CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human ß cell line and human islet ß cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet ß cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39- CAR Tregs had elevated granzyme B expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, ß cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PD-L1/PD-L2 increased ß cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet ß cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction.

Estimating the Impact of Hospital-Level Variation on the Use of Inpatient Rehabilitation Facilities Versus Skilled Nursing Facilities on Individual Patients With Stroke.

BACKGROUND: There is substantial hospital-level variation in the use of Inpatient Rehabilitation Facilities (IRFs) versus Skilled Nursing Facilities (SNFs) among patients with stroke, which is poorly understood. Our objective was to quantify the net effect of the admitting hospital on the probability of receiving IRF or SNF care for individual patients with stroke. METHODS: Using Medicare claims data (2011-2013), a cohort of patients with acute stroke discharged to an IRF or SNF was identified. We generated 2 multivariable logistic regression models. Model 1 predicted IRF admission (versus SNF) using only patient-level factors, whereas model 2 added a hospital random effect term to quantify the hospital effect. The statistical significance and direction of the random effect terms were used to categorize hospitals as being either IRF-favoring, SNF-favoring, or neutral with respect to their discharge patterns. The hospital's impact on individual patient's probability of IRF discharge was estimated by taking the change in individual predicted probabilities (change in individual predicted probability) between the 2 models. Hospital-level effects were categorized as small (<10%), moderate (10%-19%), or large (≥20%) depending on change in individual predicted probability. RESULTS: The cohort included 135 415 patients (average age, 81.5 [SD=8.0] years, 61% female, 91% ischemic stroke) who were discharged from 1816 acute care hospitals to IRFs (n=66 548) or SNFs (n=68 867). Half of hospitals were classified as being either IRF-favoring (n=461, 25.4%) or SNF-favoring (n=485, 26.7%) with the remainder (n=870, 47.9%) considered neutral. Overall, just over half (n=73 428) of patients were treated at hospitals that had moderate or large independent effects on discharge settings. Hospital effects for neutral hospitals were small (ie, change in individual predicted probability <10%) for most patients (72.5%). However, hospital effects were moderate or large for 78.8% and 84.6% of patients treated at IRF- or SNF-favoring hospitals, respectively. CONCLUSIONS: For most patients with stroke, the admitting hospital meaningfully changed the type of rehabilitation care that they received.

Tracheoesophageal fistula due to Candida and Actinomyces co-infection: A case report and comprehensive review of the literature.

Acquired benign tracheoesophageal fistulas and bronchoesophageal fistulas (TEF) are typically associated with granulomatous mediastinal infections, 75% of which are iatrogenic. Candida albicans and Actinomyces are commonly occurring organisms, but are uncommon etiologies of TEF. Normal colonization and the slow growth characteristics of some species of these agents rarely result in infection, mycetoma, and broncholithiasis, and thus, delays in diagnosis and treatment are likely. Few reports describe C. albicans or Actinomyces spp. as the etiology of TEF or broncholithiasis. Herein, we report a case of benign acquired TEF secondary to coinfection of Candida and Actinomyces complicated by the formation of an actinomycetoma and broncholithiasis and a comprehensive literature review to highlight the unique nature of this presentation and offer a diagnostic algorithm for diagnosis and treatment of TEFs. Following a presentation of three months of productive cough, choking sensation, night sweats, and weight loss, a bronchoscopy revealed a fistulous connection between the esophagus and the posterior right middle lobe. Pathology identified a calcified fungus ball and a broncholith secondary to the co-infection of Candida and Actinomyces. This unique presentation of Candida and Actinomyces co-infection and the associated diagnostic algorithm are presented as education and a useful tool for clinicians.

Validation of the PediBIRN-7 clinical prediction rule for pediatric abusive head trauma.

BACKGROUND: The PediBIRN-7 clinical prediction rule incorporates the (positive or negative) predictive contributions of completed abuse evaluations to estimate abusive head trauma (AHT) probability after abuse evaluation. Applying definitional criteria as proxies for AHT and non-AHT ground truth, it performed with sensitivity 0.73 (95 % CI: 0.66-0.79), specificity 0.87 (95 % CI: 0.82-0.90), and ROC-AUC 0.88 (95 % CI: 0.85-0.92) in its derivation study. OBJECTIVE: To validate the PediBIRN-7's AHT prediction performance in a novel, equivalent, patient population. PARTICIPANTS AND SETTINGS: Consecutive, acutely head-injured children <3 years hospitalized for intensive care across eight sites between 2017 and 2020 with completed skeletal surveys and retinal exams (N = 342). METHODS: Secondary analysis of an existing, cross-sectional, prospective dataset, including assignment of patient-specific estimates of AHT probability, calculation of AHT prediction performance measures (ROC-AUC, sensitivity, specificity, predictive values), and completion of sensitivity analyses to estimate best- and worst-case prediction performances. RESULTS: Applying the same definitional criteria, the PediBIRN-7 performed with sensitivity 0.74 (95 % CI: 0.66-0.81), specificity 0.77 (95 % CI: 0.70-0.83), and ROC-AUC 0.83 (95 % CI: 0.78-0.88). The reduction in ROC-AUC was statistically insignificant (p = .07). Applying physicians' final consensus diagnoses as proxies for AHT and non-AHT ground truth, the PediBIRN-7 performed with sensitivity 0.73 (95 % CI: 0.66-0.79), specificity 0.87 (95 % CI: 0.82-0.90), and ROC-AUC 0.90 (95 % CI: 0.87-0.94). Sensitivity analyses demonstrated minimal changes in rule performance. CONCLUSION: The PediBIRN-7's overall AHT prediction performance has been validated in a novel, equivalent, patient population. Its patient-specific estimates of AHT probability can inform physicians' AHT-related diagnostic reasoning after abuse evaluation.

Health Care Disparities in Stroke Rehabilitation.

Stroke outcomes are influenced by factors such as education, lifestyle, and access to care, which determine the extent of functional recovery. Disparities in stroke rehabilitation research have traditionally included age, race/ethnicity, and sex, but other areas make up a gap in the literature. This article conducted a literature review of original research articles published between 2008 and 2022. The article also expands on research that highlights stroke disparities in risk factors, rehabilitative stroke care, language barriers, outcomes for stroke survivors, and interventions focused on rehabilitative stroke disparities.

Racial and Ethnic Disparities in the Medical Management of Poststroke Complications Among Patients With Acute Stroke.

BACKGROUND: To inform clinical practice, we sought to identify racial and ethnic differences in the medical management of common poststroke complications. METHODS AND RESULTS: A cohort of acutely hospitalized, first-time non-Hispanic White (NHW), non-Hispanic Black, and Hispanic patients with stroke was identified from electronic medical records of 51 large health care organizations (January 1, 2003 to December 5, 2022). Matched propensity scores were used to account for baseline differences. Primary outcomes included receipt of medication(s) associated with the management of the following poststroke complications: arousal/fatigue, spasticity, mood, sleep, neurogenic bladder, neurogenic bowel, and seizure. Differences were measured at 14, 90, and 365 days. Subgroup analyses included differences restricted to patients with ischemic stroke, younger age (<65 years), and stratified by decade (2003-2012 and 2013-2022). Before matching, the final cohort consisted of 348 286 patients with first-time stroke. Matching resulted in 63 722 non-Hispanic Black-NHW pairs and 24 009 Hispanic-NHW pairs. Non-Hispanic Black (versus NHW) patients were significantly less likely to be treated for all poststroke complications, with differences largest for arousal/fatigue (relative risk (RR), 0.58 [95% CI, 0.54-0.62]), spasticity (RR, 0.64 [95% CI, 0.0.62-0.67]), and mood disorders (RR, 0.72 [95% CI, 0.70-0.74]) at 14 days. Hispanic-NHW differences were similar, albeit with smaller magnitudes, with the largest differences present for spasticity (RR, 0.67 [95% CI, 0.63-0.72]), arousal/fatigue (RR, 0.77 [95% CI, 0.70-0.85]), and mood disorders (RR, 0.79 [95% CI, 0.77-0.82]). Subgroup analyses revealed similar patterns for ischemic stroke and patients aged <65 years. Disparities for the current decade remained significant but with smaller magnitudes compared with the prior decade. CONCLUSIONS: There are significant racial and ethnic disparities in the treatment of poststroke complications. The differences were greatest at 14 days, outlining the importance of early identification and management.

Retinal hemorrhage variation in inertial versus contact head injuries.

BACKGROUND: Abusive head trauma (AHT) is frequently accompanied by dense/extensive retinal hemorrhages to the periphery with or without retinoschisis (complex retinal hemorrhages, cRH). cRH are uncommon without AHT or major trauma. OBJECTIVE: The study objectives were to determine whether cRH are associated with inertial vs. contact mechanisms and are primary vs. secondary injuries. PARTICIPANTS AND SETTING: This retrospective study utilized a de-identified PediBIRN database of 701 children <3-years-old presenting to intensive care for head trauma. Children with motor vehicle related trauma and preexisting brain abnormalities were excluded. All had imaging showing head injury and a dedicated ophthalmology examination. METHODS: Contact injuries included craniofacial soft tissue injuries, skull fractures and epidural hematoma. Inertial injuries included acute impairment or loss of consciousness and/or bilateral and/or interhemispheric subdural hemorrhage. Abuse was defined in two ways, by 1) predetermined criteria and 2) caretaking physicians/multidisciplinary team's diagnostic consensus. RESULTS: PediBIRN subjects with cRH frequently experienced inertial injury (99.4 % (308/310, OR = 53.74 (16.91-170.77)) but infrequently isolated contact trauma (0.6 % (2/310), OR = 0.02 (0.0004-0.06)). Inertial injuries predominated over contact trauma among children with cRH sorted AHT by predetermined criteria (99.1 % (237/239), OR = 20.20 (6.09-67.01) vs 0.5 % (2/339), OR = 0.04 (0.01-0.17)). Fifty-nine percent of patients with cRH, <24 h altered consciousness, and inertial injuries lacked imaging evidence of brain hypoxia, ischemia, or swelling. CONCLUSIONS: cRH are significantly associated with inertial angular acceleration forces. They can occur without brain hypoxia, ischemia or swelling suggesting they are not secondary injuries.

Refractory Lateral Leg Pain in a 25-Year-Old Competitive Runner: A Report of a Case of Fascial Herniation of the Peroneus Brevis With Complete Resolution After Surgical Decompression.

Fascial herniations of the leg occur when an intracompartmental leg muscle protrudes through weaknesses in the overlying fascial sheath. These fascial defects may be congenital or acquired from trauma involving penetrating injuries to the fascia. Increases in intracompartmental pressure, often resulting from muscular hypertrophy, can lead to muscular herniation through the weakened fascia. This may present as a leg mass which is often misdiagnosed as a hematoma, varicosity, or soft-tissue mass, leading to significant delays in treatment. We present a case of a peroneus brevis herniation in a 25-year-old male competitive runner with a history of a tibial stress fracture. This patient was referred to the senior author following three years of lateral leg pain worsened by activity. After confirmation of the herniation on MRI, the patient underwent a limited lateral compartment fasciotomy with complete resolution of symptoms at a six-month follow-up. This case demonstrates common pitfalls in the diagnosis of fascial herniations in refractory leg pain of runners. A comprehensive knowledge of this diagnosis and its risk factors can aid in the successful treatment of this patient cohort.

Recurrence of low back pain: A difficult outcome to predict. Development and validation of a multivariable prediction model for recurrence in patients recently recovered from an episode of non-specific low back pain.

BACKGROUND: Recurrence of low back pain (LBP) is common. If clinicians could identify an individual's risk of recurrence, this would enhance clinical decision-making and tailored patient care. OBJECTIVE/DESIGN: To develop and validate a simple tool to predict the probability of a recurrence of LBP by 3- or 12-months following recovery. METHODS: Data utilised for the prediction model development came from a prospective inception cohort study of participants (n = 250) recently recovered from LBP, who had sought care from chiropractic or physiotherapy services. The outcome measure was a recurrence of activity-limiting LBP. Candidate predictor variables (e.g., basic demographics, LBP history, levels of physical activity, etc) collected at baseline were considered for inclusion in a multivariable Cox model. The model's performance was tested in a separate validation dataset of participants (n = 261) involved in a randomised controlled trial investigating exercise for the prevention of LBP recurrences. RESULTS: The final model included the number of previous episodes, total sitting time, and level of education. In the development sample, discrimination was acceptable (Harrell's C-statistic = 0.61, 95% CI, 0.59-0.62), but in the validation sample, discrimination was poor (0.56, 95% CI, 0.54-0.58). Calibration of the model in the validation dataset was acceptable at 3 months but was less precise at 12 months. CONCLUSION: The developed prediction model, which included number of previous episodes, total sitting time, and level of education, did not perform adequately in the validation sample to recommend its use in clinical practice. Predicting recurrence of LBP in clinical practice remains challenging.

Skeletal survey yields in low vs. high risk pediatric patients with skull fractures.

BACKGROUND: To assess for occult fractures, physicians often opt to obtain skeletal surveys (SS) in young, acutely head-injured patients who present with skull fractures. Data informing optimal decision management are lacking. OBJECTIVE: To determine the positive yields of radiologic SS in young patients with skull fractures presumed to be at low vs. high risk for abuse. PARTICIPANTS AND SETTING: 476 acutely head injured, skull-fractured patients <3 years hospitalized for intensive care across 18 sites between February 2011 and March 2021. METHODS: We conducted a retrospective, secondary analysis of the combined, prospective Pediatric Brain Injury Research Network (PediBIRN) data set. RESULTS: 204 (43 %) of 476 patients had simple, linear, parietal skull fractures. 272 (57 %) had more complex skull fracture(s). Only 315 (66 %) of 476 patients underwent SS, including 102 (32 %) patients presumed to be at low risk for abuse (patients who presented with a consistent history of accidental trauma; intracranial injuries no deeper than the cortical brain; and no respiratory compromise, alteration or loss of consciousness, seizures, or skin injuries suspicious for abuse). Only one of 102 low risk patients revealed findings indicative of abuse. In two other low risk patients, SS helped to confirm metabolic bone disease. CONCLUSIONS: Less than 1 % of low risk patients under three years of age who presented with simple or complex skull fracture(s) revealed other abusive fractures. Our results could inform efforts to reduce unnecessary skeletal surveys.

Child Abuse Pediatrics Research Network: The CAPNET Core Data Project.

OBJECTIVE: Examine the epidemiology of subspecialty physical abuse evaluations within CAPNET, a multicenter child abuse pediatrics research network. METHODS: We conducted a cross-sectional study of children <10 years old who underwent an evaluation (in-person or remote) by a child abuse pediatrician (CAP) due to concerns for physical abuse at ten CAPNET hospital systems from February 2021 through December 2021. RESULTS: Among 3667 patients with 3721 encounters, 69.4% were <3 years old; 44.3% <1 year old, 59.1% male; 27.1% Black; 57.8% White, 17.0% Hispanic; and 71.0 % had public insurance. The highest level of care was outpatient/emergency department in 60.7%, inpatient unit in 28.0% and intensive care in 11.4%. CAPs performed 79.1% in-person consultations and 20.9% remote consultations. Overall, the most frequent injuries were bruises (35.2%), fractures (29.0%), and traumatic brain injuries (TBI) (16.2%). Abdominal (1.2%) and spine injuries (1.6%) were uncommon. TBI was diagnosed in 30.6% of infants but only 8.4% of 1-year old children. In 68.2% of cases a report to child protective services (CPS) was made prior to CAP consultation; in 12.4% a report was made after CAP consultation. CAPs reported no concern for abuse in 43.0% of cases and mild/intermediate concern in 22.3%. Only 14.2% were categorized as definite abuse. CONCLUSION: Most children in CAPNET were <3 years old with bruises, fractures, or intracranial injuries. CPS reports were frequently made prior to CAP consultation. CAPs had a low level of concern for abuse in majority of cases.

The association of subcortical brain injury and abusive head trauma.

BACKGROUND: Abusive head trauma (AHT) remains a major pediatric problem with diagnostic challenges. A small pilot study previously associated subcortical brain injury with AHT. OBJECTIVES: To investigate the association of subcortical injury on neuroimaging with the diagnosis of AHT. PARTICIPANTS AND SETTING: Children <3 years with acute TBI admitted to 18 PICUs between 2011 and 2021. METHODS: Secondary analysis of existing, combined, de-identified, cross-sectional dataset. RESULTS: Deepest location of visible injury was characterized as scalp/skull/epidural (n = 170), subarachnoid/subdural (n = 386), cortical brain (n = 170), or subcortical brain (n = 247) (total n = 973). Subcortical injury was significantly associated with AHT using both physicians' diagnostic impression (OR: 8.41 [95 % CI: 5.82-12.44]) and a priori definitional criteria (OR: 5.99 [95 % CI: 4.31-8.43]). Caregiver reports consistent with the child's gross motor skills and historically consistent with repetition decreased as deepest location of injury increased, p < 0.001. Patients with subcortical injuries were significantly more likely to have traumatic extracranial injuries such as rib fractures (OR 3.36, 95 % CI 2.30-4.92) or retinal hemorrhages (OR 5.97, 95 % CI 4.35-8.24), respiratory compromise (OR 12.12, 95 % CI 8.49-17.62), circulatory compromise (OR 6.71, 95 % CI 4.87-9.29), seizures (OR 3.18, 95 % CI 2.35-4.29), and acute encephalopathy (OR 12.44, 95 % CI 8.16-19.68). CONCLUSIONS: Subcortical injury is associated with a diagnosis of AHT, historical inaccuracies concerning for abuse, traumatic extracranial injuries, and increased severity of illness including respiratory and circulatory compromise, seizures, and prolonged loss of consciousness. Presence of subcortical injury should be considered as one component of the complex AHT diagnostic process.

The CAPNET multi-center data set for child physical abuse: Rationale, methods and scope.

BACKGROUND: The pediatric subspecialty of Child Abuse Pediatrics (CAP) was certified by the American Board of Medical Subspecialties in 2006. Relative to its impact on pediatric health, CAP-focused research has been relatively under-funded. Multi-center networks related to CAP-focused research have made important advances, but have been limited in scope and duration. CAPNET is multi-center network whose mission is to support CAP-focused research. OBJECTIVE: To describe the rationale, development, and scope of the CAPNET research network infrastructure, the CAPNET data registry and associated data resources. METHODS: Based on existing priorities for CAP-focused research, we used consensus building and iterative testing to establish inclusion criteria, common data elements, data quality assurance, and data sharing processes for children with concerns of physical abuse. RESULTS: We describe the rationale, methods and intended scope for the development of the CAPNET research network and data registry. CAPNET is currently abstracting data for children <10 years (120 months) old who undergo sub-specialty evaluation for physical abuse at 10 US pediatric centers (approximately 4000 evaluations/year total) using an online data capture form. Data domains include: demographics; visit timing and providers, medical/social history, presentation, examination findings, laboratory and radiographic testing, diagnoses, outcomes, and data for contact children. We describe the methods and criteria for collecting and validating data which are broadly available to CAP investigators. CONCLUSIONS: CAPNET represents a new data resource for the CAP research community and will increase the quantity and quality of CAP-focused research.

An analysis of physicians' diagnostic reasoning regarding pediatric abusive head trauma.

BACKGROUND: Physician diagnoses of abusive head trauma (AHT) have been criticized for circular reasoning and over-reliance on a "triad" of findings. Absent a gold standard, analyses that apply restrictive reference standards for AHT and non-AHT could serve to confirm or refute these criticisms. OBJECTIVES: To compare clinical presentations and injuries in patients with witnessed/admitted AHT vs. witnessed non-AHT, and with witnessed/admitted AHT vs. physician diagnosed AHT not witnessed/admitted. To measure the triad's AHT test performance in patients with witnessed/admitted AHT vs. witnessed non-AHT. PARTICIPANTS AND SETTING: Acutely head injured patients <3 years hospitalized for intensive care across 18 sites between 2010 and 2021. METHODS: Secondary analyses of existing, combined, cross-sectional datasets. Probability values and odds ratios were used to identify and characterize differences. Test performance measures included sensitivity, specificity, and predictive values. RESULTS: Compared to patients with witnessed non-AHT (n = 100), patients with witnessed/admitted AHT (n = 58) presented more frequently with respiratory compromise (OR 2.94, 95% CI: 1.50-5.75); prolonged encephalopathy (OR 5.23, 95% CI: 2.51-10.89); torso, ear, or neck bruising (OR 11.87, 95% CI: 4.48-31.48); bilateral subdural hemorrhages (OR 8.21, 95% CI: 3.94-17.13); diffuse brain hypoxia, ischemia, or swelling (OR 6.51, 95% CI: 3.06-13.02); and dense, extensive retinal hemorrhages (OR 7.59, 95% CI: 2.85-20.25). All differences were statistically significant (p ≤ .001). No significant differences were observed in patients with witnessed/admitted AHT (n = 58) vs. patients diagnosed with AHT not witnessed/admitted (n = 438). The triad demonstrated AHT specificity and positive predictive value ≥0.96. CONCLUSIONS: The observed differences in patients with witnessed/admitted AHT vs. witnessed non-AHT substantiate prior reports. The complete absence of differences in patients with witnessed/admitted AHT vs. physician diagnosed AHT not witnessed/admitted supports an impression that physicians apply diagnostic reasoning informed by knowledge of previously reported injury patterns. Concern for abuse is justified in patients who present with "the triad."

Assessment of salivary gland function after 177Lu-PSMA radioligand therapy: Current concepts in imaging and management.

Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (177Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted 177Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of 177Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post 177Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere.

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species-season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds.

Emulating 3 Clinical Trials That Compare Stroke Rehabilitation at Inpatient Rehabilitation Facilities With Skilled Nursing Facilities.

OBJECTIVE: To inform the design of a potential future randomized controlled trial (RCT), we emulated 3 trials where patient-level outcomes were compared after stroke rehabilitation at inpatient rehabilitation facilities (IRFs) with skilled nursing facilities (SNFs). DESIGN: Trials were emulated using a 1:1 matched propensity score analysis. The 3 trials differed because facilities from rehabilitation networks with different case volumes were compared. Rehabilitation network case volumes were based on the number of patients with stroke that each hospital discharged to each specific IRF or SNF. Trial 1 included 60,529 patients from all networks, trial 2 included 34,444 patients from networks with medium and large case volumes (ie, ≥5 patients), and trial 3 included 19,161 patients from networks with large case volumes (ie, ≥10 patients). The E values were calculated to estimate the minimum strength that an unmeasured confounder would need to be to nullify the results. SETTING: A national sample of IRFs and SNFs from across the United States. PARTICIPANTS: Fee-for-service Medicare patients with acute stroke who received IRF or SNF based rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: One-year successful community discharge (home for >30 consecutive days) and all-cause mortality. RESULTS: Overall, 29,500, 15,156, and 7450 patients were matched for trials 1, 2, and 3. For 1-year successful community discharge, absolute risk differences for IRF patients were 0.21 (95% CI, 0.20-0.22), 0.17 (95% CI, 0.16-0.19), and 0.12 (95% CI, 0.10-0.14) in trials 1, 2, and 3, respectively. For 1-year all-cause mortality, corresponding risk differences were -0.11 (95% CI, -0.12 to -0.11), -0.11 (95% CI, -0.12 to -0.09), and -0.08 (95% CI, -0.10 to -0.06). The E values indicated that a moderately sized unmeasured confounder, with a relative risk of 1.6-2.0 would nullify differences in successful community discharge. CONCLUSIONS: IRF patients had superior outcomes, but differences were attenuated when IRFs and SNFs from larger rehabilitation networks were compared. The vulnerability of the findings to unmeasured confounding supports the need for an RCT.

External Validation of the PediBIRN Screening Tool for Abusive Head Trauma in Pediatric Emergency Department Settings.

METHODS: We conducted a retrospective, secondary analysis of an existing, deidentified, prospective data set captured to derive a bruising CDR. Subjects were patients under 3 years with bruising and confirmed acute head trauma. An expert medical panel had previously identified patients with AHT. Measures of the CDR's AHT screening performance (sensitivity, specificity, likelihood ratios) were calculated with 95% confidence intervals (CIs). RESULTS: Expert medical panel members had classified 78 of 117 eligible patients (67%) as AHT, 38 (33%) as non-AHT, and 1 as indeterminate. Excluding the indeterminate case, the PediBIRN-4 demonstrated a sensitivity of 0.96 (95% CI, 0.88-0.99), specificity of 0.29 (95% CI, 0.16-0.46), positive likelihood ratio of 1.35 (95% CI, 1.10-1.67), and negative likelihood ratio of 0.13 (95% CI, 0.04-0.46). Close inspection of the data revealed that 1 of the CDR's predictor variables had lowered specificity without impacting sensitivity. Eliminating this variable would have increased specificity to 0.84 (95% CI, 0.68-0.93). CONCLUSIONS: The PediBIRN 4-variable CDR demonstrated AHT screening sensitivity in the pediatric ED equivalent to pediatric intensive care unit and other inpatient settings, but lower specificity. Further study of a simplified 3-variable PediBIRN AHT screening tool for the ED setting is warranted.