uPCR] ≤ 0.7) and modified complete renal response (mCRR; eGFR ≥ 90 ml/min per 1.73 m 2 or ≤ 10% below biopsy value AND uPCR ≤ 0.5). Associations between 2-year mPERR/mCRR status and long-term kidney survival and mild chronic kidney disease (CKD) or worse (stage ≥ 3) were assessed., Results: Of the 176 Chinese patients, 64.2% achieved mPERR and 43.8% achieved mCRR at 2 years postbiopsy. After mean follow-up of 15.3 years, significantly higher proportions of mPERR and mCRR responders versus nonresponders achieved long-term kidney survival (mPERR: 85.8% vs. 71.4%; P  = 0.029; mCRR: 92.2% vs. 71.7%; P  < 0.001). mPERR and mCRR achievement was associated with adjusted risk reductions for kidney nonsurvival of 60% ( P  = 0.034) and 86% ( P  < 0.001), respectively. Adjusted risk for mild CKD or worse (stage ≥ 3) was 82% ( P  = 0.013) and 87% ( P  = 0.012) lower for mPERR and mCRR responders, respectively, versus nonresponders., Conclusion: In Chinese patients with LN, mPERR and mCRR at 2 years postbiopsy predict superior long-term kidney outcomes and lower CKD progression risk., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)