Hospital variation in adoption of balanced transfusion practices among injured patients requiring blood transfusions.

BACKGROUND: This study sought to measure hospital variability in adoption of balanced transfusion following the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) guidelines. We hypothesized hospital adoption rates of balanced transfusion would be low, and vary significantly among hospitals after controlling for patient, injury and hospital characteristics. STUDY DESIGN AND METHODS: This was an observational cohort study of injured adult patients (≥16 years) in Trauma Quality Improvement Program hospitals 2016-2021. Inclusion criteria were hypotensive patients receiving one transfusion of packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate. Balanced transfusion was defined as ≥1 ratio of plasma to packed red blood cells or platelets to packed red blood cells or whole blood use at 4 hours. Hierarchical multivariable logistic regression quantified residual hospital-level variability in balanced transfusion rates after adjusting for patient and hospital characteristics. RESULTS: Among 172,457 injured patients who received transfusions, 30,386 (17.6%) underwent balanced transfusion. Patient-level balanced transfusion rates were 11% in 2016, rose to 14.0% in 2019, and jumped up once whole blood transfusions were measured to 24.0% in 2020 and to 25.9% in 2021. Approximately 26% of the variability in balanced transfusion rates was attributable to the hospital. Verified level I hospitals had a 2.09 increased adjusted odds of balanced transfusion (95% CI 1.88-2.21) compared to nonverified hospitals. University teaching status had a 1.29 increased adjusted odds of balanced transfusion (95% CI 1.08-1.54) compared with community hospitals. Overall, 150 (23.5%) hospitals were high outliers (high performing) in balanced transfusion adoption and 124 (19.4%) hospitals were low outliers. CONCLUSION: There was significant variability in hospital adoption of balanced transfusion.

Functional Analysis and Chained Schedule Treatment of Elopement in Teens with Autism Spectrum Disorder.

Elopement is one of the most common forms of problem behavior for individuals with autism spectrum disorder (ASD) and is associated with the greatest probability of a lethal outcome. This study evaluated the effects of a function-based treatment package on elopement for two teenage boys with ASD who eloped frequently from caregivers. Functional analyses (FA) identified the variables that evoked and maintained each teen's elopement. Treatment involved a chained schedule comprised primarily of empirically derived differential reinforcement of other behavior (DRO), functional communication training (FCT), and extinction procedures. The treatment produced clinically significant decreases in elopement for both teens. Decreases in elopement maintained when the treatment evaluation was extended to additional contexts. The current study extends the literature on assessment and treatment of elopement and chained schedule treatments that involve both DRO and FCT.

Cost Implications of Insurance Associated Disparities in Post-Acute Traumatic Brain and Spinal Cord Injury Rehabilitation.

Abstract Post-acute care after spinal cord injury (SCI) or traumatic brain injury (TBI) influences neurological function regained. Inpatient rehabilitation facilities (IRFs) have more intensive care and result in lower mortality and better functional outcomes compared with skilled nursing facilities (SNFs). This study sought to quantify inpatient rehabilitation access by insurance and estimate the cost implications. We conducted a retrospective observational cohort study utilizing 2015-2017 California Office of Statewide Health Planning and Development database of injured adults with SCI and/or TBI. The primary predictor was insurance status. The outcome was discharge destination (home, IRFs, SNFs, long-term acute care [LTAC]) modeled using multi-variable multinomial mixed-effects logistic regression controlling for age, diagnosis, Weighted Elixhauser Comorbidity Index, and New Injury Severity Score. Cost of care for discharge to IRFs versus SNFs was estimated by adjusted quantile regression. Cost simulation predicted the adjusted cost difference if all publicly insured participants were discharged to an IRF. We identified 83,230 patients with an injury mechanism and a primary acute care hospitalization diagnosis of TBI (90.9%), SCI (8.3%), or both (0.8%) who were discharged to an IRF, SNF, LTAC, or home. Publicly insured patients were more likely than privately insured patients to go to SNFs versus IRFs (odds ratio [OR]: 2.17, 95% confidence interval [CI 2.01-2.34]). Sub-group analysis of 6416 participants showed an adjusted median total cost difference of $18,461 (95% CI [$5,908-$38,064]) and adjusted cost-per-day of the post-acute encounter of $1,045 (95% CI [$752-$2,399]) higher for discharge to IRFs versus SNFs. Cost simulation demonstrated an additional adjusted cost of $364M annually for universal IRF access for the publicly insured. Publicly insured SCI and TBI Californians are less frequently discharged to IRFs compared with their privately insured counterparts resulting in a lower short-term cost of care. However, the consequences of decreased intensive rehabilitation utilization in terms of functional recovery and long-term cost implications require further investigation.

National Comparison of Program Director Perceptions vs. Resident Reports of the Learning Environment and Well-Being.

OBJECTIVE: Our research objectives were to (1) assess the correlation between PD perceptions and their residents' reported experiences and (2) identify PD and program characteristics associated with alignment between PD perceptions and their residents' reports. DESIGN, SETTING, PARTICIPANTS: A survey was administered to US general surgery residents following the 2019 American Board of Surgery In-Training Examination (ABSITE) to study wellness (burnout, thoughts of attrition, and suicidality) and mistreatment (gender discrimination, sexual harassment, racial/ethnic/religious discrimination, bullying). General surgery program directors (PDs) were surveyed about the degree to which they perceived mistreatment and wellness within their programs. Concordance between PDs' perceptions and their residents' reports was assessed using Spearman correlations. Multivariable logistic regression models examined factors associated with alignment between PDs and residents. RESULTS: Of 6,126 residents training at SECOND Trial-enrolled programs, 5,240 (85.5%) responded to the ABSITE survey. All 212 PDs of programs enrolled in the SECOND Trial (100%) responded to the PD survey. Nationally, the proportion of PDs perceiving wellness issues was similar to the proportion of residents reporting them (e.g., 54.9% of PDs perceive that burnout is a problem vs. 40.1% of residents experience at least one burnout symptom weekly); however, the proportion of PDs perceiving mistreatment vastly underestimated the proportion of residents reporting it (e.g., 9.3% of all PDs perceive vs. 65.9% of all residents report bullying). Correlations between PDs' perceptions of problems within their program and their residents' reports were weak for racial/ethnic/religious discrimination (r = 0.176, p = 0.019), sexual harassment (r = 0.180, p = 0.019), burnout (r = 0.198, p = 0.007), and thoughts of attrition (r = 0.193, p = 0.007), and non-existent for gender discrimination, bullying, or suicidality. Multivariable regression models did not identify any program or PD characteristics that were consistently associated with improved resident-program director alignment. CONCLUSIONS: Resident and PD perceptions were generally disparate regarding mistreatment, burnout, thoughts of attrition, and suicidality. Reconciling this discrepancy is critical to enacting meaningful change to improve the learning environment and resident well-being.

Sex-Based Disparities in Timeliness of Trauma Care and Discharge Disposition.

Importance: Differences in time to diagnostic and therapeutic measures can contribute to disparities in outcomes. However, whether there is an association of timeliness by sex for trauma patients is unknown. Objective: To investigate whether sex-based differences in time to definitive interventions exist for trauma patients in the US and whether these differences are associated with outcomes. Design, Setting, and Participants: This was a retrospective cohort study conducted from July 2020 to July 2021, using the 2013 to 2016 Trauma Quality Improvement Program (TQIP) databases from level I to III trauma centers in the US. Patients 18 years or older with an Injury Severity Score (ISS) greater than 15 and who carried diagnoses of traumatic brain injury, intra-abdominal injury, pelvic fracture, femur fracture, and spinal injury as a result of their trauma were included in the study. Data were analyzed from July 2020 to July 2021. Main Outcomes and Measures: Primary outcomes assessed timeliness to interventions, using Wilcoxon signed rank and χ2 tests. Secondary outcomes included location of discharge after injury, using propensity score-matched generalized estimating equations modeling. Results: Of the 28 332 patients included, 20 002 (70.6%) were male patients (mean [SD] age, 43.3 [18.2] years) and 8330 (29.4%) were female patients (mean [SD] age, 48.5 [21.1] years), with significantly different distributions of ISS scores (ISS score 16-24: male patient, 10 622 [53.1%]; female patient, 4684 [56.2%]; ISS score 41-74: male patient, 2052 [10.3%]; female patient, 852 [10.2%]). Male patients more frequently had abdominal (4257 [21.3%] vs 1268 [15.2%]) and spinal cord (3989 [20.0%] vs 1274 [15.3%]) injuries, whereas female patients experienced greater proportions of femur (3670 [44.0%] vs 8422 [42.1%]) and pelvic (3970 [47.6%] vs 6963 [34.8%]) fractures. Female patients experienced significantly longer emergency department length of stay (median [IQR], 184 [92-314] minutes vs 172 [86-289] minutes; P < .001), longer time in pretriage (median [IQR], 52 [36-80] minutes vs 49 [34-77] minutes; P < .001), and increased likelihood of discharge to nursing or long-term care facilities instead of home after matching by age, ISS, mechanism, and injury type (male patient:female patient, odds ratio, 0.72; 95% CI, 0.67-0.78). Conclusions and Relevance: Results of this cohort study suggest that female trauma patients experienced slightly longer delays in trauma care and had a higher likelihood of discharge to long-term care facilities than their male counterparts.

Time to OR for patients with abdominal gunshot wounds: A potential process measure to assess the quality of trauma care?

BACKGROUND: Abdominal gunshot wounds (GSWs) require rapid assessment and operative intervention to reduce the risk of death and complications. We sought to determine if time to the operating room (OR) might be a useful process measure for the assessment of trauma care quality. We evaluated the facility benchmark time to OR for patients with serious injury and whether this was associated with lower rates of complications and mortality. METHODS: We evaluated time to OR for adult patients with an abdominal GSW presenting in shock to American College of Surgeons Trauma Quality Improvement Program centers from 2015 to 2020. We calculated the 75th percentile time to the OR for each center and characterized centers as average, slow, or fast. We compared patient and facility characteristics across outlier status, as well as risk-adjusted complications and mortality using hierarchical multivariable logistic regression models. RESULTS: There were 4,027 patients in 230 centers that met the inclusion criteria. Mortality was 28%. There were 61 (27%) fast and 52 (23%) slow centers. The median time for slow centers was 83 minutes (68-94 minutes) compared with fast centers, 35 minutes (32-38 minutes). Injury Severity Score and emergency department vital signs were similar across centers. Fast hospitals had higher total case volumes, more cases per surgeon, and were more likely to be Level I centers. Patients cared for in these centers had similar risk-adjusted rates of complications and mortality. CONCLUSION: Time to OR for patients with abdominal GSWs and shock might be a useful process measure to evaluate rapid decision making and OR access. Surgeon and center experience as measured by annual case volumes, coupled with a rapid surgical response required through Level I trauma center standards might be contributory. There was no association between outlier status and complications or mortality suggesting other factors apart from time to the OR are of greater significance. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

An intensive telehealth assessment and treatment model for an adult with developmental disabilities.

Over the last decade, the provision of applied behavior analysis (ABA) services within a telehealth delivery format has had a flourishing literature base. Research has demonstrated that caregivers can successfully conduct functional analyses and functional communication training to treat challenging behavior with coaching from practitioners via telehealth. Previous limitations include research that has only been conducted with children, typically in 1hr, weekly meetings, so the utility of providing ABA therapy via telehealth across the lifespan is unknown. Additionally, the effects of a more intensive treatment format delivered via telehealth has not been evaluated. The purpose of the current study was to coach caregivers to conduct the assessment and treatment process for a young man with developmental disabilities using an intensive-outpatient model in a telehealth format. Functional analysis procedures led to the development of a function-based treatment to reduce challenging behavior and increase functional communication. Caregivers demonstrated high procedural integrity across all phases of the study and found the intervention highly acceptable and effective. Areas for future research and directions are discussed.

Sex Differences in Externalizing and Internalizing Symptoms of Children with ASD.

This study examined sex differences in externalizing and internalizing symptoms of children with ASD without intellectual disability (ID). The sample (n = 80) included 40 girls and 40 boys, ages 6-12 years, with ASD (without ID) matched on age and IQ. Externalizing and internalizing symptoms were significantly elevated for this sample (girls and boys) relative to normative estimates for all the scales (hyperactivity, aggression, anxiety, and depression) except conduct problems. No significant differences were found between girls and boys for either externalizing symptoms or internalizing symptoms (based on standard score and raw score analyses). Implications for clinical practice and future research are discussed.

Brief Report: Examination of Sex-Based Differences in ASD Symptom Severity Among High-Functioning Children with ASD Using the SRS-2.

Prior studies of sex-based differences in autism spectrum disorder (ASD) have yielded mixed findings. This study examined ASD symptom severity and functional correlates in a sample of 34 high-functioning females with ASD (HFASD; M age = 8.93; M IQ = 104.64) compared to 34 matched males (M age = 8.96; M IQ = 104.44) using the Social Responsiveness Scale-Second Edition (SRS-2). Results identified non-significant and minimal differences (negligible-to-small) on the SRS-2 total, DSM-5 symptom subscale, and treatment subscale scores. Significant negative (moderate) correlations were found between the SRS-2 Social Cognition subscale and IQ and language scores and between the SRS-2 Social Motivation subscale and receptive language scores for females only; no significant correlations were found for males.

Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) is an aggressive infiltrative brain tumor with a particularly poor prognosis that is characterized by microvascular proliferation, necrotic tissue, and significant infiltration of M2-like monocytes. Compromised barrier function in tumor vasculature might be expected to permit communication between the tumor microenvironment and peripheral blood. METHODS: To ascertain whether tumor-derived vesicles and/or factors might reach the bloodstream and what effects these molecules have on the peripheral compartment, we analyzed blood samples collected from primary GBM patients. RESULTS: Notably, a significant number of patient sera samples contained tumor exosome-reactive immunoglobulin (Ig)G2 and IgG4 antibody isotypes, which are consistent with Th2 immunity. M2-like monocytes expressing CD14+ and CD163+, another indicator of Th2 bias, are elevated in GBM patient blood and associated with high serum concentrations of colony-stimulating factor 2 and 3, as well as interleukin-2, -4, and -13, the latter 2 cytokines being hallmarks of Th2 immunity. GBM patient sera samples induce high levels of CD163 expression when added to normal monocytes, providing mechanistic evidence of a basis for Th2 bias. Fractionation of GBM patient sera into samples enriched for exosomes or soluble factors proved that both fractions are capable of inducing CD163 expression in normal monocytes. CONCLUSIONS: The results of the current study indicate a Th2 bias in the periphery of GBM patients, likely as a result of products elaborated by the tumor. Consequentially, through immune modulation these brain tumors exert systemic effects beyond the confines of the CNS.

Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm.

Glioblastomas are primary intracranial tumors for which there is no cure. Patients receiving standard of care, chemotherapy and irradiation, survive approximately 15 months prompting studies of alternative therapies including vaccination. In a pilot study, a vaccine consisting of Lucite diffusion chambers containing irradiated autologous tumor cells pre-treated with an antisense oligodeoxynucleotide (AS-ODN) directed against the insulin-like growth factor type 1 receptor was found to elicit positive clinical responses in 8/12 patients when implanted in the rectus sheath for 24 h. Our preliminary observations supported an immune response, and we have since reopened a second Phase 1 trial to assess this possibility among other exploratory objectives. The current study makes use of a murine glioma model and samples from glioblastoma patients in this second Phase 1 trial to investigate this novel therapeutic intervention more thoroughly. Implantation of the chamber-based vaccine protected mice from tumor challenge, and we posit this occurred through the release of immunostimulatory AS-ODN and antigen-bearing exosomes. Exosomes secreted by glioblastoma cultures are immunogenic, eliciting and binding antibodies present in the sera of immunized mice. Similarly, exosomes released by human glioblastoma cells bear antigens recognized by the sera of 6/12 patients with recurrent glioblastomas. These results suggest that the release of AS-ODN together with selective release of exosomes from glioblastoma cells implanted in chambers may drive the therapeutic effect seen in the pilot vaccine trial.