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We evaluated the psychometric properties of the Trauma Informed Practice Scales – School Counseling Programs Version scores using item response theory with a sample of 270 school counselors. Participants ranged in age from 24 to 69 years (M = 42.82, SD = 9.96). Participants identified as female (81.5%), male (14.1%) or unreported (4.4%,). Participants' racial and ethnic backgrounds were: White (79.3%), African American or Black (5.6%), Multiracial (5.2%), Latino/Hispanic/Spanish (4.8%), American Indian/Alaskan Native (0.4%), Other (0.4%), or unreported (4.4%). Participants from 14 states completed an online survey, which included demographics questions and the TIPS-SCP. After removing the poorly performing items, partial credit model estimates explained 58.63% of the variance in participant responses. We found psychometric evidence to support its ability to capture trauma informed practices in schools and school counseling programs. The TIPS-SCP is a brief instrument to provide school counselors with a self-assessment of their trauma informed practices. The TIPS-SCP can aid school counselors in making data-informed decisions about immediate and future incorporations of integrating trauma informed practices into their schools and school counseling programs. [ABSTRACT FROM AUTHOR]

Objectives: Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. Methods: We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16 years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self‐reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. Results: The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: −0.025 (−0.048, −0.011), via loneliness (−0.011 [95% CI: −0.028, −0.002]), and via psychological distress (−0.017 [95% CI: −0.042, −0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. Conclusions: The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity. Key points: We evaluated whether psychosocial factors mediate the association between visual impairment and cognitive decline.With data from the Memory and Aging Project and the Minority Aging Research Study, we used structural equation models to estimate the total, direct, and indirect associations through each mediator (depressive symptoms, loneliness, lower social activity, and a latent variable, psychological distress, combining depressive symptoms and loneliness).We found evidence for partial mediation via social activity and loneliness. [ABSTRACT FROM AUTHOR]

Objectives: We previously described derivation and validation of the emergency department trigger tool (EDTT) for adverse event (AE) detection. As the first step in our multicenter study of the tool, we validated our computerized screen for triggers against manual review, establishing our use of this automated process for selecting records to review for AEs. Methods: This is a retrospective observational study of visits to three urban, academic EDs over 18 months by patients ≥ 18 years old. We reviewed 912 records: 852 with at least one of 34 triggers found by the query and 60 records with none. Two first‐level reviewers per site each manually screened for triggers. After completion, computerized query results were revealed, and reviewers could revise their findings. Second‐level reviewers arbitrated discrepancies. We compare automated versus manual screening by positive and negative predictive values (PPVs, NPVs), present population trigger frequencies, proportions of records triggered, and how often manual ratings were changed to conform with the query. Results: Trigger frequencies ranged from common (>25%) to rare (1/1000) were comparable at U.S. sites and slightly lower at the Canadian site. Proportions of triggered records ranged from 31% to 49.4%. Overall query PPV was 95.4%; NPV was 99.2%. PPVs for individual trigger queries exceeded 90% for 28–31 triggers/site and NPVs were >90% for all but three triggers at one site. Inter‐rater reliability was excellent, with disagreement on manual screening results less than 5% of the time. Overall, reviewers amended their findings 1.5% of the time when discordant with query findings, more often when the query was positive than when negative (47% vs. 23%). Conclusions: The EDTT trigger query performed very well compared to manual review. With some expected variability, trigger frequencies were similar across sites and proportions of triggered records ranged 31%–49%. This demonstrates the feasibility and generalizability of implementing the EDTT query, providing a solid foundation for testing the triggers' utility in detecting AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is predicted to be the second-highest cause of cancer mortality in the US by 2040. It is driven by various mutations including KRAS, TP53, SMAD4, and CDKN2A. Roughly 1 in 10 patients with pancreatic cancer have wildtype KRAS (KRASWT). We studied 27 patients with KRASWT to better understand their molecular characteristics and potential for precision medicine. Our findings revealed that KRASWT PDAC is enriched with potentially treatable genetic alterations, including those affecting the MAPK pathway, DNA repair pathway, and kinase fusion genes. One of our KRASWT PDAC patients was found to have a specific, targetable TFG-MET mutation and they responded well to treatment with a cMET inhibitor. This suggests that KRASWT PDAC has unique genetic characteristics that could be targeted with specific treatments tailored to each patient, highlighting the importance of comprehensive genetic profiling in KRASWT PDAC. Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics. [ABSTRACT FROM AUTHOR]

This study extends a previous one revising the VIA-Youth. Goals of the revision included reducing length and extending age range down to 8. After an initial revision, further discussion suggested the need for a more secular version of the spirituality scale. Based on evidence of changes in the understanding of spirituality during adolescence, separate sets of candidate items were generated for ages 8–12 and 13–17 with two overlapping items. The revised materials were administered to 94,487 youth online and through two school districts. Retaining the two overlapping items in both sets did not reduce fit. The result is two versions of the inventory for ages 8–12 (VIA-Y-1) and 13–17 (VIA-Y-2) that differ only on two items included in the spirituality scale. These offer a measure of spirituality in youth that is developmentally sensitive without relying on items referencing a religious framework. [ABSTRACT FROM AUTHOR]

Background: Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients' and physicians' real-world experiences with eptinezumab for chronic migraine (CM). Methods: REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. Results: Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported "good" days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. Conclusion: This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians. [ABSTRACT FROM AUTHOR]

Recent research has shown more favorable training adaptations for inactive adults when cardiorespiratory fitness (CRF) exercise is prescribed with the use of ventilatory thresholds compared to percentages of heart rate reserve (HRR). However, there is limited research on changes in health-related outcomes with the use of these CRF methods in combination with muscular fitness exercises. The objective of this study was to compare the effectiveness of two training programs for improving CRF, muscular fitness, and cardiometabolic risk factors. Inactive men and women (n=109, aged 49.3±15.5 years) were randomized to a non-exercise control group or one of two exercise training groups. The exercise training groups consisted of 13 weeks of structured exercise with progression using either CRF exercise prescribed with the use of ventilatory thresholds and functional training for muscular fitness (THRESH group) or HRR and traditional muscular fitness training (STND group). After the 13-week protocol, there were significant differences in body weight, body composition, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), VO2max, 5-repetition maximum (RM) bench press, and 5-RM leg press for both treatment groups compared to the control group after controlling for baseline values. However, the THRESH group had significantly more desirable outcomes for VO2max, 5-RM bench press, 5-RM leg press, body composition, and HDL-c when compared to both the STND and control group. Additionally, the proportion of individuals estimated as likely to respond above 3.5 mL½kg-1½min-1 in VO2max (i.e., the minimal clinically important difference) was 76.4%, 20.8%, and 0.13% for the THRESH, STND, and control groups, respectively. While both exercise programs elicited favorable health-related adaptations after 13 weeks, these results suggest that a personalized program with exercise prescribed based on ventilatory threshold and with the use of functional muscular fitness training may yield greater training adaptations. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Children hospitalized with a mental health crisis often receive pharmacologic restraint for management of acute agitation. We examined associations between pharmacologic restraint use and race and ethnicity among children admitted for mental health conditions to acute care nonpsychiatric children's hospitals. METHODS: We performed a retrospective cohort study of children (aged 5-≤18 years) admitted for a primary mental health condition from 2018 to 2022 at 41 US children's hospitals. Pharmacologic restraint use was defined as parenteral administration of medications for acute agitation. The association of race and ethnicity and pharmacologic restraint was assessed using generalized linear multivariable mixed models adjusted for clinical and demographic factors. Stratified analyses were performed based on significant interaction analyses between covariates and race and ethnicity. RESULTS: The cohort included 61 503 hospitalizations. Compared with non-Hispanic Black children, children of non-Hispanic White (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.72-0.92), Asian (aOR, 0.82; 95% CI, 0.68-0.99), or other race and ethnicity (aOR, 0.68; 95% CI, 0.57-0.82) were less likely to receive pharmacologic restraint. There was no significant difference with Hispanic children. When stratified by sex, racial/ethnic differences were magnified in males (aORs, 0.49-0.68), except for Hispanic males, and not found in females (aORs, 0.83-0.93). Sensitivity analysis revealed amplified disparities for all racial/ethnic groups, including Hispanic youth (aOR, 0.65; 95% CI, 0.47-0.91). CONCLUSIONS: Non-Hispanic Black children were significantly more likely to receive pharmacologic restraint. More research is needed to understand reasons for these disparities, which may be secondary to implicit bias and systemic and interpersonal racism. [ABSTRACT FROM AUTHOR]

Black Americans bear the greatest burden of HIV, accounting for 43% of new diagnoses. Yet Black Americans also evidence the lowest utilization rates of Pre-Exposure Prophylaxis (PrEP), a highly effective biomedical strategy for preventing HIV infection. Predictors of PrEP acceptance vary; however, little is known about psychological distress, such as post-traumatic stress disorder (PTSD) symptoms, as a predictor. In this cross-sectional study, n = 195 Black Americans, evidencing behaviors found in the research literature to heighten risk for contracting HIV (e.g. sex work, injection drug use) ages 18-29, 55% cisgender women, 39.5% cisgender men, 3% transgender/non-binary, completed audio-computer-assisted self-interviews. Bivariate analyses indicated significant positive associations between PTSD symptoms and PrEP acceptance and self-confidence. In multinomial logistic regression analyses, after controlling for Perceived HIV Risk, participants had a higher likelihood of responding they 'probably would' take PrEP (as opposed to 'definitely would not' take PrEP) if they reported higher levels of PTSD symptoms. Post-hoc analyses revealed a curvilinear relationship between PTSD symptoms and PrEP acceptance with those reporting the highest level of PTSD in the sample having slightly lower PrEP acceptance than those reporting moderately high levels of PTSD. Findings are discussed in the context of the negative impacts of high levels of PTSD and potential positive adaptations subsequent to moderate levels of PTSD that could be relevant to advances in HIV prevention efforts. [ABSTRACT FROM AUTHOR]

Speech that has been artificially accelerated through time compression produces a notable deficit in recall of the speech content. This is especially so for adults with cochlear implants (CI). At the perceptual level, this deficit may be due to the sharply degraded CI signal, combined with the reduced richness of compressed speech. At the cognitive level, the rapidity of time-compressed speech can deprive the listener of the ordinarily available processing time present when speech is delivered at a normal speech rate. Two experiments are reported. Experiment 1 was conducted with 27 normal-hearing young adults as a proof-of-concept demonstration that restoring lost processing time by inserting silent pauses at linguistically salient points within a time-compressed narrative ("time-restoration") returns recall accuracy to a level approximating that for a normal speech rate. Noise vocoder conditions with 10 and 6 channels reduced the effectiveness of time-restoration. Pupil dilation indicated that additional effort was expended by participants while attempting to process the time-compressed narratives, with the effortful demand on resources reduced with time restoration. In Experiment 2, 15 adult CI users tested with the same (unvocoded) materials showed a similar pattern of behavioral and pupillary responses, but with the notable exception that meaningful recovery of recall accuracy with time-restoration was limited to a subgroup of CI users identified by better working memory spans, and better word and sentence recognition scores. Results are discussed in terms of sensory-cognitive interactions in data-limited and resource-limited processes among adult users of cochlear implants. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our objective was to determine the accuracy of a point-of-care instrument, the Hospitalizations-Office Visits- Medical Conditions-Extra Care-Social Concerns (HOMES) instrument, in identifying patients with complex chronic conditions (CCCs) compared to an algorithm used to identify patients with CCCs within large administrative data sets. METHODS: We compared the HOMES to Feudtner's CCCs classification system. Using administrative algorithms, we categorized primary care patients at a children's hospital into 3 categories: no chronic conditions, non-complex chronic conditions, and CCCs. We randomly selected 100 patients from each category. HOMES scoring was completed for each patient. We performed an optimal cut-point analysis on 80% of the sample to determine which total HOMES score best identified children with ≥1 CCC and ≥2 CCCs. Using the optimal cut points and the remaining 20% of the study population, we determined the odds and area under the curve (AUC) of having ≥1 CCC and ≥2 CCCs. RESULTS: The median (interquartile range [IQR]) age was 4 (IQR: 0, 8). Using optimal cut points of ≥7 for ≥1 CCC and ≥11 for ≥2 CCCs, the odds of having ≥1 CCC was 19 times higher than lower scores (odds ratio [OR] 19.1 [95% confidence interval [CI]: 9.75, 37.5]) and of having ≥2 CCCs was 32 times higher (OR 32.3 [95% CI: 12.9, 50.6]). The AUCs were 0.76 for ≥1 CCC (sensitivity 0.82, specificity 0.80) and 0.74 for ≥2 CCCs (sensitivity 0.92, specificity 0.74). CONCLUSIONS: The HOMES accurately identified patients with CCCs. [ABSTRACT FROM AUTHOR]

Busulfan is an alkylating agent used as part of conditioning chemotherapy regimens prior to allogeneic hematopoietic cell transplant (allo‐HCT). Pharmacokinetic (PK)‐guided test‐dose strategies have been shown to improve the number of patients achieving busulfan exposure goals and improve clinical outcomes. However, current practices require extensive PK sampling. In this study, PK data were retrospectively collected from busulfan drug monitoring records from adult allo‐HCT recipients who received once‐daily intravenous busulfan at the University of North Carolina Medical Center (UNCMC). A population pharmacokinetic (popPK) model was developed to identify sources of interindividual variability and evaluate alternative PK sampling strategies. A 2‐compartment model, with covariate effects of actual body weight and sex, best described the data. The typical value of clearance for an 83 kg male was estimated to be 11.21 L/h. Fifty‐nine percent of allo‐HCT recipients were estimated to have met the UNCMC institutional myeloablative conditioning (MAC) exposure goal based on model post hoc estimates of clearance using all PK samples obtained following MAC dosing. Fifty‐seven percent of patients were estimated to have met this goal based on post hoc estimates using a single PK sample. Our results indicate once‐daily, intravenous busulfan PK in adult allo‐HCT recipients receiving MAC dosing can be reasonably described by a popPK model, and the use of a sparse PK sampling strategy may be feasible for determining target exposure attainment following MAC dosing. Use of a popPK model and sparse PK sampling strategy to carry out busulfan test‐dose procedures could reduce health care costs and inconvenience to patients. [ABSTRACT FROM AUTHOR]

Purpose: The Adverse Childhood Experiences (ACEs) screening tool captures some experiences of childhood adversity, ranging from abuse to parental separation. Research has shown a correlation between ACEs and both adult and childhood disease. This study evaluated the feasibility of conducting ACE screening in the pediatric intensive care unit (PICU) and investigated associations with markers for severity of illness and utilization of resources. Methods: This was a cross sectional study screening for ACEs among children admitted to a single quaternary medical-surgical PICU. Children age 0–18 years old admitted to the PICU over a one-year period were considered for enrollment. A 10-question ACE screen was used to evaluate children for exposure to ACEs. Chart review was used to collect demographic and clinical data. Results: Of the 432 parents approached for enrollment, 400 (92.6%) agreed to participate. Most parents reported an ACE score of zero (68.9%) while 31% of participants experienced at least 1 ACE, of whom 14.8% experienced ≥ 2 ACEs. There was not a statistically significant association between ACE score and length of stay (p-value = 0.26) or level of respiratory support in patients with asthma (p-value = 0.15) or bronchiolitis (p-value = 0.83). The primary reasons for not approaching families were parent availability, non-English speaking parents, and social work concerns. Conclusions: This study demonstrates feasibility to collect sensitive psychosocial data in the PICU and highlights challenges to enrollment. [ABSTRACT FROM AUTHOR]

Background: Studies using fast‐acting subcutaneous (SQ) insulin analogs in diabetic ketoacidosis (DKA) have demonstrated efficacy, safety, and cost‐effectiveness, allowing treatment of mild‐to‐moderate (MTM)‐severity DKA patients in non–intensive care unit (ICU) settings. However, emergency department (ED)‐based studies are few, with limited exploration of impacts on operational metrics. Methods: We implemented the SQuID (Subcutaneous Insulin in Diabetic Ketoacidosis) protocol for adults with MTM‐severity DKA in an urban academic ED, collecting data from August 1, 2021, to February 28, 2022. We examined fidelity (frequency of required q2h glucose checks), safety (proportion of patients administered rescue dextrose for hypoglycemia), and ED length of stay (EDLOS) for the SQuID cohort compared to patients (non‐ICU) treated with a traditional insulin infusion. We also examined ICU admission rate among MTM‐severity DKA patients after introduction of SQuID to two historical control periods (pre‐intervention and pre‐COVID). We used Mann–Whitney U to test for differences in EDLOS distributions, bootstrapped (n = 1000) confidence intervals (CIs) for EDLOS median differences, and the two‐sample z‐test for differences in ICU admissions. Results: We identified 177 MTM‐severity DKA patients in the study period (78 SQuID, 99 traditional cohort) and 163 preintervention and 161 pre‐COVID historical control patients. Fidelity to the SQuID pathway was good, with glucose checks exceeding the q2‐h requirement. We found no difference in the proportion of rescue dextrose administration compared to the traditional pathway. We observed significant reductions in median EDLOS for the SQuID cohort compared to the traditional cohort during the study period (−3.0, 95% CI −8.5 to −1.4), the preintervention period (−1.4, 95% CI −3.1 to −0.1), and the pre‐COVID control period (−3.6, 95% CI −7.5 to −1.8). Conclusions: In this single‐center study at an academic ED, treatment of patients with MTM‐severity DKA with a SQ insulin protocol was effective, demonstrated equivalent safety, and reduced ED length of stay. [ABSTRACT FROM AUTHOR]

Objectives The B-cell depleting biologic, rituximab, is used to treat refractory autoimmune myositis. However, the beneficial effects of rituximab appear to outweigh the known contribution of B cells in myositis. We aimed to elucidate how myositis patients respond differently to rituximab and possible alternative mechanisms of action. Methods Here we have: (i) comprehensively investigated concurrent mRNA and microRNA expression in muscle biopsies taken at baseline and 16 weeks post treatment in 10 patients who were part of the rituximab in myositis (RIM) trial; and (ii) investigated the beneficial effect of rituximab on myositis muscle cells. Results Our analyses identified an increased number of changes in gene expression in biopsies from patients who had a clinical response to rituximab (n  =   5) compared with non-responders (n  =   5). The two groups had completely different changes in microRNA and mRNA expression following rituximab therapy, with the exception of one mRNA, BHMT2. Networks of mRNA and microRNA with opposite direction of expression changes highlighted ESR1 as upregulated in responders. We confirmed ESR1 upregulation upon rituximab treatment of immortalized myotubes and primary human dermatomyositis muscle cells in vitro , demonstrating a direct effect of rituximab on muscle cells. Notably, despite showing a response to rituximab, human dermatomyositis primary muscle cells did not express the rituximab target, CD20. However, these cells expressed a possible alternative target of rituximab, sphingomyelinase-like phosphodiesterase 3 b (SMPDL3B). Conclusion In addition to B-cell depletion, rituximab may be beneficial in myositis due to increased ESR1 signalling mediated by rituximab binding to SMPDL3B on skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Objectives Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods In a prospective observational study, 475 patients with RA were treated with certolizumab (n  = 192) or adalimumab (n  = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P  = 0.04 and P  = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Background Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post–SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). Methods This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system–based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. Results The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P =.017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P <.001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. Conclusions Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515. [ABSTRACT FROM AUTHOR]

Background Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. Methods We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID−), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. Results Among the first 1000 participants, 722 were COVID+ and 278 were COVID−. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID− group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID− groups at 3 months. Conclusions Approximately half of COVID+ participants, as compared with one-quarter of COVID− participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. Clinical Trials Registration NCT04610515. [ABSTRACT FROM AUTHOR]

Background: Bereavement during childhood is associated with elevated rates of suicide‐related behaviours among youth. However, no interventions explicitly address suicidal ideation among bereaved youth. The Supporting Grieving Teens (SGT) programme was created as a preventive intervention to reduce suicide risk among bereaved youth. Methods: This preliminary open trial evaluated the feasibility, acceptability and preliminary outcomes of the SGT intervention among a sample of bereaved adolescents. Participants were 32 adolescents, 12–17 years of age (M = 14.44, SD = 1.56; 87.5% female, 31.3% Hispanic, 31.3% African American/Black and 25.0% non‐Hispanic White), seeking bereavement‐related services at a trauma and grief speciality outpatient clinic. Participants completed a two‐session web‐assisted intervention prior to enrolling in standard outpatient therapy. Results: There was a high rate of completion of the intervention, with 93.8% of those who provided assent completing both intervention sessions. Youth reported high levels of satisfaction with the intervention. Preliminary evaluation of outcomes demonstrated that the intervention was associated with small but significant reductions in thwarted belongingness and suicide ideation over the course of treatment and follow‐up. However, reliable change indices indicated reliable improvements for only a subset of participants. Limitations: This study utilised an open trial design without a control group, and so causality cannot be inferred. Additional limitations include the small sample size and limited variability in suicidal ideation in the sample. Conclusions: The intervention shows promise as a brief, web‐assisted psychosocial intervention for activating youths' existing social support networks. Further research is needed to more rigorously evaluate the intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: The migratory and invasive pathways that evolve in the early stage of colorectal cancer (CRC) are crucial in developing the metastatic cascade and drug resistance. Natural plant-based compounds and their active secondary metabolites selectively target several oncogenic and oncosuppressive signaling pathways. The anticancer mechanisms medicated by plant-based compounds can circumvent the associated side effects observed with chemotherapeutic agents. This study has developed a new potential anticancer therapeutic: casein-coated nanoparticles (NPs) encapsulating eugenol (EUG), a potent anti-metastatic molecule. The active form of matrix metalloproteinases (MMPs) predominantly releases at the leading edges of migrating tumor cells and can locally digest the "gatekeeping" casein coat of the EUG-carrying NPs and expose CRC cells to a high local concentration of EUG. Therefore, the targeted delivery of EUG by a "smart" nanoparticle can significantly improve its therapeutic index and minimize side effects on normal cells. This study is focused on the selective delivery and release of the plant-based anticancer compound eugenol (EUG) in colorectal cancer cells (CRC). EUG is an apoptotic and anti-growth compound in diverse malignant tumors, including CRC. However, EUG's rapid metabolization, excretion, and side effects on normal cells at higher dosages are major limitations of its therapeutic potential. To address this problem, we developed a "smart" enzyme-responsive nanoparticle (eNP) loaded with EUG that exposes tumors to a high level of the drug while keeping its concentration low among healthy cells. We demonstrated that EUG induces apoptosis in CRC cells irrespective of their grades in a dose- and time-dependent manner. EUG significantly decreases cancer cell migration, invasion, and the population of colon cancer stem cells, which are key players in tumor metastasis and drug resistance. The "smart" eNPs–EUG show a high affinity to cancer cells with rapid internalization with no affinity toward normal colon epithelial cells. NPs–EUG enhanced the therapeutic efficacy of EUG measured by a cell viability assay and showed no toxicity effect on normal cells. The development of eNPs–EUG is a promising strategy for innovative anti-metastatic therapeutics. [ABSTRACT FROM AUTHOR]

Background: As the population of older adults increases, appropriate deprescribing becomes increasingly important for emergency geriatric care. Older adults represent the sickest patients with chronic medical conditions, and they are often exposed to high‐risk medications. We need to provide an evidence‐based, standardized deprescribing program in the acute care setting, yet the evidence base is lacking and standardized medication programs are needed. Methods: We conducted a qualitative study with the goal to understand the perspective of healthcare workers, patients, and caregivers on deprescribing high‐risk medications in the context of emergency care practices, provider preferences, and practice variability, along with the facilitators and barriers to an effective deprescribing program in the emergency department (ED). To ensure rich, contextual data, the study utilized two qualitative methods: (1) a focus group with physicians, advanced practice providers, nurses, pharmacists, and geriatricians involved in care of older adults and their prescriptions in the acute care setting; (2) semi‐structured interviews with patients and caregivers involved in treatment and emergency care. Transcriptions were coded using thematic content analysis, and the principal investigator (S.L.) and trained research staff categorized each code into themes. Results: Data collection from a focus group with healthcare workers (n = 8) and semi‐structured interviews with patients and caregivers (n = 20) provided evidence of a potentially promising ED medication program, aligned with the vision of comprehensive care of older adults, that can be used to evaluate practices and develop interventions. We identified four themes: (1) Challenges in medication history taking, (2) missed opportunities in identifying high‐risk medications, (3) facilitators and barriers to deprescribing recommendations, and (4) how to coordinate deprescribing recommendations. Conclusions: Our focus group and semi‐structured interviews resulted in a framework for an ED medication program to screen, identify, and deprescribe high‐risk medications for older adults and coordinate their care with primary care providers. [ABSTRACT FROM AUTHOR]

Many professional chaplaincy organizations in the United States have board certified healthcare chaplains since the 1920s and documented how they have adapted their process as the profession has grown. In 2019, the Association of Professional Chaplains and the National Association of Catholic Chaplains sought the perspectives of key stakeholders about professional chaplaincy board certification. This study reports the results from 50 semi-structured interviews with certification candidates, certification committee members, and chaplaincy managers in the United States. Participants discussed the preparation of the certification application, the certification interview, the ease and difficulty of certification competencies, and the evolving workforce. This study demonstrated divergent views on many aspects of board certification, but participants predominately respected and valued the process. Chaplains with varying levels of experience discussed how board certification strengthens multidisciplinary respect and collaboration. Participants reported difficulties with competencies that required translating between theory and practice. [ABSTRACT FROM AUTHOR]

Objective: This study describes the prevalence of suicidal ideation (SI) during acute lymphoblastic leukemia (ALL) therapy and investigates the influence of clinical factors and physical symptoms on SI.Methods: The Children's Depressive Inventory (CDI-2) was administered to ALL patients (diagnosed 2012-2017) at start of consolidation, delayed intensification (DI), maintenance cycle 1 (MC1), and maintenance cycle 2 (MC2) in a multi-site study. SI was present if patients endorsed the item "I want to kill myself." Logistic regression models evaluated associations between SI and sociodemographic factors; depressive symptoms; and below average, average, and above average symptom clusters identified using latent class analysis of pain, nausea, fatigue, and sleep.Results: Participants (n = 175) were 51% male, 75% high-/very high-risk disease, with a median age of 11.2 years at diagnosis (range: 7-18 years). Overall, 14.9% of patients (75% under age 12 years) endorsed SI during treatment, including 4% at start of consolidation, 9% at DI, 8% at MC1, and 4% at MC2. Non-Hispanic Other patients were 10.9-times (95% CI: 2.30-53.40) more likely than non-Hispanic Whites to endorse SI (p = 0.003). The frequency of SI was higher in patients experiencing above average (53.3%) compared to below average (4.1%, p = 0.003) symptoms. Depressive symptoms were consistently associated with SI.Conclusions: SI during the initial year of childhood ALL was more prevalent in children under the age of 12 years, from ethnic groups not typically associated with increased risk, and who endorsed increased physical and depressive symptoms. Findings highlight the need for improved screening of mental health problems to mitigate symptoms of distress. [ABSTRACT FROM AUTHOR]

To provide evidence-based guidance specific to allied health and nursing practice for the assessment and management of individuals with Duchenne muscular dystrophy (DMD). Thirteen key focus areas were identified in consultation with health professionals and consumer advocacy groups. A series of systematic literature reviews were conducted to identify assessment and management strategies for each key focus area. A consensus process using modified Delphi methodology, including an Australia-New Zealand expert consensus meeting, was conducted. Recommendations underwent consultative review with key groups before being finalised and prepared for dissemination. This clinical practice guideline (CPG) generated 19 evidence-based recommendations, 117 consensus-based recommendations and five research recommendations across the 13 focus areas to inform allied health assessment and management of individuals with DMD. The resulting recommendations can be used in conjunction with existing medical CPGs to improve, standardise and advocate for allied health and rehabilitation care in DMD. The process used here may be useful for the development of CPGs in other rare diseases. Implementation-ready evidence-based statements to guide clinical care of individuals with DMD are provided with the potential to improve participation, function in the community and quality of life. A model for developing best practice statements for other rare neurological diseases is described. Allied health and nursing health professionals should focus research efforts to generate quality evidence to support rehabilitation practice. [ABSTRACT FROM AUTHOR]

The Grief Facilitation Inventory (GFI) is a newly-developed measure of caregiver behaviors theorized to facilitate or hinder children's adaptive grief reactions. We examine its factor structure, reliability, and validity. An exploratory factor analysis identified four factors: Ongoing Connection, Existential Continuity/Support, Caregiver Grief Expression, and Grief Inhibition/Avoidance. Both child- and caregiver-report versions had adequate-to-good internal consistency. The child-report GFI showed evidence of criterion-referenced validity via significant correlations with measures of child maladaptive grief and other psychological symptoms. Results provide preliminary evidence of the reliability, validity, and clinical utility of the GFI as a measure of caregiver grief-facilitation behaviors. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is underdiagnosed and undertreated in medical settings, in part due to a lack of AUD assessment instruments that are reliable and practical for use in routine care. This study evaluates the test‐retest reliability of a patient‐report Alcohol Symptom Checklist questionnaire when it is used in routine care, including primary care and mental health specialty settings. Methods: We performed a pragmatic test‐retest reliability study using electronic health record (EHR) data from Kaiser Permanente Washington, an integrated health system in Washington state. The sample included 454 patients who reported high‐risk drinking on a behavioral health screen and completed two Alcohol Symptom Checklists 1 to 21 days apart. Subgroups of these patients who completed both checklists in primary care (n = 271) or mental health settings (n = 79) were also examined. The primary measure was an Alcohol Symptom Checklist on which patients self‐reported whether they experienced each of the 11 AUD criteria within the past year, as defined by the Diagnostic and Statistical Manual of Mental Disorders‐5th edition (DSM‐5). Results: Alcohol Symptom Checklists completed in routine care and documented in EHRs had excellent test‐retest reliability for measuring AUD criterion counts (ICC = 0.79, 95% CI: 0.76 to 0.82). Test‐retest reliability estimates were also high and not significantly different for the subsamples of patients who completed both checklists in primary care (ICC = 0.82, 95% CI: 0.77 to 0.85) or mental health settings (ICC = 0.74, 95% CI: 0.62 to 0.83). Test‐retest reliability was not moderated by having a past two‐year AUD diagnosis, nor by the age or sex of the patient completing it. Conclusions: Alcohol Symptom Checklists can reliably and pragmatically assess AUD criteria in routine care among patients who screen positive for high‐risk drinking. The Alcohol Symptom Checklist may be a valuable tool in supporting AUD‐related care and monitoring AUD criteria longitudinally in routine primary care and mental health settings. [ABSTRACT FROM AUTHOR]

Background: Previous clinical studies have shown that psychological factors have significant effects on an athlete's readiness to return to sport after anterior cruciate ligament (ACL) reconstruction (ACLR). Hypothesis: We hypothesized that patients who underwent bridge-enhanced ACL restoration (BEAR) would have higher levels of psychological readiness to return to sport compared with patients who underwent ACLR. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 100 patients (median age, 17 years; median preoperative Marx activity score, 16) with complete midsubstance ACL injuries were randomized to either the BEAR procedure (n = 65) or autograft ACLR (n = 35 [33 hamstring and 2 bone--patellar tendon—bone]) and underwent surgery within 45 days of injury. Objective, functional, and patient-reported outcomes, including the ACL--Return to Sport after Injury (ACL-RSI) scale, were assessed at 6, 12, and 24 months postoperatively. Results: Patients who underwent the BEAR procedure had significantly higher ACL-RSI scores at 6 months compared with those who underwent ACLR (71.1 vs 58.2; P =.008); scores were similar at 12 and 24 months. Baseline factors independently predictive of higher ACL-RSI scores at 6 months were having a BEAR procedure and participating in level 1 sports prior to injury, explaining 15% of the variability in the scores. Regression analysis of baseline and 6-month outcomes as predictors indicated that the International Knee Documentation Committee (IKDC) score at 6 months explained 45% of the 6-month ACL-RSI variance. Subsequent analysis with IKDC excluded from the model indicated that decreased pain, increased hamstring and quadriceps strength in the surgical limb, and decreased side-to-side difference in anteroposterior knee laxity were significant predictors of a higher ACL-RSI score at 6 months, explaining 34% of the variability in scores. Higher ACL-RSI score at 6 months was associated with earlier clearance to return to sports. Conclusion: Patients who underwent the BEAR procedure had higher ACL-RSI scores at 6 months postoperatively. Better ACL-RSI scores at 6 months were related most strongly to higher IKDC scores at 6 months and were also associated with lower pain levels, better muscle recovery, and less knee laxity at 6 months. Registration: NCT02664545 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

In Aotearoa/New Zealand, sexuality education is one of seven key areas of learning in the Health and Physical Education (HPE) subject area within The New Zealand Curriculum. Since 2015, sexual diversity (lesbian, gay, bisexual identities and perspectives) and gender diversity (transgender; non-binary gender) have been explicitly included in the curriculum guidelines for teaching sexuality education in schools. Based on survey data collected from a convenience sample of 73 participants aged between 16 and 19 years, this study focused on the prevalence of sexuality education provision, its content, and the inclusion of sexuality and gender diversity in the wider school environment. Despite sexuality education being a mandatory part of HPE, only around three-quarters of respondents remembered having been taught it at some point in years 9 and 10. When taught, sexuality education was reported to focus primarily on conventional content areas (e.g. heterosex; biological function) and was therefore not inclusive of sexuality and gender diversity. Inclusion in the wider school environment was also limited, being mainly restricted to easy to implement measures (e.g. allowing same-sex partners at school balls and having a rainbow ally group). The implications of these findings for the development, wellbeing and human rights of young people are discussed. [ABSTRACT FROM AUTHOR]

Podocyte injury is important in development of diabetic nephropathy (DN). Although several studies have reported single-cell-based RNA sequencing (RNA-seq) of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN (T2DN) has not previously been compared with that of T1DN. We analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26fsTRAP; eNOS-/-; db/db mice and compared it with that of streptozotocin-induced T1DN in podocin-Cre; Rosa26fsTRAP; eNOS-/- mice using translating ribosome affinity purification (TRAP) and RNA-seq. More than 125 genes were highly enriched in the podocyte ribosome. More podocyte TRAP genes were differentially expressed in T2DN than in T1DN. TGF-β signaling pathway genes were upregulated, while MAPK pathway genes were downregulated only in T2DN, while ATP binding and cAMP-mediated signaling genes were downregulated only in T1DN. Genes regulating actin filament organization and apoptosis increased, while genes regulating VEGFR signaling and glomerular basement membrane components decreased in both type 1 and type 2 diabetic podocytes. A number of diabetes-induced genes not previously linked to podocyte injury were confirmed in both mouse and human DN. On the basis of differences and similarities in the podocyte translatome in T2DN and T1DN, investigators can identify factors underlying the pathophysiology of DN and novel therapeutic targets to treat diabetes-induced podocyte injury. [ABSTRACT FROM AUTHOR]

Introduction: A number of organizations publish comparisons of civilian health systems between countries. However, the authors were unable to find a global, systematic, and contemporary analysis of military healthcare systems. Although many databases exist for comparing national healthcare systems, the only such compilation of information for military medical systems is the Military Medical Almanac. A thorough review of the Almanac was conducted to understand the quality of information provided in each country's profile and to develop a framework for comparing between countries. This information is valuable because it can facilitate collaboration and lesson sharing between nations while providing a structured source of information about a nation's military medical capabilities for internal use.Materials and Methods: Each of the 142 profiles (submitted by 132 countries) published in the Almanac were reviewed. The information provided was extracted and aggregated into a spreadsheet that covered the broader categories of country background, force demographics, beneficiary populations, administration and oversight, physical structures and capabilities, research capabilities, and culture and artifacts. An initial sample of 20 countries was evaluated to test these categories and their subsections before the rest of the submissions were reviewed. Clear definitions were revised and established for each of the 69 subcategories. Qualitative and quantitative data were compiled in the spreadsheet to enable comparisons between entries.Results: Significant variation was found in how information was presented in country profiles and to what extent this was comparable between submissions. The most consistently provided information was in the country background, where the categories ranged from 90.15% to 100% completion across submissions. There was inconsistency in reporting of the numbers and types of healthcare workers employed within military medical services. Nearly 25% of nations reported providing medical care to family members of service members, but retirees, veterans, reservists, and law enforcement personnel were also mentioned. Some countries described organizational structures, military medical education institutions, and humanitarian operations. A few reported military medical research capabilities, though each research domain was present in 25% or less of all submissions. Interestingly, cultural identities such as emblems were present in nearly 90% of profiles, with many countries also having badges, symbols, and mottos.Conclusions: The Military Medical Almanac is potentially a highly valuable collection of publicly available baseline information on military medical services across the world. However, the quality of this collection is highly dependent on the submission provided by each country. It is recommended that the template for collecting information on each health system be refined, alongside an effort to increase awareness of the value of the Almanac as an opportunity to raise the international profile of each country's military medical system. This will ensure that the Almanac can better serve the international military medical community. [ABSTRACT FROM AUTHOR]

Rationale: Respiratory support (noninvasive ventilation or high-flow nasal cannula) applied at the time of extubation has been reported to reduce reintubation rates, but concerns regarding effectiveness have limited uptake into practice.Objectives: To determine if providing postextubation respiratory support to all patients undergoing extubation in a medical ICU would decrease the incidence of reintubation.Methods: We conducted a pragmatic, two-armed, cluster-crossover trial of adults undergoing extubation from invasive mechanical ventilation between October 1, 2017, and March 31, 2019, in the medical ICU of an academic medical center. Patients were assigned to either protocolized postextubation respiratory support (a respiratory therapist-driven protocol in which patients with suspected hypercapnia received noninvasive ventilation and patients without suspected hypercapnia received high-flow nasal cannula) or usual care (postextubation management at the discretion of treating clinicians). The primary outcome was reintubation within 96 hours of extubation.Measurements and Main Results: A total of 751 patients were enrolled. Of the 359 patients assigned to protocolized support, 331 (92.2%) received postextubation respiratory support compared with 66 of 392 patients (16.8%) assigned to usual care, a difference driven by differential use of high-flow nasal cannula (74.7% vs. 2.8%). A total of 57 patients (15.9%) in the protocolized support group experienced reintubation compared with 52 patients (13.3%) in the usual care group (odds ratio, 1.23; 95% confidence interval, 0.82 to 1.84; P = 0.32).Conclusions: Among a broad population of critically ill adults undergoing extubation from invasive mechanical ventilation at an academic medical center, protocolized postextubation respiratory support, primarily characterized by an increase in the use of high-flow nasal cannula, did not prevent reintubation compared with usual care.Clinical trial registered with www.clinicaltrials.gov (NCT0328831). [ABSTRACT FROM AUTHOR]

Background: The abundance of immune and stromal cells in the tumor microenvironment (TME) is informative of levels of inflammation, angiogenesis, and desmoplasia. Radiomics, an approach of extracting quantitative features from radiological imaging to characterize diseases, have been shown to predict molecular classification, cancer recurrence risk, and many other disease outcomes. However, the ability of radiomics methods to predict the abundance of various cell types in the TME remains unclear. In this study, we employed a radio-genomics approach and machine learning models to predict the infiltration of 10 cell types in breast cancer lesions utilizing radiomic features extracted from breast Dynamic Contrast Enhanced Magnetic Resonance Imaging.Methods: We performed a retrospective study utilizing 73 patients from two independent institutions with imaging and gene expression data provided by The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA), respectively. A set of 199 radiomic features including shape-based, morphological, texture, and kinetic characteristics were extracted from the lesion volumes. To capture one-to-one relationships between radiomic features and cell type abundance, we performed linear regression on each radiomic feature/cell type abundance combination. Each regression model was tested for statistical significance. In addition, multivariate models were built for the cell type infiltration status (i.e. "high" vs "low") prediction. A feature selection process via Recursive Feature Elimination was applied to the radiomic features on the training set. The classification models took the form of a binary logistic extreme gradient boosting framework. Two evaluation methods including leave-one-out cross validation and external independent test, were used for radiomic model learning and testing. The models' performance was measured via area under the receiver operating characteristic curve (AUC).Results: Univariate relationships were identified between a set of radiomic features and the abundance of fibroblasts. Multivariate models yielded leave-one-out cross validation AUCs ranging from 0.5 to 0.83, and independent test AUCs ranging from 0.5 to 0.68 for the multiple cell type invasion predictions.Conclusions: On two independent breast cancer cohorts, breast MRI-derived radiomics are associated with the tumor's microenvironment in terms of the abundance of several cell types. Further evaluation with larger cohorts is needed. [ABSTRACT FROM AUTHOR]

The Persistent Complex Bereavement Disorder (PCBD) Checklist was constructed to facilitate the developmentally sensitive assessment of proposed PCBD criteria in bereaved children and adolescents 8-18 years of age. Initial analyses of the PCBD Checklist provided support for the hypothesized two-factor model. The purpose of the present study was to evaluate the measurement invariance of the PCBD Checklist with respect to gender (boys and girls), race/ethnicity (White, Black, and Hispanic youth), and age (school age, preadolescent, and adolescent youth). Participants were 594 youth (50.4% female) aged 7-18 years (M = 11.91, SD = 2.80) who were evaluated as part of standard care at a community-based grief support center. Youth self-identified as Hispanic (n = 184, 30.8%), non-Hispanic white (n = 179, 30.0%), and African American/Black (n = 136, 22.8%). A series of stepwise, multigroup confirmatory factor analyses provided evidence in support of the PCBD Checklist's measurement invariance for all three groups concerning configural invariance, metric invariance, and scalar invariance. These results suggest that PCBD Checklist Criterion B and C scores are measuring similar latent variables, to a similar degree, across gender, race/ethnicity, and age. Establishing the cross-group equivalence of the PCBD Checklist is an important endorsement of its generalizability and clinical utility in that it can be administered to diverse populations with confidence that it is measuring proposed PCBC diagnostic criteria similarly across subgroups. [ABSTRACT FROM AUTHOR]

The Active Inhibition Scale (AIS; Ayers, Sandler, & Twohey, 1998) is an 11-item, self-report measure of emotional suppression among children and adolescents. Previous research with the AIS has linked emotional suppression to several clinically significant outcomes, such as posttraumatic stress symptoms (PTSS) and suicide, among trauma-exposed and bereaved youth; however, there are no published evaluations of its psychometric properties. We examined the factor structure and criterion validity of the AIS in two samples. Sample 1 included youth (M = 12.22 years, SD = 2.96, range: 6-18 years; 55.4% female) referred to an outpatient psychology clinic specializing in childhood trauma and grief. Sample 2 included youth (M = 13.18 years, SD = 2.58, range: 8-18 years; 61.8% female) referred to a community grief counseling center. Confirmatory factor analytic results supported a one-factor solution, Cronbach's α = .94. Additionally, AIS scores correlated positively with PTSS, depression, and maladaptive grief, rs = .43-.64. Evidence of factorial invariance was found across gender, race/ethnicity, and age group. Emotional suppression scores were higher among girls compared to boys, Black and Hispanic youth compared to White youth, and older compared to younger age groups. The magnitude of correlations between AIS and symptom measure scores was comparable across groups. These results support the reliability and criterion validity of the AIS with diverse youth populations and underscore the role that emotional suppression may play in explaining group differences in mental health symptoms. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicate that taste dysfunction occurs early in the development of Alzheimer's disease. It is debatable whether the deficit in taste is due primarily to peripheral sensory mechanisms or to central processing, or a combination of the two.Objective: The aim of our current study is to combine behavior and histological data in APP/PS1 transgenic mice to determine whether APP/PS1 transgenic mice show deficits in unconditioned taste preference and avoidance behaviors and whether taste impairments are due to defects in the peripheral taste system and/or problems with central processing of taste information.Methods: The APP/PS1 transgenic mutant mice were used as a model of Alzheimer's disease. We employed a brief-access gustometer test to assess immediate orosensory taste responses of APP/PS1 mice. We used immunohistochemistry to examine tongue, gustatory ganglion, and brain tissues to determine a cytological basis for behavioral deficits.Results: There is a significant, selective reduction of bitter taste sensitivity in APP/PS1 mice. These mice also have a loss of TRPM5-expressing taste receptor cells in the circumvallate papillae of the tongue. While we observed no overt loss of neuron cell bodies within the primary gustatory sensory neurons, degeneration of the neurons' peripheral axons innervating the taste bud may play a role in the observed loss of TRPM5-expressing taste receptor cells.Conclusion: This data supports a potential role for peripheral taste dysfunction in AD through the selective loss of taste receptor cells. Further study is necessary to delineate the mechanisms and pathological significance of this deficit in AD. [ABSTRACT FROM AUTHOR]

The National Training and Technical Assistance Center for Child, Youth, and Family Mental Health (NTTAC) supports the development and implementation of systems of care (SOC) for youth with serious emotional disorders (SED) and their families. This article presents results from a process evaluation of NTTAC, conducted to support the Center's quality improvement and contribute to the knowledge base around provision of technical assistance (TA). The evaluation used a mixed methods approach with data collection focused on a defined subset of NTTAC TA recipients-recipients of federal Comprehensive Community Mental Health Services for Children SOC grants. Data sources included coded administrative records from SOC grant sites, administrative data from NTTAC, standardized measures of SOC development, and stakeholder survey data. Results indicate that TA dosage matched needs and goals of TA recipients (SOC sites), overall levels of satisfaction with TA were high, and TA content was generally aligned with need. TA recipients reported significant progress on indicators of SOC development over time. Together, these findings suggest that it is possible to develop TA methods that reflect the level and type of TA recipients' goals and needs, and, in turn, positively impact SOC development and behavioral health service delivery. [ABSTRACT FROM AUTHOR]

Background: Most patients with substance use disorders (SUDs) never receive treatment and SUDs are under-recognized in primary care (PC) where patients can be treated or linked to treatment. Asking PC patients to directly report SUD symptoms on questionnaires might help identify SUDs but to our knowledge, this approach is previously untested.Objective: To describe the prevalence and severity of DSM-5 SUD symptoms reported by PC patients as part of routine care.Design: Cross-sectional study using secondary data.Participants: A total of 241,265 adult patients who visited one of 25 PC sites in an integrated health system in Washington state and had alcohol, cannabis, or other drug use screening documented in their EHRs (March 2015-July 2018) were included in main analyses if they had a positive screen for high-risk substance use defined as AUDIT-C score 7-12 points, or report of past-year daily cannabis use or any other drug use.Main Measures: The main outcome was number of SUD symptoms based on Diagnostic and Statistical Manual, 5th edition (DSM-5), reported on Symptom Checklists (0-11) for alcohol or other drugs: 2-3 mild; 4-5 moderate; 6-11 severe.Results: Of screened patients, 16,776 (5.7%) reported high-risk use of alcohol (2.4%), cannabis (3.9%), and/or other drugs (1.7%), and 65.0-69.9% of those completed Symptom Checklists. Of those with high-risk alcohol use, 52.5% (95% CI 50.9-54.0%) reported ≥ 2 symptoms consistent with mild-severe alcohol use disorders. Of those reporting daily cannabis use, 29.8% (28.6-30.9%) reported ≥ 2 symptoms consistent with mild-severe SUDs. Of those reporting any other drug use, 37.5% (35.7-39.3%) reported ≥ 2 symptoms consistent with mild-severe SUDs.Conclusions and Relevance: Many PC patients who screened positive for high-risk substance use reported symptoms consistent with DSM-5 SUDs on self-report Symptom Checklists. Use of SUD Symptom Checklists could support PC providers in making SUD diagnoses and initiating discussions of substance use. [ABSTRACT FROM AUTHOR]

Objective: MicroRNA (miRNA) are short noncoding RNA that regulate genes and are both biomarkers and mediators of disease. We used small RNA (sRNA) sequencing and machine learning methodology to develop an miRNA panel to reliably differentiate between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and control subjects.Methods: Plasma samples from 167 RA and 91 control subjects who frequency-matched for age, race, and sex were used for sRNA sequencing. TIGER was used to analyze miRNA. DESeq2 and random forest analyses were used to identify a prioritized list of miRNA differentially expressed in patients with RA. Prioritized miRNA were validated by quantitative PCR, and lasso and logistic regression were used to select the final panel of 6 miRNA that best differentiated RA from controls. The panel was validated in a separate cohort of 12 SLE, 32 RA, and 32 control subjects. Panel efficacy was assessed by area under the receiver operative characteristic curve (AUC) analyses.Results: The final panel included miR-22-3p, miR-24-3p, miR-96-5p, miR-134-5p, miR-140-3p, and miR-627-5p. The panel differentiated RA from control subjects in discovery (AUC = 0.81) and validation cohorts (AUC = 0.71), seronegative RA (AUC = 0.84), RA remission (AUC = 0.85), and patients with SLE (AUC = 0.80) versus controls. Pathway analysis showed upstream regulators and targets of panel miRNA are associated with pathways implicated in RA pathogenesis.Conclusion: An miRNA panel identified by a bioinformatic approach differentiated between RA or SLE patients and control subjects. The panel may represent an autoimmunity signature, perhaps related to inflammatory arthritis, which is not dependent on active disease or seropositivity. [ABSTRACT FROM AUTHOR]

Rationale: Administration of intravenous crystalloid solutions is a fundamental therapy for sepsis, but the effect of crystalloid composition on patient outcomes remains unknown.Objectives: To compare the effect of balanced crystalloids versus saline on 30-day in-hospital mortality among critically ill adults with sepsis.Methods: Secondary analysis of patients from SMART (Isotonic Solutions and Major Adverse Renal Events Trial) admitted to the medical ICU with an International Classification of Diseases, 10th Edition, Clinical Modification System code for sepsis, using multivariable regression to control for potential confounders.Measurements and Main Results: Of 15,802 patients enrolled in SMART, 1,641 patients were admitted to the medical ICU with a diagnosis of sepsis. A total of 217 patients (26.3%) in the balanced crystalloids group experienced 30-day in-hospital morality compared with 255 patients (31.2%) in the saline group (adjusted odds ratio [aOR], 0.74; 95% confidence interval [CI], 0.59-0.93; P = 0.01). Patients in the balanced group experienced a lower incidence of major adverse kidney events within 30 days (35.4% vs. 40.1%; aOR, 0.78; 95% CI, 0.63-0.97) and a greater number of vasopressor-free days (20 ± 12 vs. 19 ± 13; aOR, 1.25; 95% CI, 1.02-1.54) and renal replacement therapy-free days (20 ± 12 vs. 19 ± 13; aOR, 1.35; 95% CI, 1.08-1.69) compared with the saline group.Conclusions: Among patients with sepsis in a large randomized trial, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality compared with use of saline.Clinical trial registered with www.clinicaltrials.gov (NCT02444988). [ABSTRACT FROM AUTHOR]

Purpose: Transcutaneous electrical nerve stimulation (TENS) can reduce acute and chronic pain. Unilateral fatigue can produce discomfort in the affected limb and force and activation deficits in contralateral non-exercised muscles. TENS-induced local pain analgesia effects on non-local fatigue performance are unknown. Hence, the aim of the study was to determine if TENS-induced pain suppression would augment force output during a fatiguing protocol in the treated and contralateral muscles.Methods: Three experiments were integrated for this article. Following pre-tests, each experiment involved 20 min of TENS, sham, or a control condition on the dominant quadriceps. Then either the TENS-treated quadriceps (TENS_Treated) or the contralateral quadriceps (TENS_Contra) was tested. In a third experiment, the TENS and sham conditions involved two\; 100-s isometric maximal voluntary contractions (MVC) (30-s recovery) followed by testing of the contralateral quadriceps (TENS_Contra-Fatigue). Testing involved single knee extensors (KE) MVCs (pre- and post-test) and a post-test 30% MVC to task failure.Results: The TENS-treated study induced greater (p = 0.03; 11.0%) time to KE (treated leg) failure versus control. The TENS_Contra-Fatigue induced significant (p = 0.04; 11.7%) and near-significant (p = 0.1; 7.1%) greater time to contralateral KE failure versus sham and control, respectively. There was a 14.5% (p = 0.02) higher fatigue index with the TENS (36.2 ± 10.1%) versus sham (31.6 ± 10.6%) conditions in the second fatigue intervention set (treated leg). There was no significant post-fatigue KE fatigue interaction with the TENS_Contra.Conclusions: Unilateral TENS application to the dominant KE prolonged time to failure in the treated and contralateral KE suggesting a global pain modulatory response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lung expansion therapy is often ordered after surgery to improve alveolar ventilation and reduce risks of postoperative pulmonary complications. The impact of lung expansion therapy at altering ventilation in patients who are not intubated has not been described. The primary purpose of this study was to determine if there is a difference in dorsal redistribution of ventilation and incidences of postoperative pulmonary complications when comparing incentive spirometry (IS) with Ez-PAP lung expansion therapy after upper abdominal surgery. Our a priori null hypothesis was that there are no differences. METHODS: This randomized controlled trial enrolled adult human subjects after upper- abdominal surgery from January 2017 to November 2018. The subjects were allocated to receive IS or EzPAP 3 times a day on postoperative days 1-5. An electrical impedance tomography device was connected to the subjects for a single lung expansion therapy session on postoperative days 1, 3, and 5 to measure the change in post-lung expansion therapy dorsal end-expiratory lung impedance (ΔEELI%). Lung expansion therapy sessions with electrical impedance tomography included 2 min of normal breathing, 3 cycles of 10 breaths, and 2 min of normal breathing after cycle 3. Postoperative pulmonary complications were screened until hospital discharge. Mann-Whitney, chi-square, and Fisher exact tests were applied. Data were reported as count (n), percentage, and median (interquartile range) for primary and secondary outcomes. Alpha (2-tailed) was < 0.05. RESULTS: A total of 112 subjects were enrolled to receive IS (n = 56) or EzPAP (n = 56). Baseline characteristics were equal. Post-lung expansion therapy dorsal ΔEELI% increased for both groups, but the dorsal ΔEELI% for IS versus EzPAP on postoperative day 1 (16% versus 12%, P = .39), postoperative day 3 (6% versus 6%, P = .68), and postoperative day 5 (9% versus 6%, P = .46) was not significantly different. Hospital length of stay (4 d; P = .30) and incidence of postoperative pulmonary complications (3.6% versus 7.1%, P = .19) were similar. CONCLUSIONS: There was no significant post-lung expansion therapy dorsal ΔEELI% or postoperative pulmonary complications among the adults who received IS or EzPAP 3 times a day after upper abdominal surgery. (ClinicalTrials.gov registration NCT02892773.) [ABSTRACT FROM AUTHOR]

Background: Although the use of hip arthroscopy continues to increase, capsular management remains a controversial topic. Purpose: To investigate the biomechanical effect of capsulotomy and capsular repair techniques on hip joint kinematics in varying combinations of sagittal and coronal joint positions. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen hemi-pelvises (78.3 ± 6.0 years of age; 4 left, 6 male) were dissected of all overlying soft tissue, with the exception of the hip joint capsule. The femur was potted and attached to a load cell, while the pelvis was secured to a custom-designed fixture allowing static alteration of the flexion-extension arc. Optotrak markers were rigidly attached to the femur and pelvis to track motion of the femoral head with respect to the acetabulum. After specimen preparation, 7 conditions were tested: (1) intact, (2) after portal placement (anterolateral and midanterior), (3) interportal capsulotomy (IPC) (35 mm in length), (4) IPC repair, (5) T-capsulotomy (IPC +15-mm longitudinal incision), (6) partial T-repair (repair of longitudinal incision with IPC left open), (7) full T-repair. All conditions were tested in 15° of extension (–15°), 0°, 30°, 60°, and 90° of flexion. Additionally, all flexion angles were tested in neutral, as well as in specimen-specific maximum abduction and adduction, resulting in 15 testing positions. Internal rotation (IR) and external rotation (ER) moments of 3 N·m were manually applied to the femur via the load cell at each position. Rotational range of motion and joint kinematics were recorded. Results: In the neutral coronal plane, T-capsulotomy significantly increased IR/ER rotational range of motion compared with intact state at −15° (55.96°± 6.11° vs 44.92°± 7.35°, P <.001), while IPC significantly increased rotation compared with the portal state at 0° (60.09°± 6.82° vs 51.68°± 10.35°, P =.004). No statistically significant increases were found in mediolateral joint translation after IPC or T-capsulotomy. Similarly, no statistically significant increases were noted in anteroposterior translation after IPC or T-capsulotomy. Complete capsular repair restored near native joint kinematics, with no significant differences in rotation or translation between any complete capsular repair groups and the intact state, regardless of joint position. Conclusion: Universally, across all conditions, complete capsular repair after interportal or T-capsulotomy restored rotational range of motion and joint translation to values observed in the native joint. Clinical Relevance: Where feasible, complete capsular closure should be performed, especially after T-capsulotomy. However, further clinical evaluation is required to determine whether adverse kinematic parameters of an unrepaired capsule are associated with reduced patient-reported outcomes. [ABSTRACT FROM AUTHOR]

We examine changes in health insurance coverage and access to and utilization of health care before and after the national implementation of the Patient Protection and Affordable Care Act (ACA) among the U.S. adult immigrant population. Data from the 2011–2016 National Health Interview Survey are used to compare adult respondents in 2011–2013 (before the ACA implementation) and 2014–2016 (after the ACA implementation). Multivariable logistic regression analyses are used to compare changes over time. This study shows that the ACA has closed the coverage gap that previously existed between U.S. citizens and non-citizen immigrants. We find that naturalized citizens, non-citizens with more than 5 years of U.S. residency, and non-citizens with 5 years or less of U.S. residency reduced their probability of being uninsured by 5.81, 9.13, and 8.23%, respectively, in the first 3 years of the ACA. Improvements in other measures of access and utilization were also observed. [ABSTRACT FROM AUTHOR]

Background: Repetitive head impacts in young athletes are potentially detrimental to later life (e.g., age 50 + years) neurological function; however, it is unknown what the short-term effects (e.g., age 20 years) are in collegiate student-athletes.Objective: The purpose of this study was to determine the effect of the estimated age of first exposure to American tackle football participation on neurocognitive performance and symptom severity scores in collegiate student-athletes.Methods: We used a cohort study in which neurocognitive performance was assessed using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test in 4376 male athletes (age 19.3 ± 1.5 years, mass 96.3 ± 20.3 kg, height 185.0 ± 7.4 cm). Athletes were grouped by sport participation [American football (n = 3462) or non-contact (n = 914)] and estimated age of first exposure [< 12 years (n = 3022) or ≥ 12 years (n = 1354)]. The outcome measures were the four primary cognitive scores and the symptom severity score from ImPACT. We assessed primary outcomes across groups, controlling for age, learning accommodations, and concussion history.Results: Neurocognitive performance was not associated with the estimated age of first exposure-by-group interaction.Conclusion: Our findings indicate that participation in American tackle football before age 12 years does not result in neurocognitive deficits in college. Therefore, we suggest the following: the consequences of early exposure to repetitive head impacts do not manifest by college, the ImPACT test was not sensitive enough to identify the effects of an earlier estimated age of first exposure, or there is no association between an earlier estimated age of first exposure and neurocognitive functioning. Future longitudinal studies are warranted. [ABSTRACT FROM AUTHOR]

The identification of theoretically and empirically supported correlates of suicide ideation is important to improve treatment approaches to suicide. This study sought to examine the association between interpersonal trust (theoretically conceptualized as a distal risk marker) and suicide ideation in adolescence. Specifically, it was hypothesized that interpersonal trust would be negatively associated with suicide ideation via perceived burdensomeness and thwarted belongingness (conceptualized as more proximal risk markers). Data were drawn from a cross-sectional sample of 387 adolescent inpatients between the ages of 12 and 17 years (M = 14.72, SD = 1.49). The sample was 63.6% female, 37.5% Hispanic, 26.9% African American/Black, and 25.8% Caucasian. Adolescents completed a series of self-report measures to assess thwarted belongingness, perceived burdensomeness, interpersonal trust, depressive symptoms, and suicide ideation. A structural equation model was fit to the data, and results demonstrated a significant indirect path from interpersonal trust to suicide ideation via perceived burdensomeness, but not thwarted belongingness. Results suggest that interpersonal trust may be a distal risk marker for suicide ideation and that interventions to increase interpersonal trust may help prevent the development of thwarted belongingness, perceived burdensomeness, and suicide ideation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The analysis of health effects of exposure to mixtures is a critically important issue in human epidemiology, and increasing effort is being devoted to developing methods for this problem. A key feature of environmental mixtures is that some components can be highly correlated, raising the issues of confounding by coexposure and colinearity. A relatively unexplored topic in epidemiologic analysis of mixtures is the impact of residual confounding bias due to unmeasured or unknown variables. OBJECTIVES: This paper examines the potential amplification of such biases when correlated exposure variables are included in regression models. METHODS: We use directed acyclic graphs (DAGs) to describe different simple scenarios involving residual confounding. We derive expressions for the expected value of the resulting bias using linear models and multiple linear regression. RESULTS: Approaches to the analysis of mixtures that involve regressing the outcome on several exposures simultaneously can in some cases amplify rather than reduce confounding bias. DISCUSSIONS: The problem of bias amplification can worsen with stronger correlation between mixture components or when more mixture components are included in the model. CONCLUSIONS: Investigators must consider steps to minimize possible bias amplification in the design and analysis of epidemiologic studies of multiple correlated exposures. This may be particularly important when biomarkers of exposure are used. [ABSTRACT FROM AUTHOR]

Background: The creation of a single patient-reported outcome (PRO) platform validated across hip preservation, osteoarthritis (OA), and total hip arthroplasty (THA) populations may reduce barriers and streamline the routine collection of PROs in clinical practice. As such, the purpose of this study was to determine if augmenting the Hip disability and Osteoarthritis Outcome Score–Joint Replacement (HOOS, JR) with additional HOOS questions would result in a PRO platform that could be used across a wider spectrum of hip patient populations. Hypothesis: The HOOS, JR would demonstrate a notable ceiling effect, but by augmenting the HOOS, JR with additional HOOS questions, a responsive PRO platform could be created. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Using preoperative and postoperative HOOS responses from a sample of 304 patients undergoing periacetabular osteotomy (PAO), additional items were identified to augment the HOOS, JR. The psychometric properties of a newly created PRO tool (HOOSglobal) were then compared with the HOOS, JR and other PRO instruments developed for patients with hip OA and/or undergoing THA. Results: By augmenting the HOOS, JR with 2 additional questions, the HOOSglobal was more responsive than all other included PRO tools and had significantly fewer maximum postoperative scores than the HOOS, JR (P < .0001), HOOS–Physical Function Short form (P < .0001), Western Ontario and McMaster Universities Osteoarthritis Index (P = .02), University of California, Los Angeles activity scale (P = .0002), and modified Harris Hip Score (P = .04). The postoperative HOOSglobal score threshold associated with patients achieving the patient acceptable symptom state (PASS) was 62.5. Conclusion: The HOOSglobal is a valid and responsive PRO tool after PAO and may potentially provide the orthopaedic community with a PRO platform to be used across hip-related subspecialties. For patients undergoing PAO, a postoperative HOOSglobal score ≥62.5 was associated with patients achieving the PASS. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to evaluate if and how neuropsychiatric symptoms (NPS) of dementia influence the management and disposition of older adults who present to emergency care settings.Methods: This is a retrospective cohort study that involved the medical and psychiatric emergency departments of a tertiary academic medical center. Participants included patients ≥65 years of age with dementia who presented between 1 February 2012 and 16 July 2014 (n = 347). Subjects with documented NPS (n = 78) were compared with a group of subjects without documented NPS (n = 78) randomly selected from the overall group with dementia. The groups with and without NPS were compared on demographic, clinical, management, and disposition characteristics.Results: Patients with NPS were more likely to have additional diagnostic testing performed and receive psychotropic medications including benzodiazepines and antipsychotics. Significantly fewer patients with NPS (59.0%) returned to their original setting from the emergency department than patients without NPS (76.9%). Among patients with NPS, those who had a motor disturbance were more likely to receive psychotropic medications than patients who did not have a motor disturbance. Depression/dysphoria, anxiety, disinhibition, irritability/lability, and motor disturbance were all associated with transfer from medical to psychiatric emergency department. Patients with depression/dysphoria or anxiety were more likely to be psychiatrically hospitalized.Conclusions: There are significant differences in the management of dementia with and without NPS in the emergency room setting. Developing and implementing successful methods to manage NPS in the emergency department and outpatient setting could potentially lead to less emergent psychotropic administration and reduce hospitalizations. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sentinel is a program sponsored by the US Food and Drug Administration to monitor the safety of medical products. We conducted a cohort assessment to evaluate the ability of the Sentinel Propensity Score Matching Tool to reproduce in an expedited fashion the known association between glyburide (vs. glipizide) and serious hypoglycemia. Thirteen data partners who contribute to the Sentinel Distributed Database participated in this analysis. A pretested and customizable analytic program was run at each individual site. De-identified summary results from each data partner were returned and aggregated at the Sentinel Operations Center. We identified a total of 198,550 and 379,507 new users of glyburide and glipizide, respectively. The incidence of emergency department visits and hospital admissions for serious hypoglycemia was 19 per 1000 person-years (95% confidence interval = 17.9, 19.7) for glyburide users and 22 (21.6, 22.7) for glipizide users. In cohorts matched by propensity score based on predefined variables, the hazard ratio (HR) for glyburide was 1.36 (1.24, 1.49) versus glipizide. In cohorts matched on a high-dimensional propensity score based on empirically selected variables, for which the program ran to completion in five data partners, the HR was 1.49 (1.31, 1.70). In cohorts matched on propensity scores based on both predefined and empirically selected variables via the high-dimensional propensity score algorithm (the same five data partners), the HR was 1.51 (1.32, 1.71). These findings are consistent with the literature, and demonstrate the ability of the Sentinel Propensity Score Matching Tool to reproduce this known association in an expedited fashion.See video abstract at, http://links.lww.com/EDE/B275. [ABSTRACT FROM AUTHOR]

Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-Lipoxygenase (12/15-LOX) is induced in β-cells and macrophages during T1D and produces proinflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling has suggested reduced promiscuity of ML351 compared with ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of proinflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced β-cell oxidative stress, and preservation of β-cell mass. In the nonobese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced β-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in insulitis. The data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of β-cell dysfunction and glycemic deterioration in models of T1D. [ABSTRACT FROM AUTHOR]