Using brief reflections to capture and evaluate end-user engagement: a case example using the COMPASS study.

BACKGROUND: Use of participatory research methods is increasing in research trials. Once partnerships are established with end-users, there is less guidance about processes research teams can use to successfully incorporate end-user feedback. The current study describes the use of a brief reflections process to systematically examine and evaluate the impact of end-user feedback on study conduct. METHODS: The Comparative Effectiveness of Trauma-Focused and Non-Trauma- Focused Treatment Strategies for PTSD among those with Co-Occurring SUD (COMPASS) study was a randomized controlled trial to determine the effectiveness of trauma-focused psychotherapy versus non-trauma-focused psychotherapy for Veterans with co-occurring posttraumatic stress disorder and substance use disorder who were entering substance use treatment within the Department of Veterans Affairs. We developed and paired a process of "brief reflections" with our end-user engagement methods as part of a supplemental evaluation of the COMPASS study engagement plan. Brief reflections were 30-minute semi-structured discussions with the COMPASS Team following meetings with three study engagement panels about feedback received regarding study issues. To evaluate the impact of panel feedback, 16 reflections were audio-recorded, transcribed, rapidly analyzed, and integrated with other study data sources. RESULTS: Brief reflections revealed that the engagement panels made recommended changes in eight areas: enhancing recruitment; study assessment completion; creating uniformity across Study Coordinators; building Study Coordinator connection to Veteran participants; mismatch between study procedures and clinical practice; therapist skill with patients with active substance use; therapist burnout; and dissemination of study findings. Some recommendations positively impact study conduct while others had mixed impact. Reflections were iterative and led to emergent processes that included revisiting previously discussed topics, cross-pollination of ideas across panels, and sparking solutions amongst the Team when the panels did not make any recommendations or recommendations were not feasible. CONCLUSIONS: When paired with end-user engagement methods, brief reflections can facilitate systematic examination of end-user input, particularly when the engagement strategy is robust. Reflections offer a forum of accountability for researchers to give careful thought to end-user recommendations and make timely improvements to the study conduct. Reflections can also facilitate evaluation of these recommendations and reveal end-user-driven strategies that can effectively improve study conduct. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04581434) on October 9, 2020; https://clinicaltrials.gov/ct2/show/study/NCT04581434?term=NCT04581434&draw=2&rank=1 .

Selective adsorption of fluorinated super greenhouse gases within a metal-organic framework with dynamic corrugated ultramicropores.

Perfluorocompound (PFC) gases play vital roles in microelectronics processing. Requirements for ultra-high purities traditionally necessitate use of virgin sources and thereby hinder the capture, purification, and reuse of these costly gases. Most importantly, gaseous PFCs are incredibly potent greenhouse gases with atmospheric lifetimes on the order of 103-104 years, and thus any environmental emissions have an outsized and prolonged impact on our climate. The development of sorbents that can capture PFC gases from industrial waste streams has lagged substantially behind the progress made over the last decade in capturing CO2 from both point emission sources and directly from air. Herein, we show that the metal-organic framework Zn(fba) (fba2- = 4,4'-(hexafluoroisopropylidene)bis-benzoate) displays an equilibrium selectivity for CF4 adsorption over N2 that surpasses those of all water-stable sorbents that have been reported for this separation. Selective adsorption of both CHF3 and CH4 over N2 is also evident, demonstrating a general preference for tetrahedral C1 gases. This selectivity is enabled by adsorption within narrow corrugated channels lined with ligand-based aryl rings, a site within this material that has not previously been realized as being accessible to guests. Analyses of adsorption kinetics and X-ray diffraction data are used to characterize sorption and diffusion of small adsorbates within these channels and strongly implicate rotation of the linker aryl rings as a gate that modulates transport of the C1 gases through a crystallite. Multi-component breakthrough measurements demonstrate that Zn(fba) is able to resolve mixtures of CF4 and N2 under flow-through conditions. Taken together, this work illuminates the dynamic structure of Zn(fba), and also points toward general design principles that can enable large CF4 selectivities in sorbents with more favorable kinetic profiles.

Cholesterol Interference in the Assessment of Vitamin D Status: A Canadian Health Measures Survey Biobank Project.

BACKGROUND: Matrix effects are a known problem with immunoassays measuring serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVES: To determine if the inverse association between serum 25(OH)D and serum cholesterol concentrations is a function of assay method: Diasorin Liaison 25(OH) Vitamin D Total Assay (Liaison Total Assay), an immunoassay, compared with liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: Canadian Health Measures Survey data and biobank serum (White males aged 20-79 y, n = 392) were evaluated for bias in serum 25(OH)D using Bland-Altman plots. Differences in serum 25(OH)D (Liaison Total Assay - LC-MS/MS) were compared among non-HDL-cholesterol <4.2 (n = 295) compared with ≥4.2 (n = 97) mmol/L and total cholesterol groups <5.2 (n = 256) compared with ≥5.2 (n = 136) mmol/L, and associations tested between 25(OH)D and non-HDL-cholesterol or total cholesterol concentrations, using regression. RESULTS: Serum 25(OH)D measured using Liaison Total Assay ranged from 10.7 to 137.0 nmol/L and 14.4 to 137.9 nmol/L by LC-MS/MS. Liaison Total Assay - LC-MS/MS showed a negative bias of 5.5 (95% limits of agreement -23.8, 12.7) nmol/L. Differences in 25(OH)D were -4.0 ± 9.0 (±SD) nmol/L if non-HDL-cholesterol was <4.2 mmol/L and -10.2 ± 8.7 nmol/L if ≥4.2 mmol/L (P < 0.0001). Differences in 25(OH)D, if total cholesterol was <5.2 mmol/L, were -3.4 ± 8.6 nmol/L and -9.6 ± 9.3 nmol/L if ≥5.2 mmol/L (P < 0.0001). Serum non-HDL-cholesterol (beta -3.17, P = 0.0014) and total cholesterol (beta -2.77, P = 0.0046) were inversely associated with Liaison Total Assay 25(OH)D (adjusted for age, fasting, and body mass index), but not with LC-MS/MS measured 25(OH)D. Interference by these lipoproteins was not eliminated by standardization of the Liaison Total Assay. Similar associations were observed with triglycerides as for the lipoproteins. CONCLUSIONS: Total cholesterol inversely associates with 25(OH)D, which is likely due to elevated non-HDL-cholesterol lipoprotein or triglyceride interference with the Liaison Total Assay. This is important as elevated cholesterol is common, and an underestimation of vitamin D status could be an unnecessary cause for concern.

Critical Gaps in Assisted Outpatient Treatment Research in the United States.

In 2023, the White House included the implementation and improvement of assisted outpatient treatment in a list of under-researched strategies to support recovery and long-term treatment engagement for people with serious mental illness. Assisted outpatient treatment is a community-based, court-ordered, mental health treatment program for a subset of individuals with serious mental illness who have a history of difficulty adhering to treatment and staying well while living in the community. There is research supporting the use of assisted outpatient treatment for this specific population, however, the majority focuses on limited geographic regions, specific program organizations, and is outdated. Meanwhile, assisted outpatient treatment programs have increasingly been adopted by counties and states across the country. More research is needed to ensure that assisted outpatient treatment programs are being implemented in the most effective and equitable way possible. In this paper, the authors identify several key gaps in the current literature base relating to the effectiveness and implementation of assisted outpatient treatment.

Adherence to Vitamin D Supplementation Recommendations for Breastfed Infants and Young Children: An Analysis of Canadian Community Health Survey Data Cycles From 2015 to 2018.

BACKGROUND: In Canada, nutrition policy, as outlined in the Nutrition for Healthy Term Infants recommendations, includes a daily vitamin D supplement of 10 µg (400 IU) for breastfed infants and young children to support adequate vitamin D status. OBJECTIVES: This study aimed to report on adherence to vitamin D supplementation recommendations for breastfed infants (≤12 months); and for children breastfed >12 mo. METHODS: Canadian Community Health Survey (paired-cycles 2015/2016 and 2017/2018) maternal experiences data for infants born 2012-2018 who received any breastmilk formed the sample (n = 7079). Whether the infant was given a vitamin D supplement (yes/no) and the frequency (daily/almost every day, 1-2/wk, or <1/wk) were surveyed. Weighted data (95% CI) were summarized according to breastfeeding history (exclusive to 6 mo and continuing; partial to 6 mo and continuing; and stopped ≤6 mo). Correlates of supplement adherence were explored using logistic regression. RESULTS: Overall, 87.1% (95% CI: 85.9%, 88.3%) of participants reported giving their infant (≤12 mo) a vitamin D supplement, and of these, 83.3% (95% CI: 81.9%, 84.7%) did so daily/almost every day, 12.4% (95% CI: 11.1%, 13.7%) did so 1-2/wk, and 4.3% (95% CI: 3.6%, 5.0%) did so <1/wk. Lower adjusted odds of adherence were observed among participants reporting: stopped breastfeeding ≤6 mo, lower education or income, recent immigration, and overweight prepregnancy body mass index; higher odds of adherence were observed in the western provinces. Regarding mothers of children >12 mo and breastfed (n = 2312), 58.0% (95% CI: 54.9%, 61.1%) gave a vitamin D supplement daily/almost every day. CONCLUSIONS: Adherence to providing a vitamin D supplement to breastfed infants is high in Canada. Nonetheless, we estimate that ∼27% of mothers are nonadherent to daily/almost every day administration of a vitamin D supplement and that adherence declines in children breastfed >12 mo. Further promotion to support uptake of the current guidance may be necessary, particularly for parents of recent immigration or lower socioeconomic status.

Investigation of the prevalence and factors influencing tobacco and alcohol use among adolescents in Nigeria: A systematic literature review.

The increase in tobacco and alcohol prevalence among Nigerian teenagers necessitates the need to understand the factors influencing use. The aim of this systematic literature review was to synthesis evidence from studies on tobacco and alcohol use among Nigerian adolescents and young adults in order to determine factors influencing tobacco and alcohol use. Six databases MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ScienceDirect, and Google Scholar were used to search for peer-reviewed articles reporting the prevalence and predictors of tobacco and alcohol use among adolescents/youths published between 2010 and 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guided this review. From our search, twelve articles from the 6 geopolitical zones within Nigeria were included. The high prevalence of tobacco and alcohol use among Nigerian adolescents necessitates the need to understand the factors influencing use. A high prevalence rate was recorded among the male gender. Gender, age, and curiosity appear to place adolescents at extra risk for tobacco and alcohol use. Lack of parental monitoring, peer influence, low socio-economic status, low education level, stressful life events, advertisements, availability, and accessibility are factors identified to influence adolescents' alcohol and tobacco use. Alcohol and tobacco use remains a major public health issue as it continues to contribute largely to the growing occurence of diseases globally. Our review showed that adolescents' alcohol and tobacco use behaviour is triggered by various factors on the personal, interpersonal, organisational, community, and policy levels, and these factors are understood to predict or protect against alcohol and tobacco use.

The cyclimids: Degron-inspired cereblon binders for targeted protein degradation.

Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of ligands that engage CRBN.

WindCline: Sloping wind tunnel for characterizing flame behavior under variable inclines and wind conditions.

Developing accurate computational models of wildfire dynamics is increasingly important due to the substantial and expanding negative impacts of wildfire events on human health, infrastructure, and the environment. Wildfire spread and emissions depend on a number of factors, including fuel type, environmental conditions (moisture, wind speed, etc.), and terrain/location. However, there currently exist only a few experimental facilities that enable testing of the interplay of these factors at length scales <1 m with carefully controlled and characterized boundary conditions and advanced diagnostics. Experiments performed at such facilities are required for informing and validating computational models. Here, we present the design and characterization of a tilting wind tunnel (the "WindCline") for studying wildfire dynamics. The WindCline is unique in that the entire tunnel platform is constructed to pivot around a central axis, which enables the sloping of the entire system without compromising the quality of the flow properties. In addition, this facility has a configurable design for the test section and diffuser to accommodate a suite of advanced diagnostics to aid in the characterization of (1) the parameters needed to establish boundary conditions and (2) flame properties and dynamics. The WindCline thus allows for the measurement and control of several critical wildfire variables and boundary conditions, especially at the small length scales important to the development of high-fidelity computational simulations (10-100 cm). Computational modeling frameworks developed and validated under these controlled conditions can expand understanding of fundamental combustion processes, promoting greater confidence when leveraging these processes in complex combustion environments.

Sequencing and characterizing short tandem repeats in the human genome.

Short tandem repeats (STRs) are highly polymorphic sequences throughout the human genome that are composed of repeated copies of a 1-6-bp motif. Over 1 million variable STR loci are known, some of which regulate gene expression and influence complex traits, such as height. Moreover, variants in at least 60 STR loci cause genetic disorders, including Huntington disease and fragile X syndrome. Accurately identifying and genotyping STR variants is challenging, in particular mapping short reads to repetitive regions and inferring expanded repeat lengths. Recent advances in sequencing technology and computational tools for STR genotyping from sequencing data promise to help overcome this challenge and solve genetically unresolved cases and the 'missing heritability' of polygenic traits. Here, we compare STR genotyping methods, analytical tools and their applications to understand the effect of STR variation on health and disease. We identify emergent opportunities to refine genotyping and quality-control approaches as well as to integrate STRs into variant-calling workflows and large cohort analyses.

Contrast Enhanced CT Radiogenomics in a Retrospective NSCLC Cohort: Models, Attempted Validation of a Published Model and the Relevance of the Clinical Context.

RATIONALE AND OBJECTIVE: To develop a radiogenomic predictive model for non-small cell lung cancer (NSCLC) patients studied through contrast enhanced chest computed tomography (CE-CT) targeting the most frequent gene alterations. M&M: A retrospective study of patients with NSCLC imaged with CE-CT before treatment and had their tumor genomics sequenced at our institution was performed. Data was gathered from their imaging studies, their electronic medical records and a web-based database search (cBioPortal.ca). All of the patient data was tabulated for analysis. Two predictive models (M1 & M2) were created using different approaches and a third model was extracted from the literature to also be tested in our population. RESULTS: Out of 157 patients, eighty were male (51%) and 124 (79%) had a history of smoking. The three most prevalent genes were KRAS, TP53 and EGFR. The M1 radiomics-only model median AUC were 0.61 (TP53), 0.53 (KRAS) and 0.64 (EGFR) and for M1 radiomics + clinical were 0.61 (TP53), 0.61 (KRAS) and 0.80 (EGFR). The M2 radiomics-only model median AUC were 0.63 (TP53), 0.60 (KRAS) and 0.65 (EGFR) and for M2 radiomics + clinical were 0.64 (TP53), 0.62 (KRAS) and 0.81 (EGFR). The external EGFR radiomic model showed an AUC of 0.69 and 0.86 for the radiomics-only and combined radiomics + clinical respectively. CONCLUSION: Our study was able to provide robust predictive radiomics model evaluation for the detection of TP53, KRAS and EGFR. We also compared our performance with an already published model and observed how impactful clinical variables can be on models' performance. CLINICAL RELEVANCE STATEMENT: Identifying tumor mutations in patients that can't undergo biopsy is critical for their outcomes. KEYPOINTS: • Tumor genomic profiling is critical for treatment selection • CE-CT radiomics produce robust predictive models comparable to those already published • Clinical variables should be considered/included in predictive models.

Implementation of a novel peer review academy by Surgery and the Association of Women Surgeons.

BACKGROUND: A novel Peer Review Academy was developed as a collaborative effort between the Association of Women Surgeons and the journal Surgery to provide formal training in peer review. We aimed to describe the outcomes of this initiative using a mixed methods approach. METHODS: We developed a year-long curriculum with monthly online didactic sessions. Women surgical trainee mentees were paired 1:1 with rotating women surgical faculty mentors for 3 formal peer review opportunities. We analyzed pre-course and post-course surveys to evaluate mentee perceptions of the academy and assessed changes in mentee review quality over time with blinded scoring of unedited reviews. Semi-structured interviews were conducted upon course completion. RESULTS: Ten women surgical faculty mentors and 10 women surgical trainees from across the United States and Canada successfully completed the Peer Review Academy. There were improvements in the mentees' confidence for all domains of peer review evaluated, including overall confidence in peer review, study novelty, study design, analytic approach, and review formatting (all, P ≤ .02). The mean score of peer review quality increased over time (59.2 ± 10.8 vs 76.5 ± 9.4; P = .02). In semi-structured interviews, important elements were emphasized across the Innovation, Implementation Process, and Individuals Domains, including the values of (1) a comprehensive approach to formal peer review education; (2) mentoring relationships between women faculty and resident surgeons; and (3) increasing diversity in the scientific peer review process. CONCLUSION: Our novel Peer Review Academy was feasible on a national scale, resulting in significant qualitative and quantitative improvements in women surgical trainee skillsets, and has the potential to grow and diversify the existing peer review pool.

Atlas of nascent RNA transcripts reveals enhancer to gene linkages.

Gene transcription is controlled and modulated by regulatory regions, including enhancers and promoters. These regions are abundant in unstable, non-coding bidirectional transcription. Using nascent RNA transcription data across hundreds of human samples, we identified over 800,000 regions containing bidirectional transcription. We then identify highly correlated transcription between bidirectional and gene regions. The identified correlated pairs, a bidirectional region and a gene, are enriched for disease associated SNPs and often supported by independent 3D data. We present these resources as an SQL database which serves as a resource for future studies into gene regulation, enhancer associated RNAs, and transcription factors.

Ewing's Sarcoma of the Hand: An Unusual Presentation in a Young Hispanic Male.

Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and economic influences including limited English proficiency and insurance status also critically affect the timing of presentation.

Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations.

Background: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR). Methods: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria. Results: In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001). Conclusion: Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

OBJECTIVE: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. METHODS: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. RESULTS: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. INTERPRETATION: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Spondyloarthritides.

The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.

Outcomes after thymectomy in non-thymomatous myasthenia gravis.

Background: Guidelines by the myasthenia gravis (MG) Foundation of America suggest patients aged 18 to 50 years with non-thymomatous myasthenia gravis (NTMG) benefit from thymectomy. Our objective was to investigate utilization of thymectomy in NTMG patients outside the confines of a clinical trial. Methods: From the Optum de-identified Clinformatics Data Mart Claims Database (2007 to 2021), we identified patients diagnosed with MG between 18-50 years old. We then selected patients who received a thymectomy within 12 months of MG diagnosis. Outcomes included use of steroids, non-steroidal immunosuppressive agents (NSIS), and rescue therapy (plasmapheresis or intravenous immunoglobulin), as well as NTMG-related emergency department (ED) visits and hospital admissions. These outcomes were compared in the 6-months before and after thymectomy. Results: A total of 1,298 patients met our inclusion criteria, of whom 45 (3.47%) received a thymectomy, performed via minimally invasive surgery in 53.3% of cases (n=24). In comparing the pre- to post-operative period, we noted that steroid use increased (53.33% to 66.67%, P=0.034), NSIS use remained stable, and use of rescue therapy decreased (44.44% to 24.44%, P=0.007). Costs associated with steroid and NSIS use remained stable. However, the mean costs of rescue therapy decreased (from $13,243.98 to $8,486.26, P=0.035). Hospital admissions and ED visits related to NTMG remained stable. There were 2 readmissions within 90 days (4.44%) associated with thymectomy. Conclusions: Patients with NTMG undergoing thymectomy experienced less need for rescue therapy following resection, albeit with increased rates of steroid prescriptions. Thymectomy is infrequently performed in this patient population despite acceptable postsurgical outcomes.

Parathyroid hormone-vitamin D dynamics vary according to the definition of vitamin D deficiency in newborn infants.

BACKGROUND: Parathyroid hormone (PTH) is an indirect functional indicator of vitamin D status. Risk of vitamin D deficiency, assessed using circulating 25-hydroxyvitamin D (25(OH)D), is defined as <30 nmol/L by the National Academy of Medicine and alternatively <25 nmol/L in the global consensus recommendation on prevention and management of nutritional rickets. OBJECTIVE: To test PTH concentrations and the odds for elevated values according to vitamin D deficiency cut-points (<30 nmol/L, or <25 nmol/L) in newborn infants. METHODS: Healthy term-born infants (n = 858) were recruited from Montreal, Canada (2016-2019). Obstetric data were obtained from medical records, and demographic factors surveyed. Immunoassays were used to measure newborn (24-36 h) serum PTH and 25(OH)D; 25(OH)D was standardized to National Institute of Standards and Technology (NIST) standard reference materials. Serum PTH was log-transformed before comparing serum 25(OH)D groups (<30 vs. ≥30; or <25 vs. ≥25 nmol/L) using ANCOVA adjusted for infant sex, type of delivery, parity, race, and family income. The odds of elevated PTH (>71.48 pg/mL) were tested using logistic regression, adjusted for the same covariates. RESULTS: Infants (50.2 % female) were 39.6 ± 1.0 weeks gestational age (mean ± SD), and 3.41 ± 0.38 kg. Median serum 25(OH)D was 45.4 (IQR 23.2) nmol/L; 20.5 % had serum 25(OH)D < 30 nmol/L, and 12.4 % <25 nmol/L. Median serum PTH was 30.72 (IQR 33.90) pg/mL, elevated in 12.7 % overall, and higher in infants born with serum 25(OH)D < 25 vs. ≥25 nmol/L (35.96 (IQR 39.20) vs. 30.36 (IQR 32.93) pg/mL, p = 0.0158). The odds of elevated PTH were higher when serum 25(OH)D was <25 nmol/L (ORadj 2.13, 95 % CI: 1.23, 3.69). PTH concentration and the odds of being elevated did not differ according to the 30 nmol/L cut-point. CONCLUSIONS: Based on this study, the definition of vitamin D deficiency relative to bone health as set by the National Academy of Medicine (<30 nmol/L) exceeds the threshold at which PTH is elevated in newborn infants.