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Venous thromboembolism (VTE) in children is a rare condition. It encompasses different clinical scenarios that require an individualized and multidisciplinary approach. The aim of this document is to provide a practical guideline for the management of pediatric VTE based on the best available evidence. An exhaustive literature review was performed, gathering information from current clinical guidelines and recent studies. This document compiles the recommendations on the diagnosis and treatment of VTE in infants, children, and adolescents endorsed by the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Thrombosis and Hemostasis (SETH), and the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Neonatal VTE, arterial thrombosis, and superficial venous thrombosis are beyond the scope of this work. This document includes a list of definitions aimed at standardizing terminology and another two distinct sections: (1) particularities of treatment, including recommendations regarding dosing, monitoring and cautions in the pediatric population, and (2) particularities in management, including specific recommendations for the most frequent scenarios in children.

A universal method of examining patterns of biodiversity on islands is the species-area relationship (SAR). SARs quantify the relationship between species richness (the number of species) and the area of the land mass on which they occur. An extension of the SAR, the speciation-area relationship (SpAR), quantifies the relationship between speciation rate and area. Comparing these relationships across island systems globally is a difficult task because gathering and processing a large amount of species occurrence and island data often requires researchers to conduct lengthy literature searches and combine datasets from several different sources. We present ssarp (Species-/Speciation-Area Relationship Projector), an R package that provides a systematic workflow for curating data, estimating speciation rates, and inferring SARs and SpARs. The ssarp workflow allows users to generate SARs and SpARs using either occurrence records or presence-absence matrices. Functions in ssarp use mapping tools to associate GPS points with land masses, remove points not on land, associate land masses with their areas using a built-in dataset of island names and areas, and infer SARs using unsegmented and segmented regression. The accuracy of these records can also be assessed by the user through the creation of a presence-absence matrix from ssarp's workflow. The ssarp R package also provides functions for estimating speciation rates and generating a SpAR. The ssarp R package allows researchers to increase the scope of their biodiversity research by efficiently inferring SARs and SpARs with occurrence records and presence-absence matrices.

The impact of COVID-19 containment policies (e.g., physical distancing, school closures) on population anxiety has been debated and difficult to resolve. To estimate the joint effects of state-level COVID-19 containment policies on anxiety symptoms during the early pandemic. Retrospective analysis of a prospective cohort with cross-sectional outcome assessment. All of Us Research Program, a U.S. national research cohort. 40,610 adult participants who completed the All of Us COPE survey in July 2020. Seven state-level COVID-19 containment policies (school closures, workplace closures, cancellation of public events, restrictions on gatherings, public transport closures, stay-at-home requirements, and restrictions on internal movement) measured from March 22 to May 23, 2020, via the Oxford COVID-19 Government Response Tracker (OxCGRT). The primary outcome was anxiety symptoms (GAD-7) in July 2020. Using quantile g-computation, we classified policies as anxiety-increasing or anxiety-decreasing by the sign of their training-set contributions, then re-estimated joint effects in a holdout testing set. Among participants (64% female; mean age: 57.8 years), 13.3% (n=5398) reported moderate-to-severe anxiety (GAD-7 score 10-21) in July 2020. The joint effect of all seven containment policies was not significant (β = 1.88, 95% CI: -0.51 to 4.28, p = 0.12). An anxiety-increasing joint effect from 4 policies (school, workplace, public events, internal movement; β = 2.98, 95% CI: 0.30 to 5.66, p = 0.03) and an anxiety-decreasing joint effect from 3 policies (gatherings, public transport, stay-at-home; β = -1.10, 95% CI: -1.75 to -0.44, p = 0.002) reached significance. Effects were largest in adults 18-44 (anxiety-increasing β = 8.93, 95% CI: 1.50 to 16.37, p = 0.02; anxiety-decreasing β = -2.81, 95% CI: -4.98 to -0.64, p = 0.01), with no significant effects in adults 45 and older. Modeling seven containment policies jointly showed no net anxiety effect, a result that masked opposing-direction effects. Partitioning by effect direction revealed significant joint effects exceeding single-policy estimates, with young-adult point estimates above the 4-point GAD-7 minimal clinically important difference (MCID) though lower CI bounds fell below it. These findings may inform the use of containment policies in future pandemics, given their differing association with population anxiety.

Metabolically-dysfunction-associated steatotic liver disease is today rising in prevalence among children and adolescents with obesity. The present Systematic Review and Meta-analysis explores the effect of weight loss interventions, depending on their modality (lifestyle, bariatric surgery or anti-obesity medication) on circulating, imagery-related and histology-related liver parameters in children and adolescents with obesity (aged 5-18 years). After consultation of the main databases (MEDLINE, EMBASE, Web of Science and Google Scholar and the Cochrane Controlled Register of Trials), 145 studies were included, gathering 18609 participants (10539 included in the meta-analysis) allocated to 257 experimental arms (26 diet, 24 medication, 96 multidisciplinary, 39 controls, 16 physical activity, 41 supplementation and 15 surgery). Circulating levels of liver enzymes were found improved in the large majority of the studies (most of them relying on multidisciplinary treatments), with however a lack of positive effect of physical activity programs. Sixty-seven percent of the intervention arms found significant improvements in hepatic fat, with no effect of physical activity interventions according to the meta-analysis. Bariatric Surgery appears as the only modality to improve histology-related parameters. According to the meta-regression, improvements in the Non-alcoholic fatty liver disease Activity Score are associated with the degree of weight loss and Body Mass Index reduction. The present results indicate improved overall liver status in response to weight loss interventions in this population, further studies remain however needed to clarify the effects of physical activity alone. Importantly, results also suggest the necessity to provide adapted and appropriate dietary and multidisciplinary interventions as first line strategies for liver-related health, especially in the context of obesity medication.

Long COVID is an emerging public health concern with heterogeneous prevalence. Evidence on the impact of reinfection and vaccination remains limited, especially in Spain. We conducted a prospective online cohort survey between January 2024 and April 2025, gathering data on demographics, vaccination, symptoms, comorbidities, and reinfection history from Spanish adults (n=1018). Long COVID was defined per NICE guidelines as symptoms persisting beyond eight weeks after viral clearance. Multivariate logistic regression identified associated factors. Of 972 participants (332 men, 640 women), long COVID prevalence was 14.3% (n=139). Female sex (OR: 1.70; 95% CI: 1.10-2.57; p=0.014) and chronic obstructive pulmonary disease (COPD) (OR: 4.14; 95% CI: 1.28-13.42; p=0.018) increased risk. Mixed vaccination schedules raised risk compared to Pfizer-only regimens (OR: 1.30; 95% CI: 1.04-1.62; p=0.020). Reinfection, reported by 47.2%, was also a risk factor (OR: 1.64; 95% CI: 1.12-2.42; p=0.012). Frequent long COVID symptoms included anosmia, dyspnea, pneumonia, and myalgia. This national cohort underscores the persistent burden of long COVID in Spain. Female sex, COPD, reinfection, and mixed vaccination schedules are key associated factors, with implications for targeted prevention strategies and vaccination policies.

The AAEV (American Association of Extracellular Vesicles) Annual Meeting at the John P. McGovern Commons in Houston, TX convened over 300 leading researchers, clinicians, and industry experts from around the world to advance the rapidly evolving field of extracellular vesicle (EV) science. EVs, nanoscale lipid-bound particles released by all prokaryotic and eukaryotic cells, have emerged as crucial mediators of intercellular communication, trans- porting proteins, nucleic acids, and lipids that influence a wide spectrum of physiological and pathological processes. Their involvement in immune modulation, tissue regeneration, cancer progression, metabolic regulation, and other complex biological functions positions EVs as promising diagnostic biomarkers and therapeutic delivery agents in precision medicine and personalized healthcare. However, significant challenges persist, including the heterogeneity of EV populations, complexities in isolation and purification, and the pressing need for standardized characterization protocols. The 2024 AAEV's annual gathering provided a pivotal forum for exchanging insights and cultivating collaborations. The meeting featured keynote addresses delved into the intricate heterogeneity, biogenesis pathways, and immu- nomodulatory capabilities of EVs, as well as their contributions to disease progression. Subsequent sessions covered a broad range of topics, showcasing cutting-edge technologies for EV isolation and characterization, revealing novel mechanisms by which EVs modulate immune responses and disease states, and presenting innovative EV engineering approaches for delivering therapeutics. Industry presentations complemented academic discussions by introducing scalable EV production systems, automated isolation methods, specialized analytical tools, and strategies to navigate regulatory pathways. Alongside these presentations, the association supports dissemination of the latest discoveries and methodologies through its flagship publication, Extracellular Vesicle (EV). Collectively, the insights shared at the AAEV Annual Meeting underscored the remarkable progress in understanding EV complexity, refining isolation and analysis techniques and translating fundamental discoveries into clinically actionable solutions. Speakers highlighted advanced isolation platforms, refined bioengineering methods, and efforts to integrate EV-based diagnostics and therapeutics into existing clinical frameworks. As the field matures, the forward momentum reflects a transition from theoretical potential to tangible applications. By fostering global collaboration, strengthening ties between academia and industry, and providing platforms like the EV journal, for ongoing dialogue, the EV community is well-positioned to surmount current challenges and accelerate the integration of EV-based approaches into mainstream healthcare.

A major marker of cryoinjury is intracellular ice formation (IIF), and its prevention is a key design goal of a successful cryopreservation protocol. Visualization and automated image analysis of IIF will be helpful in gathering data for understanding the mechanisms of the freezing process. There is a need for high-quality frozen-cell images and a tool to quantify IIF for investigating the effects of various cryopreservation protocol parameters. Here, we report the development of a freeze-substitution-based method for light microscopy imaging of cryopreserved endothelial cell monolayers and an automated ice detection algorithm for high-throughput analysis of visible intracellular ice crystals in the nuclei of cells within the captured images. Our method detected ice crystals ≥1.10 ± 0.28 μm in the frozen-cell images and yielded comparable accuracy in ice detection to that achieved by manual counting. This study describes a tool for the identification and quantification of IIF visible under light microscopy.

Pathogen diagnosis in rodents through effective health monitoring programs is essential for maintaining high welfare and standards in laboratory animal facilities. Although many animal facilities are increasingly adopting real-time polymerase chain reaction testing of environmental or filter samples for pathogen detection, thereby reducing the need for sentinel animals, classical methods such as microbiological assays and microscopic examination for parasites, remain essential and relevant tools in laboratory animal diagnostics. This article describes protocols for the identification of bacterial, viral, and parasitic agents in mice and rats in accordance with the recommendations of the Federation of European Laboratory Animal Science Associations. The methodologies presented detailed procedures for sample collection from mice and rats and for screening these samples using bacterial, parasitological, and viral panels. In addition, we describe bacterial culture techniques and the use of selective and differential media for pathogen isolation, as well as step-by-step protocols for the detection of pinworms, mites, and parasite eggs. These protocols provide a practical foundation for establishing a basic diagnostic laboratory to support standardized animal husbandry and health monitoring quality. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Gathering rodent samples for pathogen screening Basic Protocol 2: Inoculation and screening of bacterial cultures from rodent samples Support Protocol 1: Identification of bacteria using differential media Basic Protocol 3: Identification of Helicobacter by PCR targeting the 16S rRNA gene Basic Protocol 4: Pinworm screening by microscopy Support Protocol 2: Confirmation and specification of parasites (pinworms and mites) by PCR Basic Protocol 5: Mite screening by microscopy Basic Protocol 6: Virus identification by serology.

Climate hazards pose a threat to health and health services throughout Africa. They directly affect the primary care provider's clinic operations and patient morbidities like vector-borne and heat-related illnesses. Within a community-orientated primary care approach, primary care providers can assist communities to evaluate their vulnerabilities and capacities and identify the key risks. This article is based on a participatory action reflection (PAR) process (reflection, planning, action, observation of action) conducted by the author in Matsaudi Village, Botswana. A small village community on the edge of the Okavango Delta. Under reflection in the PAR cycle, several steps are described: (1) community and stakeholder engagement, (2) information gathering, (3) identification of vulnerabilities, capacities and risks through workshops on exposure to climate hazards, institutional assets, and the pathways from hazards to health and social effects. The process led to an action plan with both short- and long-term prioritised solutions. This stepwise template from Matsaudi Village enables primary health care providers to sustainably build climate-resilient communities.

Decentralized clinical trials (DCTs) represent an emerging model in clinical research, accelerated by the restrictions imposed during the COVID-19 pandemic. By leveraging digital technologies and local health care resources, DCTs aim to increase accessibility and reduce participant burden compared to traditional site-based models, which often face recruitment failures and high attrition rates. While various regulatory initiatives in Europe, such as the Accelerating Clinical Trials in the European Union program and the European Medicines Regulatory Network recommendation paper (updated in October 2025), have sought to facilitate their implementation, the widespread adoption of DCTs remains limited due to significant operational, regulatory, and technological challenges, including platform fragmentation and gaps in digital literacy. This study aimed to identify and prioritize actionable solutions to the main challenges of DCT implementation in Europe from a multistakeholder perspective, gathering insights to address specific ethical, legal, and operational barriers. Building on a preceding strengths, weaknesses, opportunities, and threats analysis, a 2-round Delphi study was conducted, involving 26 experts in clinical trials, ethics, law, regulation, and patient engagement between March and May 2023. In the first round, 309 open-ended responses were collected via REDCap (Research Electronic Data Capture; Vanderbilt University) surveys and underwent systematic inductive content analysis using ATLAS.ti (ATLAS.ti Scientific Software Development GmbH) with independent double coding. This process resulted in 244 unique proposals that were categorized according to 6 key challenges. In the second round, 39 synthesized proposals were evaluated using a 4-point Likert scale. Consensus was defined as ≥80% agreement on the appropriateness of each proposal. High levels of consensus were achieved, with 32 out of the 39 proposals reaching the threshold and 14 achieving 100% unanimity. Overall, 82% of the proposals were rated as "appropriate" or "very appropriate." Key recommendations included providing support and training for health care professionals, enhancing investigational medicinal product and biological sample logistics through validated technologies, improving collaboration with local health care providers, fostering regulatory harmonization while respecting national specificities, strengthening capacity-building initiatives, and promoting accessible, user-friendly digital tools supported by hybrid trial models. Conversely, proposals such as peer-to-peer participant support and the centralization of ethics reviews at the European Union level failed to reach consensus. The study offers a prioritized compilation of expert-driven recommendations for overcoming current barriers to DCT implementation in Europe. The adoption of these recommendations could support the development of more inclusive, efficient, and sustainable decentralized research frameworks across diverse health care systems.

Nanocomposite gel scaffolds is a promising technique for bone reconstructing in maxillofacial and orthopedic surgeries with the advantage of minimizing invasiveness and donor site morbidity. This review examines the potential of nanofiber hydrogels as scaffolds for bone regeneration and angiogenesis in critical-size defects based on histomorphometric and immunohistochemistry analysis while carefully considering the need for optimizing it with digital spatial transcriptomics in future bone research. Various scientific databases such as PubMed, Web of Science, ProQuest, and Embase were searched for pre-clinical studies published between 2000 and 2025, which focused on effects of bone regeneration and angiogenesis based on immunohistochemistry. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for gathering data. The ARRIVE checklist and Funnel plot analysis were utilized to evaluate the quality of the included studies. A meta-analysis was conducted to identify the true effects and biases involved in various studies. Twenty five articles were included for quantitative analysis. The pooled standardized mean difference (SMD = 4.52, 95% CI [3.29, 5.75]) strongly favors the experimental group indicating a significant improvement in bone regeneration outcomes. The diversity of methodologies and scaffold compositions used, showcases the broad applicability of these advanced biomaterials across different animal models supporting regeneration of bone. While immunohistochemistry is an established tool in its discoveries in skeletal defects, spatial transcriptomics has started its evolution as a cornerstone technology for future research in bone disorders.

Intimate partner violence (IPV) is a significant public health concern, affecting over 41% of women in the United States during their lifetime. IPV is particularly prevalent during reproductive years, including pregnancy and postpartum periods, and has severe adverse effects on both maternal and child health. Home visiting offers a promising context for prevention; however, persistent barriers to screening underscore the need for practical, implementation-ready tools to support home visitors in addressing IPV. This brief report describes a quality improvement initiative examining the implementation of the Futures Without Violence Connected Parents, Connected Kids (CPCK) cards within Alabama home visiting programs. Between September and December 2024, four Alabama local implementing agencies (LIAs) participated in the Home Visiting Collaborative Innovation and Improvement Network's (HV CoIIN) Sprint to Sustain Improvement in IPV (sprint). The sprint aimed to integrate CPCK cards into home visits, with a goal of educating 90% of families on healthy relationships and improving support for home visitors in discussing IPV. Data from Alabama's home visiting database were used to track IPV screening rates before and after the sprint. In addition, a survey was conducted to gather home visitors' perspectives on CPCK cards. Results showed that by the end of the sprint, all caregivers were educated about healthy relationships, and IPV screening rates improved at three LIAs and remained 100% at the fourth. Survey responses indicated that CPCK cards were valuable tools for facilitating conversations about healthy relationships and screening for IPV.

Predicting health outcomes from electronic health records (EHRs) is challenging because traditional models rely on structured data and often ignore external medical knowledge. We propose an approach that integrates structured EHR with text-based clinical evidence to improve prediction and interpretability. We introduce PHO-Agents, a multi-agent system powered by large language models (LLMs) for health outcome prediction. Structured EHR sequences are encoded to produce attention-based representations and initial logits, which are converted into patient summaries by a data agent. A retrieval agent gathers relevant clinical guidelines. Research and practical doctor agents independently assess the patient, and a leader agent synthesizes their analyses. Outputs from the EHR-based model and the LLM agents are fused to generate final predictions and explanation reports. PHO-Agents was evaluated on three real-world cohorts: acute kidney injury (AKI) patients (in-hospital mortality), chronic kidney disease patients (AKI onset within two years), and cancer patients receiving immune checkpoint inhibitors (immune-related adverse events within one year). PHO-Agents outperformed single-agent and multi-agent LLM baselines across all cohorts. In the AKI mortality task, it achieved a PR-AUC of 90.20 ± 2.07, compared with 56.46 ± 2.98 for the best single-agent baseline. Similar gains were observed in the ICI and CKD cohorts. Ablation studies showed that both multi-agent reasoning and logit-level fusion contributed to performance improvements, and case analyses demonstrated clinically consistent explanations. PHO-Agents integrates longitudinal EHR modeling with collaborative LLM reasoning, improving predictive performance, interpretability, and robustness across diverse clinical tasks. This hybrid approach offers a trustworthy strategy for real-world clinical decision support.

Pathogenic variants in COL1A1 and COL1A2 account for 85-90% of osteogenesis imperfecta (OI). Glycine substitutions within the triple-helical domain are traditionally considered highly pathogenic. The COL1A2 c.2827G>A p.(Gly943Arg) variant was previously classified as pathogenic under ACGS 2019/2020 criteria. One proband with this heterozygous variant was identified through national newborn genomic screening prompting further evaluation from the UK National OI Reference Laboratory. Four additional patients with the same variant were identified through referral to tertiary metabolic bone services/ Genetics clinic and phenotypic data were gathered to understand better clinical presentations and inheritance patterns. The variant was reassessed following the release of gnomAD v4.1, incorporating updated ACGS 2024 criteria. The expanded gnomAD v4.1 dataset incorporating UK Biobank (UKBB) demonstrated the presence of p.(Gly943Arg) in an unselected population at a frequency inconsistent with the pathogenicity of COL1A2, resulting in reclassification from pathogenic to variant of uncertain significance (VUS). Clinical presentations of 5 patients ranged from no fracture history to moderately severe OI. Cascade testing revealed multiple asymptomatic adult heterozygotes. UKBB data demonstrated no recorded OI diagnoses among 44 adult heterozygotes with evidence of a shared common haplotype in 40/45 enriched in Northwest England. The COL1A2 p.Gly943Arg variant demonstrates marked clinical heterogeneity and population frequency inconsistent with a fully penetrant dominant OI allele. This study highlights the dynamic nature of variant classification, the importance of large population datasets, and the ethical and clinical challenges of variant reclassification in the era of genomic screening.

The Climate Change Anxiety Scale (CCAS), developed by Clayton and Karazsia (2020), assesses the negative emotional impact of climate change on well-being. However, its psychometric properties have not yet been sufficiently explored for Spanish spoken in Spain and Spanish culture. This research introduces the Spanish version of the CCAS (CCAS-S), examines its psychometric properties, and provides validity evidence supporting its intended purpose. Two studies were conducted: first, the original version of the CCAS was translated into Spanish using a committee approach to translation design; second, 806 participants completed the CCAS-S along with additional assessment instruments to gather validity evidence. The 13-item Spanish version showed adequate reliability and internal structure validity evidence for the two-dimensional model, aligning with theoretical expectations. Nevertheless, a refined 10-item version distinguishing metacognitive impairment, emotional distress, and functional interference dimensions optimized the scale's intended purpose. The study discusses the conditions for using the CCAS-S measures and its practical implications.

Papillary thyroid carcer (PTC) is the most prevalent endocrine malignancy, with the morbidity increase in recent years. The presence of metastatic lymph nodes stands as a significant predictor for recurrent occurrences of the disease. In this study, we explored the utility of biomarkers in aiding the identification of lymph node metastases in patients with PTC. We gathered 388 formalin-fixed paraffin embedded (FFPE) lymph node specimens from 266 individuals who had undergone surgical procedures for PTC. These samples were analyzed for the mRNA expression level of thyroglobulin (TG), TSH receptor (TSHR), and sodium-iodide symporter (NIS) using the real-time fluorescence quantitative PCR (qPCR) method. The results were compared with pathologic diagnosis. Among 134 confirmed lymph node metastasis tissues, it was found that 123 samples expressed TG mRNA, 118 samples expressed TSHR mRNA and only 16 samples expressed NIS mRNA. Among 254 nonmetastatic lymph node tissues, 240 samples did not express TG mRNA, 219 samples did not express TSHR mRNA and 230 samples did not express NIS mRNA. The findings suggest that the measure of TG mRNA for the diagnosis of lymph node metastasis has a 91.79% sensitivity rate and a 94.49% specificity rate. The detection of TSHR mRNA displays an 88.06% sensitivity and an 86.22% specificity for recognizing lymph node metastasis. However, mRNA expression of NIS was not detected in most of lymph node samples. The research suggests that identifying TG mRNA expression in lymph nodes could serve as an effective approach to aid in postoperative diagnosing lymph node metastasis in patients with PTC.

The purpose of this guideline is to provide an evidence-based framework for healthcare professionals to recognize, manage, and prevent iron deficiency and iron deficiency anemia across the lifecycle of women, with particular emphasis on time periods of vulnerability, such as pregnancy, menstruation, and perioperatively. This clinical practice guideline seeks to improve the lives of women at all reproductive life stages, from menarche to menopause, with iron deficiency and iron deficiency anemia in the context of obstetrical and gynaecologic care. This guideline reviews the available options for the prevention, assessment, and treatment of iron deficiency and iron deficiency anemia. While the focus of this guideline pertains to oral and intravenous iron replacement therapy, the importance of reducing menstrual blood loss is also emphasized. By consolidating the best evidence to date with expert opinion across the disciplines of obstetrics and gynaecology, hematology, and anaesthesiology, we provide recommendations and treatment algorithms to guide the diagnosis and treatment of iron deficiency and iron deficiency anemia for patients within our specialty. The prevention, early identification, and treatment of iron deficiency and iron deficiency anemia is assessed to be a cost-effective strategy to improve the health and well-being of women of reproductive age. This proactive approach to iron deficiency and iron deficiency anemia has also been shown to reduce the need for blood transfusion, along with the associated harms and costs of transfusion. The potential costs of iron infusion therapy must be assessed in the context of the profound adverse impacts on quality of life, reduced work performance and decreased economic productivity of patients with iron deficiency and iron deficiency anemia. Using relevant MeSH headings and keywords (related to concepts of anemia, iron deficiency, blood management, blood conservation, transfusion, obstetrics, pregnancy, postpartum, and gynaecology), published literature was retrieved through searches of PubMed and Cochrane Systematic Reviews from January 2015 to December 2025. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. This guideline was developed through consensus by a multidisciplinary team of authors with representation from obstetrics, gynaecology, anaesthesiology, and hematology. The content and recommendations were drafted and agreed upon by the authors. The SOGC's Clinical Obstetrics and Gynaecology Committee reviewed the guideline and the Guideline Management and Oversight Committee approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. See online Appendix A (Tables A1 for definitions and A2 for interpretations). A national panel of patient partners was gathered to provide feedback and perspective on the recommendations and summary statements for this guideline. Community partners were purposefully selected to ensure representation of Canadian geographic regions, lived experience with iron deficiency or iron deficiency anemia, as well as obstetrical or gynaecologic care received. Healthcare providers involved in the assessment and management of women with iron deficiency and iron deficiency anemia. Iron deficiency (ID) and iron deficiency anemia (IDA) have profound impacts on the quality of life in women worldwide. As such, the early identification of ID/IDA and iron replacement therapy is an important strategy for women's health and wellbeing. General Principles of Diagnosis and Treatment GYNAECOLOGY: PRECONCEPTION, PREGNANCY, AND POSTPARTUM: RECOMMENDATIONS: General Principles of Diagnosis and Treatment GYNAECOLOGY: PRECONCEPTION, PREGNANCY, AND POSTPARTUM.

Recommendations from the American Board of Pediatrics propose a two-year fellowship for Neonatal-Perinatal Medicine. A survey of members of the Association of Academic Neonatology Division Directors was conducted to gather perspectives on the recommendations. A minority of respondents were supportive of 2-year fellowships. Although there may be some financial benefit by transitioning to a faculty salary earlier, risk of burnout, attrition of the academic and physician scientist pipeline, and curtailing innovation and discovery were cited as major concerns. Division directors are supportive of enhancing clinical exposure, transition to competency-based assessment, and the creation of trainee pathways within 3-year fellowships.

Wolfram syndrome is a rare neurodegenerative disorder, most commonly caused by pathogenic variants in WFS1 , while cases due to CISD2 are exceedingly rare. The estimated prevalence is 1 in 160,000 to 770,000 individuals worldwide. In these clinical guidelines, disorders caused by WFS1 are referred to as WFS1 -Wolfram syndrome, and those caused by CISD2 as CISD2 -Wolfram syndrome. Historically, it has been characterized by early-onset, antibody-negative, insulin-dependent diabetes mellitus, progressive optic atrophy, sensorineural hearing loss, arginine vasopressin deficiency, and brainstem and cerebellar atrophy. More recently, partial and late onset forms have been identified. There are currently no licensed disease-modifying treatments, and international clinical guidelines have not previously been established. An international steering committee systematically reviewed 273 peer-reviewed publications and generated draft consensus statements across six clinical domains. These statements were evaluated by international specialists in endocrinology, clinical genetics, neurology, ophthalmology and neuro-ophthalmology, psychiatry, and urology, drawn from North America, Europe, Latin America, Oceania, and Asia, using a modified three-round Delphi process. Additional feedback was incorporated from nurses specializing in multidisciplinary Wolfram syndrome care, from leaders of international patient organizations, and from specialists in the genetic diagnosis of monogenic diabetes. Structured feedback from patients and families was gathered through multiple international patient advocacy organizations. Consensus was defined as ≥80% agreement. All 35 final consensus statements reached the pre-specified consensus threshold of ≥80% agreement, spanning diagnosis and genetic testing, multidisciplinary care organization, neuro-ophthalmology, neurology, endocrinology, urology, gastroenterology, and psychiatry. These guidelines are the first international clinical consensus for Wolfram syndrome and provide actionable recommendations for clinicians worldwide. Implementation should be accompanied by a prospective audit to expand the evidence base and support future iterations.