Unsupervised Segmentation of Knee Bone Marrow Edema-like Lesions Using Conditional Generative Models.

Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound public health implications. Manual and semi-automatic segmentations of BMELs in magnetic resonance images (MRI) have been used to quantify the significance of BMELs. However, their utilization is hampered by the labor-intensive and time-consuming nature of the process as well as by annotator bias, especially since BMELs exhibit various sizes and irregular shapes with diffuse signal that lead to poor intra- and inter-rater reliability. In this study, we propose a novel unsupervised method for fully automated segmentation of BMELs that leverages conditional diffusion models, multiple MRI sequences that have different contrast of BMELs, and anomaly detection that do not rely on costly and error-prone annotations. We also analyze BMEL segmentation annotations from multiple experts, reporting intra-/inter-rater variability and setting better benchmarks for BMEL segmentation performance.

Hospital costs and reimbursement for short-stay inpatient versus observation status hospitalizations for children with medical complexity.

BACKGROUND: There is a lack of uniformity across hospitals in applying inpatient versus observation status for short-stay (<48 h) pediatric hospitalizations, with negative financial implications associated with observation. Children with medical complexity (CMC) represent a growing population and incur high costs of care. The financial implications of inpatient and observation status for CMC have not been studied. OBJECTIVES: To compare costs and reimbursement for short-stay hospitalizations for CMC by inpatient and observation status, overall and stratified by payor. METHODS: We performed a cohort study of short-stay hospitalizations for CMC from 2016 to 2021 at 10 children's hospitals reporting reimbursement in the Pediatric Health Information System and Revenue Management Program. The primary outcome was the cost coverage ratio (CCR), defined as an encounter's reimbursement divided by the estimated cost. RESULTS: There were 89,282 encounters included. The median costs per encounter were similar across observation ($5206, IQR $3604-$7484) and inpatient ($6547, IQR $4725-$9349) encounters. For government payors, the median CCR was 0.6 (IQR 0.2-0.9) for observation encounters and 1.2 (IQR 0.8-1.9) for inpatient. For nongovernment payors, the median CCR was 1.6 (IQR 1.3-1.9) for observation and 1.6 (IQR 1.4-2) for inpatient. Government reimbursement was associated with increased risk for financial loss (OR 13.91, 95% CI 7.23, 26.77) and with a median net loss of $985,952 (IQR $389,871-$1,700,041) per hospital annually for observation encounters. CONCLUSIONS: Government-paid observation encounters for CMC are associated with significant financial loss at children's hospitals. This reimbursement model may pose a threat to children's hospitals' ability to care for CMC.

Outcomes associated with initial narrow-spectrum versus broad-spectrum antibiotics in children hospitalized with urinary tract infections.

OBJECTIVE: The aim of this study is to describe the proportion of children hospitalized with urinary tract infections (UTIs) who receive initial narrow- versus broad-spectrum antibiotics across children's hospitals and explore whether the use of initial narrow-spectrum antibiotics is associated with different outcomes. DESIGN, SETTING AND PARTICIPANTS: We performed a retrospective cohort analysis of children aged 2 months to 17 years hospitalized with UTI (inclusive of pyelonephritis) using the Pediatric Health Information System (PHIS) database. MAIN OUTCOME AND MEASURES: We analyzed the proportions of children initially receiving narrow- versus broad-spectrum antibiotics; additionally, we compiled antibiogram data for common uropathogenic organisms from participating hospitals to compare with the observed antibiotic susceptibility patterns. We examined the association of antibiotic type with adjusted outcomes including length of stay (LOS), costs, and 7- and 30-day emergency department (ED) revisits and hospital readmissions. RESULTS: We identified 10,740 hospitalizations for UTI across 39 hospitals. Approximately 5% of encounters demonstrated initial narrow-spectrum antibiotics, with hospital-level narrow-spectrum use ranging from <1% to 25%. Approximately 80% of hospital antibiograms demonstrated >80% Escherichia coli susceptibility to cefazolin. In adjusted models, those who received initial narrow-spectrum antibiotics had shorter LOS (narrow-spectrum: 33.1 (95% confidence interval [CI]: 30.8-35.4) h versus broad-spectrum: 46.1 (95% CI: 44.1-48.2) h) and reduced costs [narrow-spectrum: $4570 ($3751-5568) versus broad-spectrum: $5699 ($5005-$6491)]. There were no differences in ED revisits or hospital readmissions. In summary, children's hospitals have low rates of narrow-spectrum antibiotic use for UTIs despite many reporting high rates of cefazolin-susceptible E. coli. These findings, coupled with the observed decreased LOS and costs among those receiving narrow-spectrum antibiotics, highlight potential antibiotic stewardship opportunities.

Lower opportunity ZIP code is associated with worse outcomes after listing in pediatric heart transplantation.

BACKGROUND: The Child Opportunity Index (COI) comprehensively measures children's social determinants of health. We describe association between COI and outcomes after listing for heart transplantation. METHODS: We conducted a retrospective review of the United Network for Organ Sharing (UNOS) database for U.S. children listed for heart transplant between 2012 and 2020. ZIP codes were utilized to assign COI. Primary outcome was survival from time of listing. Secondary outcomes included waitlist survival, 1-year post-transplant survival, and conditional 1-year post-transplant survival. Cox regression was performed adjusting for payor, age, race, diagnosis, and support at listing for all outcomes except waitlist survival, for which Fine-Gray competing risk analysis was performed. RESULTS: Of 5,723 children listed, 109 were excluded due to missing ZIP codes. Race/ethnicity and payor were associated with COI (p < 0.001). Patients living in very low COI ZIP codes compared to all others had increased mortality from time of listing (HR 1.16, CI 1.03-1.32, p = 0.02) with 1-, 5-, and 9-year survival of 79.3% vs 82.2%, 66.5% vs 73.0%, and 53.6% vs 64.7% respectively, were more likely to be removed from the waitlist due to death or being too sick (subdistribution HR 1.26, 95% CI 1.10-1.42), and had increased mortality conditional on one-year post-transplant survival (HR 1.38, 1.09-1.74, p = 0.008) with 1-, 3-, and 5- year survival of 94.7% vs 97.3%, 87.0% vs 93.1%, and 78.6% vs 86.9%. CONCLUSIONS: Children living in lower opportunity ZIP codes had poorer survival from time of listing, poorer waitlist survival, and poorer conditional one-year post-transplant survival.

Pharmacologic Restraint Use During Mental Health Admissions to Children's Hospitals.

OBJECTIVES: Primary mental health admissions are increasing across US children's hospitals. These patients may experience agitation requiring pharmacologic restraint. This study characterized pharmacologic restraint use in medical inpatient units by primary mental health diagnosis. METHODS: This retrospective, cross-sectional study used the Pediatric Health Information System database. The study included children aged 5 to 17 years admitted with a primary mental health diagnosis between 2016 and 2021. Rates of pharmacologic restraint use per 1000 patient days were determined for 13 mental health diagnoses and trended over time with Poisson regression. RESULTS: Of 91 898 hospitalizations across 43 hospitals, 3% of admissions and 1.3% of patient days involved pharmacologic restraint. Trends in the rate of pharmacologic restraint use remained stable (95% confidence interval [CI], 0.7-2.1), whereas the incidence increased by 141%. Diagnoses with the highest rates of pharmacologic restraint days per 1000 patient days included autism (79.4; 95% CI, 56.2-112.3), substance-related disorders (45.0; 95% CI, 35.9-56.4), and disruptive disorders (44.8; 95% CI, 25.1-79.8). The restraint rate significantly increased in disruptive disorders (rate ratio [RR], 1.4; 95% CI, 1.1-1.6), bipolar disorders (RR, 2.0; 95% CI, 1.4-3.0), eating disorders (RR, 2.4; 95% CI, 1.5-3.9), and somatic disorders (RR, 4.2; 95% CI, 1.9-9.1). The rate significantly decreased for autism (RR, 0.8; 95% CI, 0.6-1.0) and anxiety disorders (RR, 0.3; 95% CI, 0.2-0.6). CONCLUSIONS: Pharmacologic restraint use among children hospitalized with a primary mental health diagnosis increased in incidence and varied by diagnosis. Characterizing restraint rates and trends by diagnosis may help identify at-risk patients and guide targeted interventions to improve pharmacologic restraint utilization.

Impact of anakinra use on clinical outcomes in children with moderate or severe multisystem inflammatory syndrome in children: a propensity score matched retrospective cohort study.

BACKGROUND: The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C. METHODS: We included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher's exact tests. RESULTS: Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS. CONCLUSIONS: In patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Cachexia, chorea, and pain in chronic nonbacterial osteitis and inflammatory bowel disease: a case report.

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014). CASE PRESENTATION: A 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease. CONCLUSIONS: Children and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation.

Adding Nocturnal Advanced Practice Providers to an Academic Inpatient Neurology Service Improves Residents' Educational Experience.

Background and Objectives: In the inpatient academic medical center, increased demand for clinical services often equates to an increased workload for trainees, which could have a positive or negative impact on their educational experience. In 2020, our academic medical center hired Advanced Practice Providers (APPs) to provide continuous additional overnight coverage for our neurology ward teaching service. We hypothesized that adding APPs and reducing overnight clinical workload for residents would have a positive impact on resident education. Methods: We performed a mixed-methods, prospective study that included needs-assessments by residents, semi-structured interviews with both residents and APPs, and surveys to residents and nursing staff. In addition, we collected quantitative data such as hours of sleep, number of admissions, and number of pages to capture the impact of APPs on resident overnight shifts. Results: The addition of APPs overnight increased the median hours of sleep overnight from 1 hour to 3 hours (P < .001) and decreased the median number of pages overnight from 31.5 to 17 (P < .001). The median number of patients the resident was responsible for cross-covering overnight decreased from 24 patients to 14 patients (P < .001). The majority of resident responses (94%) agreed that the addition of APPs benefited their education by reducing workload and increasing time allotted to reading and formulating plans for overnight admissions. 88% of residents agreed that the addition of APPs improved quality of life and reduced risk of burnout. Conclusion: Advanced Practice Providers significantly reduced resident workload, leading residents to report improvements in the educational experience overnight and reduced perceived risk of burnout.

National cross-sectional study on cost consciousness, cost accuracy, and national medical waste reduction initiative knowledge among pediatric hospitalists in the United States.

BACKGROUND/OBJECTIVE: Despite initiatives to reduce waste and spending, there is a gap in physician knowledge regarding the cost of commonly ordered items. We examined the relationship between pediatric hospitalists' knowledge of national medical waste reduction initiatives, self-reported level of cost-consciousness (the degree in which cost affects practice), and cost accuracy (how close an estimate is to its hospital cost) at a national level. METHODS: This cross-sectional study used a national, online survey sent to hospitalists at 49 children's hospitals to assess their knowledge of national medical waste reduction initiatives, self-reported cost consciousness, and cost estimates for commonly ordered laboratory studies, medications, and imaging studies. Actual unit costs for each hospital were obtained from the Pediatric Health Information System (PHIS). Cost accuracy was calculated as the percent difference between each respondent's estimate and unit costs, using cost-charge ratios (CCR). RESULTS: The hospitalist response rate was 17.7% (327/1850), representing 40 hospitals. Overall, 33.1% of respondents had no knowledge of national medical waste reduction initiatives and 24.3% had no knowledge of local hospital costs. There was no significant relationship between cost accuracy and knowledge of national medical waste reduction initiatives or high self-reported cost consciousness. Hospitalists with the highest self-reported cost consciousness were the least accurate in estimating costs for commonly ordered laboratory studies, medications, or imaging studies. Respondents overestimated the cost of all items with the largest percent difference with medications. Hospitalists practicing over 15 years had the highest cost accuracy. CONCLUSIONS: A large proportion of pediatric hospitalists lack knowledge on national waste reduction initiatives. Improving the cost-accuracy of pediatric hospitalists may not reduce health care costs as they overestimated many hospital costs. Median unit cost lists could be a resource for educating medical students and residents about health care costs.

Risk of Target Organ Damage in Children With Primary Ambulatory Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. METHODS: A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. RESULTS: Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69-8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m2.7; [95% CI, 3.78-6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20-0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02-0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. CONCLUSIONS: Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020189359.

Trends in Pediatric Rhabdomyolysis and Associated Renal Failure: A 10-Year Population-Based Study.

OBJECTIVES: Rhabdomyolysis in children is a highly variable condition with presentations ranging from myalgias to more severe complications like acute renal failure. We sought to explore demographics and incidence of pediatric rhabdomyolysis hospitalizations and rates of associated renal failure, as our current understanding is limited. METHODS: This was a retrospective analysis using the Healthcare Cost and Utilization Project Kids' Inpatient Database to identify children hospitalized with a primary diagnosis of rhabdomyolysis. Data were analyzed for demographic characteristics, as well as geographic and temporal trends. Multivariable logistic regression was used to identify characteristics associated with rhabdomyolysis-associated acute renal failure. RESULTS: From 2006 to 2016, there were 8599 hospitalized children with a primary diagnosis of rhabdomyolysis. Overall, hospitalizations for pediatric rhabdomyolysis are increasing over time, with geographic peaks in the South and Northeast regions, and seasonal peaks in March and August. Though renal morbidity was diagnosed in 8.5% of children requiring hospitalization for rhabdomyolysis, very few of these patients required renal replacement therapy (0.41%), and death was rare (0.03%). Characteristics associated with renal failure included male sex, age greater than 15 years, and non-Hispanic Black race. CONCLUSIONS: Though renal failure occurs at a significant rate in children hospitalized with rhabdomyolysis, severe complications, including death, are rare. The number of children hospitalized with rhabdomyolysis varies by geographic region and month of the year. Future studies are needed to explore etiologies of rhabdomyolysis and laboratory values that predict higher risk of morbidity and mortality in children with rhabdomyolysis.

Hospital-Level Neighborhood Opportunity and Rehospitalization for Common Diagnoses at US Children's Hospitals.

OBJECTIVE: Neighborhood conditions influence child health outcomes, but data examining association between local factors and hospital utilization are lacking. We determined if hospitals' mix of patients by neighborhood opportunity correlates with rehospitalization for common diagnoses at US children's hospitals. METHODS: We analyzed all discharges in 2018 for children ≤18 years at 47 children's hospitals for 14 common diagnoses. The exposure was hospital-level mean neighborhood opportunity - measured by Child Opportunity Index (COI) - for each diagnosis. The outcome was same-cause rehospitalization within 365 days. We measured association via Pearson correlation coefficient. For diagnoses with significant associations, we also examined shorter rehospitalization time windows and compared unadjusted and COI-adjusted rehospitalization rates. RESULTS: There were 256,871 discharges included. Hospital-level COI ranged from 17th to 70th percentile nationally. Hospitals serving lower COI neighborhoods had more frequent rehospitalization for asthma (ρ -0.34 [95% confidence interval -0.57, -0.06]) and diabetes (ρ -0.33 [-0.56, -0.04]), but fewer primary mental health rehospitalizations (ρ 0.47 [0.21, 0.67]). There was no association for 11 other diagnoses. Secondary timepoint analysis revealed increasing correlation over time, with differences by diagnosis. Adjustment for hospital-level COI resulted in 26%, 32%, and 45% of hospitals changing >1 decile in rehospitalization rank order for diabetes, asthma, and mental health diagnoses, respectively. CONCLUSIONS: Children's hospitals vary widely in their mix of neighborhoods served. Asthma, diabetes, and mental health rehospitalization rates correlate with COI, suggesting that neighborhood factors may influence outcome disparities for these conditions. Hospital outcomes may be affected by neighborhood opportunity, which has implications for benchmarking.

Is there an increased risk for subtrochanteric stress fracture with the Femoral Neck System versus multiple cannulated screws fixation?

Purpose: This study sought to compare the risk of subtrochanteric stress-riser fractures and biomechanical stability of the Femoral Neck System (FNS) versus multiple screw fixation (MSF). Methods: Eight paired cadaveric femurs were randomly assigned to FNS or MSF. Physiologic load mimicking single leg stance at the subtrochanteric region was applied to the constructs. Results: No constructs failed in the subtrochanteric region during loading. There was no significant difference in force (P = 0.364) or loading cycles (P = 0.348) between groups. Conclusion: FNS constructs were not associated with an increased incidence of iatrogenic subtrochanteric fractures or biomechanical stability versus MSF.

Advance Care Planning Preferences in Hong Kong: A Cross-Sectional Study in a Community.

(1) Background: Hong Kong is experiencing population aging, but there is little research on advance care planning. This research asks for community-dwelling older adults' views on advance care planning in order to provide a different angle to the results collected from nursing homes and hospitals. (2) Methods: The targeted respondents were people aged 55 or above. A total of 282 questionnaires were collected using the random sampling method. Respondents were asked whether they would make an advance care plan, whether they would prepare for their death, and whether they had received any death education; they were also given eight statements related to treatments and decision making. (3) Results: The study found that only 17% of the respondents would like to use advance care planning, even after it was explained to them. Advance care planning favorers would be more likely to insist on having wills and would be more likely to trust doctors rather than family members. (4) Conclusions: The results also suggested that the medical care and social support for end-of-life patients should be improved. The results also showed the importance of medical professionals as they showed that respondents wanted advice on end-of-life decision-making from medical professionals.

Chemoprophylaxis for venous thromboembolism in pelvic and/or acetabular fractures: A systematic review.

BACKGROUND: It is unclear which pharmacological agents, and at what dosage and timing, are most effective for venous thromboembolism (VTE) prophylaxis in patients with pelvic/acetabular fractures. METHODS: We searched the Cochrane Database of Systematic Reviews, Embase, Web of Science, EBSCO, and PubMed on October 3, 2020, for English-language studies of VTE prophylaxis in patients with pelvic/acetabular fractures. We applied no date limits. We included studies that compared efficacy of pharmacological agents for VTE prophylaxis, timing of administration of such agents, and/or dosage of such agents. We recorded interventions, sample sizes, and VTE incidence, including deep vein thrombosis (DVT) and pulmonary embolism. RESULTS: Two studies (3604 patients) compared pharmacological agents, reporting that patients who received direct oral anticoagulants (DOACs) were less likely to develop DVT than those who received low molecular weight heparin (LMWH) (p < 0.01). Compared with unfractionated heparin (UH), LMWH was associated with lower odds of VTE (odds ratio [OR] = 0.37, 95% confidence interval [CI]: 0.22-0.63) and death (OR = 0.27, 95% CI: 0.10-0.72). Three studies (3107 patients) compared timing of VTE prophylaxis, reporting that late prophylaxis was associated with higher odds of VTE (OR = 1.9, 95% CI: 1.2-3.2) and death (OR = 4.0, 95% CI: 1.5-11) and higher rates of symptomatic DVT (9.2% vs. 2.5%, p = 0.03; and 22% vs. 3.1%, p = 0.01). One study (31 patients) investigated dosage of VTE prophylaxis, reporting that a higher proportion of patients with acetabular fractures were underdosed (23% of patients below range of anti-Factor Xa [aFXa] had acetabular fractures vs. 4.8% of patients within adequate range of aFXa, p<0.01). CONCLUSIONS: Early VTE chemoprophylaxis (within 24 or 48 h after injury) was better than late administration in terms of VTE and death. Many patients with acetabular fractures are underdosed with LMWH, with inadequate aFXa levels. Compared with UH, LMWH was associated with lower odds of VTE and death. DOACs were associated with lower risk of DVT compared with LMWH. LEVEL OF EVIDENCE: III, systematic review of retrospective cohort studies.

SARM1 knockout does not rescue neuromuscular phenotypes in a Charcot-Marie-Tooth disease Type 1A mouse model.

Charcot-Marie-Tooth disease Type 1A (CMT1A) is caused by duplication of the PMP22 gene and is the most common inherited peripheral neuropathy. Although CMT1A is a dysmyelinating peripheral neuropathy, secondary axon degeneration has been suggested to drive functional deficits in patients. Given that SARM1 knockout is a potent inhibitor of the programmed axon degeneration pathway, we asked whether SARM1 knockout rescues neuromuscular phenotypes in CMT1A model (C3-PMP) mice. CMT1A mice were bred with SARM1 knockout mice to generate CMT1A/SARM1-/- mice. A series of behavioral assays were employed to evaluate motor and sensorimotor function. Electrophysiological and histological studies of the tibial branch of the sciatic nerve were performed. Additionally, gastrocnemius and soleus muscle morphology were evaluated histologically. Although clear behavioral and electrophysiological deficits were observed in CMT1A model mice, genetic deletion of SARM1 conferred no significant improvement. Nerve morphometry revealed predominantly myelin deficits in CMT1A model mice and SARM1 knockout yielded no improvement in all nerve morphometry measures. Similarly, muscle morphometry deficits in CMT1A model mice were not improved by SARM1 knockout. Our findings demonstrate that programmed axon degeneration pathway inhibition does not provide therapeutic benefit in C3-PMP CMT1A model mice. Our results indicate that the clinical phenotypes observed in CMT1A mice are likely caused primarily by prolonged dysmyelination, motivate further investigation into mechanisms of dysmyelination in these mice and necessitate the development of improved CMT1A rodent models that recapitulate the secondary axon degeneration observed in patients.

When discretionary boundary spanning relationships cease becoming discretionary: The impact of closed ties on informal leadership perceptions.

Organizations have recognized that effective informal leadership is a source of competitive advantage and invest heavily in leadership development efforts. Moreover, because of historical shifts in the nature of work, this informal leadership often takes the form of inter-unit boundary spanning. Because of these two developments, discretionary boundary spanning (DBS) between units has increasingly become a critical, dynamic, bottom-up activity where individuals lacking formal authority step up and take on informal leadership responsibilities. In this study, we draw upon Simmelian Tie Theory (STT) to examine the relationship between different types of DBS and formal leaders' perceptions of a subordinate's informal leadership and performance. We empirically document that a small number of closed task-oriented and closed friendship-oriented DBSs are instrumental in helping individuals demonstrate informal leadership. However, we also show that DBS places constraints on informal leadership when closed ties become too numerous. This results in an inverted-U relationship between the number of closed DBS ties and perceptions of leadership where the apex (i.e., point of over-embeddedness) emerges at a smaller number for friendship-oriented DBS relative to the apex for task-oriented DBSs. We discuss the theoretical implications of these results, as well as the practical implications for managers of organizations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Tranexamic acid use in pelvic and/or acetabular fracture surgery: A systematic review and meta-analysis.

PURPOSE: The purpose of this study is to determine whether tranexamic acid (TXA) use was associated with lower rates of blood transfusion in patients undergoing pelvic and/or acetabular fracture surgery. METHODS: Four studies were included, 3 of which were included in the pooled data analysis for a total of 308 patients. RESULTS: The transfusion rate was significantly lower in the TXA group (44%) compared with the non-TXA group (57%) (P = 0.02). CONCLUSION: TXA use was associated with a significantly lower transfusion rate in patients who underwent pelvic and/or acetabular fracture surgery. LEVEL OF EVIDENCE: Level 3. Systematic review of retrospective cohort studies and prospective randomized controlled trials.