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The possible mechanisms of action of bovine pancreatic ribonuclease are discussed in the light of the detailed knowledge of the geometry of the active site that has been derived from studies of inhibitor binding by X-ray diffraction and nuclear magnetic resonance. When combined with a knowledge of the mechanism of phosphate ester hydrolysis, this information imposes severe geometric constraints on possible mechanisms of action of the enzyme. Two types of mechanism can be distinguished, the linear and the pseudorotation. The linear mechanism includes a catalytic role for both histidine residues at the active site and does not involve pseudorotation of the intermediate. In contrast, in the pseudorotation mechanism one histidine residue performs all the catalytic functions, while the other serves only to bind the phosphate anion; this necessarily involves pseudorotation of the intermediate and specific protonation of the leaving group by the enzyme. The mode of binding of the product of the reaction, cytidine-3'-monophosphate, has been elucidated by X-ray diffraction and nuclear magnetic resonance. If the substrate binds in an analogous way, only the linear mechanism is possible. This mechanism is described in detail.

The incidence of adoption disruptions is much higher in special-needs adoptions than in infant adoptions. This article reports the results of an analysis of differences in functioning between families able to sustain special-needs placements and families in which they disrupted. The finding is that the father plays a pivotal role in maintaining these placements. If he is actively involved in parenting, and able to nurture and support the mother in her role, placements are more likely to be sustained. [ABSTRACT FROM AUTHOR]

Genetic testing of patients with neurodevelopmental disabilities (NDDs) is critical for diagnosis, medical management, and access to precision therapies. Because genetic testing approaches evolve rapidly, professional society practice guidelines serve an essential role in guiding clinical care; however, several challenges exist regarding the creation and equitable implementation of these guidelines. In this scoping review, we assessed the current state of United States professional societies' guidelines pertaining to genetic testing for unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. We describe several identified shortcomings and argue the need for a unified, frequently updated, and easily-accessible cross-specialty society guideline. ANN NEUROL 2024;96:900-913., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The vacuolar H + -ATPase (V-ATPase) is a functionally conserved multimeric complex localized at the membranes of many organelles where its proton-pumping action is required for proper lumen acidification. The V-ATPase complex is composed of several subunits, some of which have been linked to human disease. We and others previously reported pathogenic dominantly acting variants in ATP6V1B2, the gene encoding the V1B2 subunit, as underlying a clinically variable phenotypic spectrum including dominant deafness-onychodystrophy (DDOD) syndrome, Zimmermann-Laband syndrome (ZLS), and deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures (DOORS) syndrome. Here, we report on an individual with features fitting DOORS syndrome caused by dysregulated ATP6V1C1 function, expand the clinical features associated with ATP6V1B2 pathogenic variants, and provide evidence that these ATP6V1C1/ATP6V1B2 amino acid substitutions result in a gain-of-function mechanism upregulating V-ATPase function that drives increased lysosomal acidification. We demonstrate a disruptive effect of these ATP6V1B2/ATP6V1C1 variants on lysosomal morphology, localization, and function, resulting in a defective autophagic flux and accumulation of lysosomal substrates. We also show that the upregulated V-ATPase function affects cilium biogenesis, further documenting pleiotropy. This work identifies ATP6V1C1 as a new gene associated with a neurodevelopmental phenotype resembling DOORS syndrome, documents the occurrence of a phenotypic continuum between ZLS, and DDOD and DOORS syndromes, and classify these conditions as lysosomal disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Suicide is a leading cause of death among youth in the United States. Pediatric emergency department visits for non-psychiatric concerns present an opportunity to identify youth at risk for suicidality. This quality improvement initiative was undertaken to ensure that those patients identified as low risk for suicide receive resources, bridging the gap between identifying at-risk youth and providing them with appropriate follow up mental health resources. The aim of this project was to increase the proportion of after visit summaries containing mental health resources by 25 % within 6 months for medical patients who are found to have non-acute low suicide risk and are discharged from the emergency department., Methods: The primary outcome measure was the proportion of discharged medical patients who screened positive for suicidal ideation and were determined to be at low risk for suicide who received mental health resources on discharge before and after intervention. A multidisciplinary team targeted the following 3 key drivers: 1) multidisciplinary engagement 2) training and education of providers and 3) health information technology. Plan, Do, Study and Act cycles included the following: 1) an educational campaign with regular multidisciplinary meetings, educational updates, and email reminders; 2). an electronic health record change; and 3) An individual report to providers., Results: After the intervention, the percentage of medical patients with low-risk suicidality being discharged with mental health resources increased by more than 70 %., Conclusions: A champion led multidisciplinary team, using PDSA methodology, can implement sustained improvements in mental health resource distribution., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants., Methods: We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas., Results: All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and "probable EMAtS" in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13)., Significance: POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Due to the multiorgan effects of liver disease, surgical patients with liver disease have an increased risk of perioperative complications. With revision total hip and knee arthroplasty surgeries increasing, it is important to determine the effects of liver disease in this patient population. The purpose of this study was to evaluate the impact of underlying liver disease on postoperative outcomes following revision total joint arthroplasty (TJA)., Methods: The National Surgical Quality Improvement Program database was used to identify patients undergoing aseptic revision TJA from 2006-2019 and group them based on liver disease. The presence of liver disease was assessed by calculating the Model for End-Stage Liver Disease-Sodium score. Patients with a Model for End-Stage Liver Disease-Sodium score of > 10 were classified as having underlying liver disease. In this analysis, differences in demographics, comorbidities, and postoperative complications were assessed., Results: Of 7102 patients undergoing revision total hip arthroplasty, 11.6% of the patients had liver disease. Of 8378 patients undergoing revision total knee arthroplasty, 8.4% of the patients had liver disease. Following adjustment on multivariable regression analysis, patients with liver disease undergoing revision total hip arthroplasty or revision total knee arthroplasty had an increased risk of major complications, wound complications, septic complications, bleeding requiring transfusion, extended length of stay, and readmission compared to those without liver disease., Conclusions: Patients with liver disease have an increased risk of complications following revision TJA. A multidisciplinary team approach should be employed for preoperative optimization and postoperative management of these vulnerable patients to improve outcomes and decrease the incidence and severity of complications., Level of Evidence: This is retrospective cohort study and is level 3 evidence.

Background: Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear., Objectives: Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD., Methods: We studied 102 patients with clinically-defined LBD (Parkinson's disease, n=93; Parkinson's disease dementia, n=4; and dementia with Lewy bodies, n=5) and Epworth Sleepiness Scale (ESS) within 2 years of MRI. Mean diffusivity (MD) was compared between EDS+ (ESS≥10, n=37) and EDS- (ESS<10, n=65) groups in the whole hypothalamus and three subregions, covarying for age and sex. Secondary analyses tested correlations between subregion MD and continuous ESS, global cognition, and motor scores; and between subregion volume and continuous ESS., Results: MD was increased in EDS+ compared to EDS- only in the inferior tuberal subregion (Cohen's d=0.43, p=0.043, β=0.117±0.057), with trend level differences in the whole hypothalamus (Cohen's d=0.39, p=0.064, β=0.070±0.037) and superior tuberal subregion (Cohen's d=0.38, p=0.073, β=0.063±0.035). No difference was seen in the posterior subregion (Cohen's d=0.1, p=0.628, β=0.019±0.038). Significant correlations with continuous ESS were seen in MD of whole hypothalamus (r 2 =0.074, p=0.0057), superior tuberal (r 2 =0.081, p=0.0038), and inferior tuberal (r 2 =0.073, p=0.0059) subregions. There was no correlation of hypothalamic MD with global cognition or motor scores, and no correlation of whole/subregional hypothalamic volumes with ESS., Conclusions: Daytime sleepiness associates with increased MD in the inferior tuberal hypothalamus in an LBD cohort. This suggests degeneration within this region could contribute to EDS symptoms.

Firearm injuries are the leading cause of death among children and adolescents in the US. Safe storage of firearms in the home is one of the most effective ways of preventing firearm injuries in children. This feasibility study was conducted in both the pediatric and general Emergency Departments of a large urban academic medical center in a community with high rates of firearm injuries in children. The objective was to pilot a survey seeking to describe sociodemographic characteristics, firearm specific risk factors, and firearm storage practices of households with children in the community. One hundred participants completed a survey containing items regarding participant demographics, household features, firearm ownership, firearm characteristics, and storage practices. Descriptive statistics were used to define sociodemographic characteristics of the enrolled population, comparing those with firearms to those without, and to describe firearms and storage practices of firearm owners in households with children. Of 100 participants, 30 lived in households with firearms and children. Most firearms in homes with children were stored locked and unloaded most of the time; however, 30% of participants with firearms and children in the home reported not consistently storing a firearm locked and unloaded. The most common reason given for not storing a firearm in the safest manner possible was that storing a firearm locked and unloaded would make it difficult to access quickly. Engaging families with children in discussions around firearm prevention during Emergency Department visits is feasible and may have implications for future efforts to promote safe firearm storage practices., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF., Introduction: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs., Methods: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates., Results: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500., Conclusion: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Introduction: Prior studies have demonstrated HIV does not increase the risk of 2-year complications following TKA; however, the literature is sparse regarding the impact of HIV and AIDS on long-term implant survivorship. The purpose of this study was to compare the 10-year cumulative incidence and risk of revision TKA in patients with and without asymptomatic HIV, and with and without AIDS., Methods: Patients with HIV who underwent elective TKA were identified using a national database and divided into subgroups of asymptomatic HIV (AHIV) and acquired immunodeficiency syndrome (AIDS). These patients with HIV were propensity matched based on age, sex, and Charlson Comorbidity Index (CCI) to a control group of elective TKA patients without HIV in a 1:2 ratio. Patients were also compared to an unmatched control group., Results: The 10-year risk for all-cause revision TKA was higher in the HIV group compared to unmatched controls (HR 1.40, 95% CI 1.02-1.93, p = 0.038) but not matched controls (HR 1.13, 95% CI 0.77-1.63, p = 0.594). When compared to both control groups (unmatched; matched), the AIDS group had a higher risk of 10-year all-cause revision (HR 2.74, 95% CI 1.51-4.99, p < 0.001; HR 2.19, 95% CI 1.17-4.11, p = 0.014), dislocation/instability (HR 4.89, 95% CI 1.54-15.51, p = 0.007; HR 3.86, 95% CI 1.12-13.34, p = 0.033), and periprosthetic fracture [PPF] (HR 0.67, 95% CI 0.16-2.74, p = 0.002; HR 3.82, 95% CI 1.08-13.45, p = 0.037). However, patients with AIDS were not at increased risk of PJI or mechanical loosening compared to unmatched controls or matched controls., Discussion: This study expands on current literature by following a nationwide cohort of HIV/AIDS patients for 10 years after TKA. Although a diagnosis of asymptomatic HIV was not associated with increased risk of 10-year revision rates following TKA, a diagnosis of AIDS was. Surgeons should ensure patients' serum CD4 level is sufficient, ideally in the normal range of 500-1500 cells per mm 3 , before undergoing TKA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Bariatric surgery (BS) is indicated for select class III obesity patients undergoing total knee arthroplasty (TKA) to reduce obesity-related complications. This study assessed the effect of BS on TKA revision rates compared to the general population and class III obesity patients without a history of BS., Methods: A national database identified patients who had primary TKA. They were divided into two groups: those with BS prior to TKA and those without. Patients without BS formed two control groups, a matched general population, and a matched class III obese cohort. The BS group was matched with controls based on age, Charlson Comorbidity Index (CCI), gender, and diabetes mellitus. Revision rates were analyzed using Kaplan-Meier survival analysis and hazard ratios (HR), calculated using Cox proportional hazard modeling., Results: 14,292 BS patients were compared to 57,006 matched general population controls, and 19,504 BS patients were compared to 77,846 matched class III obesity control patients. BS patients had a higher risk of 5-year all-cause revision (HR: 1.13; P = 0.014) and revision due to periprosthetic fracture (HR: 1.39; P < 0.001) compared to the general population. Compared to class III obesity controls, BS patients had a lower risk of 5-year revision due to prosthetic joint infection (HR: 0.77; P = 0.001), with no difference in all-cause revision (P = 0.362)., Conclusion: BS does not reduce all-cause TKA revision risk compared to the general or matched class III obesity population. However, it lowers the risk of revision due to prosthetic joint infection when compared to patients with class III obesity., Level of Evidence: IV., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Savyasachi C Thakkar is an unpaid consultant for KCI and OrthoAlign, editorial/governing board for Arthroplasty Today and Journal of Arthroplasty and Board Member of American Association of Hip and Knee Surgeons. Gregory J Golladay is a recipient of royalties from Stryker and Arthroplasty Today, editorial/governing board for Arthroplasty Today and Journal of Arthroplasty and Board Member of American Association of Hip and Knee Surgeons and Virginia Orthopaedic Society.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is no clear research showcasing bariatric surgery's (BS's) impact on long-term surgical complications following total hip arthroplasty (THA). Therefore, this study compared the 10-year cumulative incidence and risk of revision following THA in patients who underwent BS when compared to the general population and class III obesity patients who did not undergo BS., Methods: Patients who underwent elective THA from 2010 to 2021 were identified using an all-payer claims database. Patients who underwent BS prior to THA were separately matched to a control of the general population and those who had class III obesity (body mass index ≥40) by age, sex, Charlson Comorbidity Index, and diabetes using a 1:4 ratio. Kaplan-Meier analyses generated 10-year cumulative incidence rates, and a Cox proportional hazard ratio (HR) model generated HRs and 95% confidence intervals (CIs)., Results: When compared to the general control, patients who have a history of BS had an elevated 10-year risk of all-cause revision (HR 1.31, 95% CI: 1.16 to 1.47, P < .001), prosthetic joint infection (HR: 1.62, CI: 1.30 to 2.04; P < .001), mechanical loosening (HR: 1.20, CI: 1.01 to 1.44; P = .040), and dislocation/instability (HR: 1.35, CI: 1.09 to 1.68; P = .007). There was no difference in the 10-year risk of all-cause revision or other indications for revision in the BS cohort compared to the matched class III obesity cohort (P = .142)., Conclusions: Those who underwent BS before THA had comparable 10-year revision rates when compared to those who had class III obesity and higher rates compared to the general population. This suggests BS may not reduce the 10-year surgical risks associated with obesity when compared to a class III obese surgical population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bilateral simultaneous total knee arthroplasty (BSTKA) has decreased in frequency due to concerns about higher rates of early mortality and complications than unilateral or staged surgeries. Purpose : We sought to evaluate whether technology assistance (encompassing robotics and computer assistance) decreases early mortality following BSTKA. Methods : We conducted a retrospective cohort study using a national all-payer claims database. Patients who underwent BSTKA from October 2015 to December 2020 were identified. Univariate and multivariable analyses were conducted to compare outcomes in patients who underwent BSTKA with technology assistance compared to conventional instrumentation. The primary outcome was 30-day postoperative mortality. Secondary outcomes were respiratory failure and fat embolism. A post-hoc analysis was performed to evaluate length of stay, readmission, and other medical complications. Results : A total of 14,870 patients who underwent BSTKA were included in this study. Of these, 860 patients underwent technology-assisted BSTKA, and 14,010 patients underwent BSTKA without technology assistance. After a multivariable analysis, patients who underwent technology-assisted BSTKA had equivalent odds of 30-day mortality compared to those who underwent BSTKA without technology assistance. Technology assistance was not protective against the development of acute respiratory failure or fat embolism. Conclusion : This retrospective cohort study found no differences in the rates of 30-day mortality, respiratory failure, or fat embolism after technology-assisted BSTKA compared to conventional BSTKA. On the post-hoc analysis, technology use was associated with a decreased length of stay, lower readmission risk, and decreased rates of deep vein thrombosis, pulmonary embolism, and blood transfusion., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gregory Golladay, MD, reports relationships with Stryker, GLG, Cuerus, Arthroplasty Today, Journal of Arthroplasty, American Association of Hip and Knee Surgeons, and Virginia Orthopaedic Society. Savyasachi Thakkar, MD, reports relationships with KCI, OrthoAlign, Arthroplasty Today, Journal of Arthroplasty, and American Association of Hip and Knee Surgeons. The other authors declare no potential conflicts of interest., (© The Author(s) 2023.)

The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects. We used biochemical assays and confocal microscopy to assess the impact of DENND5B variants on protein accumulation and distribution. Then, exploiting fluorescent lipid cargoes coupled to high-content imaging and analysis in living cells, we investigated whether DENND5B variants affected the dynamics of vesicle-mediated intracellular transport of specific cargoes. We further generated an in silico model to investigate the consequences of DENND5B variants on the DENND5B-RAB39A interaction. Biochemical analysis showed decreased protein levels of DENND5B mutants in various cell types. Functional investigation of DENND5B variants revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. Although none of the variants affected the DENND5B-RAB39A interface, all were predicted to disrupt protein folding. Overall, our findings indicate that DENND5B variants perturb intracellular membrane trafficking pathways and cause a complex neurodevelopmental syndrome with variable epilepsy and white matter involvement., Competing Interests: Declaration of interests A.C. is an employee of GeneDx, LLC. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series., Methods: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant., Results: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing., Interpretation: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population., Methods: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata., Results: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001)., Conclusion: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Triage, the initial assessment and sorting of patients in the Emergency Department (ED), determines priority of evaluation and treatment. Little is known about the impact of undertriage, the underestimation of disease severity at triage, on clinical care in pediatric ED patients. We evaluate the impact of undertriage on time to disposition and treatment decisions in pediatric ED patients., Methods: This was a case control study of ED visits for patients <22 years of age, with an assigned Emergency Severity Index (ESI) score of 4 or 5, and associated hospital admission, nebulized treatment, supplemental oxygen, and/or intravenous (IV) line placement, between January 1, 2018, to June 30, 2022. Controls were sampled from a pool of patient visits with an ESI score of 3, matched by intervention, disposition, and date and hour of arrival. Primary outcome measures were time to order of intervention (nebulized treatment, oxygen administration, or IV placement) and time to disposition decision. A secondary outcome measure was return visits requiring admission or emergency intervention within 14 days of the index visit. Continuous variables (time to orders) were analyzed using Wilcoxon rank sum test and dichotomous outcomes (return visits) were compared using odds ratios with 95% confidence intervals. Analysis was performed with Python v3.10., Results: The final analysis included 7245 undertriaged patients. Undertriaged patients had longer times to orders for nebulized treatments, (p < 0.001) IV placement, (p < 0.001) and admission (p < 0.001) when compared to controls. There were no significant differences in time to supplemental oxygen delivery and time to discharge compared to controls. Undertriaged patients were more likely to experience a return visit requiring admission or emergency intervention (OR 3.74, 95% CI 3.32,4.22)., Conclusions: Undertriage in the pediatric ED is associated with delays in care and disposition decisions and increases likelihood of return visits., Competing Interests: Declaration of Competing Interest DB, JC, NM, CR, JC report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)