Publications by authors named "Richard González"

181 Publications

Trends in utilization of whole-body computed tomography in blunt trauma after MVC: Analysis of the Trauma Quality Improvement Program database.

J Trauma Acute Care Surg 2021 Jun;90(6):951-958

From the Burn and Shock Trauma Research Institute (C.B., R.G., F.A.L.), Loyola University Chicago, Chicago; Department of Surgery (C.B., B.R., P.P., M.B., R.G., F.A.L.), Department of Thoracic and Cardiovascular Surgery (Z.M.A.), Loyola University Medical Center, Maywood; and Edward Hines Jr. Veterans Affair Hospital (M.B., Z.M.A., F.A.L.), Hines, Illinois.

Background: The use of whole-body computed tomography (WBCT) in awake, clinically stable injured patients is controversial. It is associated with unnecessary radiation exposure and increased cost. We evaluate use of computed tomography (CT) imaging during the initial evaluation of injured patients at American College of Surgeons Levels I and II trauma centers (TCs) after blunt trauma.

Methods: We identified adult blunt trauma patients after motor vehicle crash (MVC) from the American College of Surgeons Trauma Quality Improvement Program (TQIP) database between 2007 and 2016 at Level I or II TCs. We defined awake clinically stable patients as those with systolic blood pressure of 100 mm Hg or higher with a Glasgow Coma Scale score of 15. Computed tomography imaging had to have been performed within 2 hours of arrival. Whole-body computed tomography was defined as simultaneous CT of the head, chest and abdomen, and selective CT if only one to two aforementioned regions were imaged. Patients were stratified by Injury Severity Score (ISS).

Results: There were 217,870 records for analysis; 131,434 (60.3%) had selective CT, and 86,436 (39.7%) had WBCT. Overall, there was an increasing trend in WBCT utilization over the study period (p < 0.001). In patients with ISS less than 10, WBCT was utilized more commonly at Level II versus Level I TCs in patients discharged from the emergency department (26.9% vs. 18.3%, p < 0.001), which had no surgical procedure(s) (81.4% vs. 80.3%, p < 0.001) and no injury of the head (53.7% vs. 52.4%, p = 0.008) or abdomen (83.8% vs. 82.1%, p = 0.001). The risk-adjusted odds of WBCT was two times higher at Level II TC vs. Level I (odds ratio, 1.88; 95% confidence interval 1.82-1.94; p < 0.001).

Conclusion: Whole-body computed tomography utilization is increasing relative to selective CT. This increasing utilization is highest at Level II TCs in patients with low ISSs, and in patients without associated head or abdominal injury. The findings have implications for quality improvement and cost reduction.

Level Of Evidence: Care management, Level IV.
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http://dx.doi.org/10.1097/TA.0000000000003129DOI Listing
June 2021

Bouncing behavior of sub-four minute milers.

Sci Rep 2021 May 18;11(1):10501. Epub 2021 May 18.

School of Kinesiology, University of Michigan, 1402 Washington Heights, Ann Arbor, MI, 48109-2013, USA.

Elite middle distance runners present as a unique population in which to explore biomechanical phenomena in relation to running speed, as their training and racing spans a broad spectrum of paces. However, there have been no comprehensive investigations of running mechanics across speeds within this population. Here, we used the spring-mass model of running to explore global mechanical behavior across speeds in these runners. Ten elite-level 1500 m and mile runners (mean 1500 m best: 3:37.3 ± 3.6 s; mile: 3:54.6 ± 3.9 s) and ten highly trained 1500 m and mile runners (mean 1500 m best: 4:07.6 ± 3.7 s; mile: 4:27.4 ± 4.1 s) ran on a treadmill at 10 speeds where temporal measures were recorded. Spatiotemporal and spring-mass characteristics and their corresponding variation were calculated within and across speeds. All spatiotemporal measures changed with speed in both groups, but the changes were less substantial in the elites. The elite runners ran with greater approximated vertical forces (+ 0.16 BW) and steeper impact angles (+ 3.1°) across speeds. Moreover, the elites ran with greater leg and vertical stiffnesses (+ 2.1 kN/m and + 3.6 kN/m) across speeds. Neither group changed leg stiffness with increasing speeds, but both groups increased vertical stiffness (1.6 kN/m per km/h), and the elite runners more so (further + 0.4 kN/m per km/h). The elite runners also demonstrated lower variability in their spatiotemporal behavior across speeds. Together, these findings suggested that elite middle distance runners may have distinct global mechanical patterns across running speeds, where they behave as stiffer, less variable spring-mass systems compared to highly trained, but sub-elite counterparts.
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http://dx.doi.org/10.1038/s41598-021-89858-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131362PMC
May 2021

Targeted self-regulation interventions in low-income children: Clinical trial results and implications for health behavior change.

J Exp Child Psychol 2021 Aug 25;208:105157. Epub 2021 Apr 25.

School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.

Self-regulation, known as the ability to harness cognitive, emotional, and motivational resources to achieve goals, is hypothesized to contribute to health behaviors across the lifespan. Enhancing self-regulation early in life may increase positive health outcomes. During pre-adolescence, children assume increased autonomy in health behaviors (e.g., eating; physical activity), many of which involve self-regulation. This article presents results from a clinical trial (NCT03060863) that used a factorial design to test behavioral interventions designed to enhance self-regulation, specifically targeting executive functioning, emotion regulation, future-oriented thinking, and approach biases. Participants were 118 children (9-12 years of age, M = 10.2 years) who had a history of living in poverty. They were randomized to receive up to four interventions that were delivered via home visits. Self-regulation was assayed using behavioral tasks, observations, interviews, and parent- and child-report surveys. Results were that self-regulation targets were reliably assessed and that interventions were delivered with high fidelity. Intervention effect sizes were very small to moderate (d range = .02-.65, median = .14), and most were not statistically significant. Intercorrelation analyses indicated that associations between measures within each target varied based on the self-regulation target evaluated. Results are discussed with regard to the role of self-regulation-focused interventions in child health promotion. Implications of findings are reviewed for informing next steps in behavioral self-regulation interventions among children from low-income backgrounds.
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http://dx.doi.org/10.1016/j.jecp.2021.105157DOI Listing
August 2021

Comparison and interpretability of machine learning models to predict severity of chest injury.

JAMIA Open 2021 Jan 1;4(1):ooab015. Epub 2021 Mar 1.

Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.

Objective: Trauma quality improvement programs and registries improve care and outcomes for injured patients. Designated trauma centers calculate injury scores using dedicated trauma registrars; however, many injuries arrive at nontrauma centers, leaving a substantial amount of data uncaptured. We propose automated methods to identify severe chest injury using machine learning (ML) and natural language processing (NLP) methods from the electronic health record (EHR) for quality reporting.

Materials And Methods: A level I trauma center was queried for patients presenting after injury between 2014 and 2018. Prediction modeling was performed to classify severe chest injury using a reference dataset labeled by certified registrars. Clinical documents from trauma encounters were processed into concept unique identifiers for inputs to ML models: logistic regression with elastic net (EN) regularization, extreme gradient boosted (XGB) machines, and convolutional neural networks (CNN). The optimal model was identified by examining predictive and face validity metrics using global explanations.

Results: Of 8952 encounters, 542 (6.1%) had a severe chest injury. CNN and EN had the highest discrimination, with an area under the receiver operating characteristic curve of 0.93 and calibration slopes between 0.88 and 0.97. CNN had better performance across risk thresholds with fewer discordant cases. Examination of global explanations demonstrated the CNN model had better face validity, with top features including "contusion of lung" and "hemopneumothorax."

Discussion: The CNN model featured optimal discrimination, calibration, and clinically relevant features selected.

Conclusion: NLP and ML methods to populate trauma registries for quality analyses are feasible.
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http://dx.doi.org/10.1093/jamiaopen/ooab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935500PMC
January 2021

Adrenocortical interdependence in father-infant and mother-infant dyads: Attunement or something more?

Dev Psychobiol 2021 Feb 21. Epub 2021 Feb 21.

Department of Psychology, University of Michigan, Ann Arbor, MI, USA.

Father-infant and mother-infant (one-year-olds) adrenocortical attunement was explored during the Strange Situation Procedure (SSP) among 125 father-infant and 141 mother-infant dyads. Cortisol was assessed at baseline (T1), 20 (T2), and 40 minutes (T3) after the first parent-infant separation. Initial correlations indicated significant associations between father-infant and mother-infant cortisol at each time. Cortisol interdependence was further explored using Actor-Partner Interdependence Models. There was no evidence supporting cortisol interdependence based on within-time residual correlations between parent-infant cortisol, once stability and cross-lagged paths were controlled. Infant cortisol at T2 predicted T3 cortisol for fathers and mothers resulting in a series of follow-up exploratory analyses to examine mediating processes which revealed that infant distress during the SSP predicted infant T2 cortisol, which, in turn, predicted infant negativity during the 15-min mother-infant teaching task that followed the SSP. Among father-infant dyads, infant T2 cortisol predicted infant negativity during father-infant interaction, with infants expressing more negativity having less sensitive fathers. Findings provide little support of parent-infant adrenocortical attunement across either father-infant or mother-infant dyads during the SSP, but preliminary evidence indicates infant distress as a potential mediator. Future research may want to focus on affective and behavioral processes that underlie the concept of parent-infant adrenocortical attunement.
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http://dx.doi.org/10.1002/dev.22110DOI Listing
February 2021

Assessment of Cognitive-Motor Performance Costs, Task Prioritization, and Adaptation to Dishwashing Under Increased Demand in Older Women With Arthritis.

Innov Aging 2021 27;5(1):igaa059. Epub 2020 Nov 27.

Institute for Social Research, University of Michigan, Ann Arbor, Michigan, US.

Background And Objectives: Hand arthritis can limit upper-limb instrumental activities of daily living (IADLs) and require the recruitment of additional cognitive and motor resources to support performance. We devised a dual-task protocol for dishwashing to examine cognitive-motor performance costs and prioritizations under increased demands, processes of adaptation, and individual differences in performance costs.

Research Design And Methods: Sixty women with hand arthritis (aged 60-91) completed a standardized dishwashing protocol. Motor demand was increased via the properties of the soap dispenser. Cognitive demand was increased using audial attention and response inhibition tasks. The protocol was completed twice per lab visit on 3 occasions. Response time and dishwashing time provided measures of cognitive and motor task performance. Prioritization was determined by comparing the magnitude of dual-task cost (DTC) across tasks. Adaptation to the dishwashing protocol and novel dispenser was assessed by change in DTC across lab visits. Individual differences in cognitive and physical ability were assessed with the trail making B test and gait speed.

Results: Estimates from linear mixed-effects models revealed that response time increased, whereas dishwashing time decreased, during the dual-task study stages. Cognitive-motor prioritization effects were most pronounced among women with lower cognitive and physical ability. Evidence of prioritization and individual differences in DTC diminished across lab visits.

Discussion And Implications: The pattern of results suggests that older women with arthritis prioritize the motor over cognitive components of dishwashing, a common IADL. Adaptation across lab visits resulted in improved performance, reduced evidence of prioritization, and attenuated differences in DTC across physical and cognitive abilities.
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http://dx.doi.org/10.1093/geroni/igaa059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874570PMC
November 2020

Improving spring-mass parameter estimation in running using nonlinear regression methods.

J Exp Biol 2021 Mar 18;224(Pt 6). Epub 2021 Mar 18.

School of Kinesiology, University of Michigan, 1402 Washington Heights, Ann Arbor, MI 48109-2013, USA.

Runners are commonly modeled as spring-mass systems, but the traditional calculations of these models rely on discrete observations during the gait cycle (e.g. maximal vertical force) and simplifying assumptions (e.g. leg length), challenging the predicative capacity and generalizability of observations. We present a method to model runners as spring-mass systems using nonlinear regression (NLR) and the full vertical ground reaction force (vGRF) time series without additional inputs and fewer traditional parameter assumptions. We derived and validated a time-dependent vGRF function characterized by four spring-mass parameters - stiffness, touchdown angle, leg length and contact time - using a sinusoidal approximation. Next, we compared the NLR-estimated spring-mass parameters with traditional calculations in runners. The mixed-effect NLR method (ME NLR) modeled the observed vGRF best (RMSE:155 N) compared with a conventional sinusoid approximation (RMSE: 230 N). Against the conventional methods, its estimations provided similar stiffness approximations (-0.2±0.6 kN m) with moderately steeper angles (1.2±0.7 deg), longer legs (+4.2±2.3 cm) and shorter effective contact times (-12±4 ms). Together, these vGRF-driven system parameters more closely approximated the observed vertical impulses (observed: 214.8 N s; ME NLR: 209.0 N s; traditional: 223.6 N s). Finally, we generated spring-mass simulations from traditional and ME NLR parameter estimates to assess the predicative capacity of each method to model stable running systems. In 6/7 subjects, ME NLR parameters generated models that ran with equal or greater stability than traditional estimates. ME NLR modeling of the vGRF in running is therefore a useful tool to assess runners holistically as spring-mass systems with fewer measurement sources or anthropometric assumptions. Furthermore, its utility as statistical framework lends itself to more complex mixed-effects modeling to explore research questions in running.
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http://dx.doi.org/10.1242/jeb.232850DOI Listing
March 2021

Internal and External Validation of an Alcohol Biomarker for Screening in Trauma.

Ann Surg 2021 Mar 10. Epub 2021 Mar 10.

Division of Pulmonary and Critical Care Medicine, University of Wisconsin, Madison, WI Clinical Research Office, Stritch School of Medicine, Loyola University Chicago, Maywood, IL Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco Hospital and Trauma Center, University of California San Francisco, San Francisco, CA (ER and CMH) Burn Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO Division of Trauma Surgery, University of California Davis Medical Center, Sacramento, CA Division of Trauma Surgery and Critical Care Medicine, Zuckerberg San Francisco Hospital and Trauma Center, University of California San Francisco, San Francisco, CA (LZK and RAC) Burn Research, Alcohol Research Programs, Division of GI, Trauma and Endocrine Surgery, Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.

Objective: We aimed to examine biomarkers for screening unhealthy alcohol use in the trauma setting.

Summary And Background Data: Self-report tools are the practice standard for screening unhealthy alcohol use; however, their collection suffers from recall bias and incomplete collection by staff.

Methods: We performed a multi-center prospective clinical study of 251 adult patients who arrived within 24 hours of injury with external validation in another 60 patients. The Alcohol Use Disorders Identification Test served as the reference standard. The following biomarkers were measured: (1) phosphatidylethanol (PEth); (2) ethyl glucuronide; (3) ethyl sulfate; (4) gamma-glutamyl-transpeptidase; (5) carbohydrate deficient transferrin; and (6) blood alcohol concentration (BAC). Candidate single biomarkers and multivariable models were compared by considering discrimination (AUROC). The optimal cutpoint for the final model was identified using a criterion for setting the minimum value for specificity at 80% and maximizing sensitivity. Decision curve analysis was applied to compare to existing screening with BAC.

Results: PEth alone had an AUROC of 0.93 (95% CI: 0.92-0.93) in internal validation with an optimal cutpoint of 25 ng/mL. A 4-variable biomarker model as well as the addition of any single biomarker to PEth did not improve AUROC over PEth alone (p > 0.05). Decision curve analysis showed better performance of PEth over BAC across most predicted probability thresholds. In external validation, sensitivity and specificity were 76.0% (95% CI: 53.0%-92.0%) and 73.0% (95% CI: 56.0%-86.0%), respectively.

Conclusion And Relevance: PEth alone proved to be the single best biomarker for screening of unhealthy alcohol use and performed better than existing screening systems with BAC. PEth may overcome existing screening barriers.
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http://dx.doi.org/10.1097/SLA.0000000000004770DOI Listing
March 2021

Don't touch: Developmental trajectories of toddlers' behavioral regulation related to older siblings' behaviors and parental discipline.

Soc Dev 2020 Nov 10;29(4):1031-1050. Epub 2020 Feb 10.

Department of Psychology University of Michigan Ann Arbor MI USA.

Behavioral regulation is one of the key developmental skills children acquire during early childhood. Previous research has focused primarily on the role of parents as socializing agents in this process, yet it is likely that older siblings also are influential given the numerous daily interactions between siblings. This exploratory longitudinal study investigated developmental heterogeneity in behavioral regulation during toddlerhood and the early preschool years (18 to 36 months) and relations with older siblings' control and behavioral regulation while taking into account parental discipline. Toddlers were visited at home at 18, 24, and 36 months and observed during a gift-delay task with their older sibling in 93 families. Behavioral regulation of both siblings and gentle and harsh control of the older sibling were coded during the sibling gift-delay task, which was validated using parent-reports of toddlers' internalized conduct. Analyses revealed five distinct developmental trajectories among toddlers' behavioral regulation, revealing different patterns of developmental multifinality and equifinality. Older siblings' harsh control and parental discipline differed across toddler trajectory groups. Older siblings' behaviors covaried with the toddlers' behavioral regulation suggesting that older siblings may be acting as models for younger siblings, as well as disciplining and teaching toddlers to resist temptation.
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http://dx.doi.org/10.1111/sode.12440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687271PMC
November 2020

Prediction of severe chest injury using natural language processing from the electronic health record.

Injury 2021 Feb 25;52(2):205-212. Epub 2020 Oct 25.

Center for Health Outcomes and Informatics Research, Health Sciences Division, Loyola University Chicago, CTRE Building 115, Room 126, 2160 South 1st Avenue, Maywood, IL, United States; Department of Health Informatics and Data Science, Loyola University Chicago, 2160 South First Avenue, Maywood, IL, United States.

Introduction: Trauma injury severity scores are currently calculated retrospectively from the electronic health record (EHR) using manual annotation by certified trauma coders. Natural language processing (NLP) of clinical documents in the EHR may enable automated injury scoring. We hypothesize that NLP with machine learning can discriminate between cases of severe and non-severe injury to the thorax after trauma.

Methods: Clinical documents from a trauma center were examined between 2014 and 2018. Severe chest injury was defined as a thorax abbreviated injury score (AIS) >2 and served as the reference standard for supervised learning. Free text unigrams and concept unique identifiers (CUIs) from the Unified Medical Language Systems (UMLS) were extracted from clinical documents collected at one hour, four hours, and eight hours after patient arrival to the emergency department. Logistic regression models with elastic net regularization were tuned to maximize area under the receiver operating characteristic curve (AUROC) using 10-fold cross-validation on the training dataset (80%) and tested on a hold-out 20% dataset.

Results: There were 6,891 traumas that met inclusion criteria. The complete data corpus consisted of 473,694 documents. Models trained using the first hour of data had a mean AUROC of 0.88 (95%CI [0.86, 0.89]); model discrimination and reclassification from the first hour significantly improved after eight hours with a mean AUROC of 0.94 (95%CI [0.93, 0.95]). Performance of models using CUIs were similar to unigrams (p>0.05). Models demonstrated excellent clinical face validity.

Conclusions: Both CUIs and unigrams demonstrated excellent discrimination in predicting severity of chest injury using the first eight hours of clinical documents. Our model demonstrates that automated anatomical injury scoring is feasible and may be used for aggregation of data for trauma research and quality programs.
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http://dx.doi.org/10.1016/j.injury.2020.10.094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856032PMC
February 2021

Early Cognitive Decline and its Impact on Spouse's Loneliness.

Res Hum Dev 2020 1;17(1):78-93. Epub 2020 Jul 1.

Department of Psychology and Statistics, University of Michigan.

Background: Loneliness is common in dementia caregivers as cognitive impairment (CI) alters marital and social relationships. Unexplored is how an individual's loneliness is affected at earlier, more ambiguous, periods of their spouse's CI.

Methods: Using the Health and Retirement Study, our study participants included 2,206 coupled individuals with normal cognitive function at the 2006/8 baseline. Loneliness outcomes at baseline, 4-year and 8-year follow-up are assessed by the status of transition to cognitive impairment no dementia (TCIND) (2010/12 & 2014/16) using linear mixed models.

Results: Individual's loneliness was stable when their spouse's cognition remained normal, but increased with the spouse's TCIND. The increase in loneliness did not vary by gender.

Conclusions: Loneliness, a key risk factor for reduced life quality and increased depression, increases even at early stages of a partner's CIND. This work suggests the potential impact of early intervention and social support for partners of individuals with CIND.
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http://dx.doi.org/10.1080/15427609.2020.1750293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540914PMC
July 2020

Unhealthy alcohol and drug use is associated with an increased length of stay and hospital cost in patients undergoing major upper gastrointestinal and pancreatic oncologic resections.

Surgery 2021 03 18;169(3):636-643. Epub 2020 Sep 18.

Department of Surgery, Loyola University Medical Center, Maywood, IL; Edward Hines, Jr. Veterans Administration Hospital, Hines, IL. Electronic address:

Background: Few studies evaluate the impact of unhealthy alcohol and drug use on the risk and severity of postoperative outcomes after upper gastrointestinal and pancreatic oncologic resections.

Methods: The National Inpatient Sample was queried to identify patients undergoing total gastrectomy, esophagectomy, total pancreatectomy, and pancreaticoduodenectomy between 2012 and 2015. Unhealthy alcohol and drug use was assessed by the International Classification of Diseases, Ninth Revision, and National Inpatient Sample coder designation. Multivariable regression was used to identify associations between alcohol and drug use and postoperative complication, duration of stay, hospital cost, and mortality.

Results: In the study, 59,490 patients met inclusion criteria; 2,060 (3.5%) had unhealthy alcohol use; 1,265 (2.1%) had unhealthy drug use. Postoperative complication rates were higher in patients with alcohol and drug use than in abstainers (67.5% vs 62.8% vs 57.2%; P < .01). On multivariable regression, alcohol use was independently associated with increased risk of a nonwithdrawal complication (odds ratio 1.33 [1.05, 1.68]), and alcohol and drug use were independently associated with increased length of stay (1.54 [0.12, 2.96]) and 2.22 [0.90, 3.55] days) and cost ($5,471 [$60, $10,881] and $4,022 [$402, $7,643]), but not mortality.

Conclusion: Unhealthy substance use is associated with increased rates of postoperative complications, prolonged length of stay, and costs in patients undergoing major upper gastrointestinal and pancreatic oncologic resections. Screening and abstinence interventions should be incorporated into the preoperative care pathways for these patients.
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http://dx.doi.org/10.1016/j.surg.2020.07.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970515PMC
March 2021

Trends, Cost, and Mortality From Sepsis After Trauma in the United States: An Evaluation of the National Inpatient Sample of Hospitalizations, 2012-2016.

Crit Care Med 2020 09;48(9):1296-1303

Department of Health Informatics and Data Science, Loyola University Chicago, Maywood, IL.

Objectives: Identification and outcomes in patients with sepsis have improved over the years, but little data are available in patients with trauma who develop sepsis. We aimed to examine the cost and epidemiology of sepsis in patients hospitalized after trauma.

Design: Retrospective cohort study.

Patients: National Inpatient Sample.

Interventions: Sepsis was identified between 2012 and 2016 using implicit and explicit International Classification of Diseases, Ninth and Tenth Revision codes. Analyses were stratified by injury severity score greater than or equal to 15. Annual trends were modeled using generalized linear models. Survey-adjusted logistic regression was used to compare the odds for in-hospital mortality, and the average marginal effects were calculated to compare the cost of hospitalization with and without sepsis.

Measurements And Main Results: There were 320,450 (SE = 3,642) traumatic injury discharges from U.S. hospitals with sepsis between 2012 and 2016, representing 6.0% (95% CI, 5.9-6.0%) of the total trauma population (n = 5,329,714; SE = 47,447). In-hospital mortality associated with sepsis after trauma did not change over the study period (p > 0.40). In adjusted analysis, severe (injury severity score ≥ 15) and nonsevere injured septic patients had an odds ratio of 1.39 (95% CI, 1.31-1.47) and 4.32 (95% CI, 4.06-4.59) for in-hospital mortality, respectively. The adjusted marginal cost for sepsis compared with nonsepsis was $16,646 (95% CI, $16,294-$16,997), and it was greater than the marginal cost for severe injury compared with nonsevere injury $8,851 (95% CI, $8,366-$8,796).

Conclusions: While national trends for sepsis mortality have improved over the years, our analysis of National Inpatient Sample did not support this trend in the trauma population. The odds risk for death after sepsis and the cost of care remained high regardless of severity of injury. More rigor is needed in tracking sepsis after trauma and evaluating the effectiveness of hospital mandates and policies to improve sepsis care in patients after trauma.
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http://dx.doi.org/10.1097/CCM.0000000000004451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872079PMC
September 2020

Multicenter assessment of the Brain Injury Guidelines and a proposal of guideline modifications.

Trauma Surg Acute Care Open 2020 28;5(1):e000483. Epub 2020 May 28.

Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

Background: The Brain Injury Guidelines provide an algorithm fortreating patients with traumatic brain injury (TBI) and intracranial hemorrhage(ICH) that does not mandate hospital admission, repeat head CT, orneurosurgical consult for all patients. The purposes of this study are toreview the guidelines' safety, to assess resource utilization, and to proposeguideline modifications that improve patient safety and widespreadreproducibility.

Methods: A multi-institutional review of TBI patients was conducted. Patients with ICH on CT were classified as BIG 1, 2, or 3 based on the guidelines. BIG 3 patients were excluded. Variables collected included demographics, Injury Severity Score (ISS), hospital length of stay (LOS), intensive care unit LOS, number of head CTs, type of injury, progression of injury, and neurosurgical interventions performed.

Results: 269 patients met inclusion criteria. 98 were classifiedas BIG 1 and 171 as BIG 2. The median length of stay (LOS) was 2 (2,4)days and the ICU LOS was 1 (0,2) days. Most patients had a neurosurgeryconsultation (95.9%) and all patients included had a repeat head CT. 370repeat head CT scans were performed, representing 1.38 repeat scans perpatient. 11.2% of BIG 1 and 11.1% of BIG 2 patients demonstratedworsening on repeat head CT. Patients who progressed exhibited a higherISS (14 vs. 10, =0.040), and had a longer length of stay (4 vs. 2 days;=0.015). After adjusting for other variables, the presence of epiduralhematoma (EDH) and intraparenchymal hematoma were independent predictors ofprogression. Two BIG 2 patients with EDH had clinical deteriorationrequiring intervention.

Discussion: The Brain Injury Guidelines may improve resourceallocation if utilized, but alterations are required to ensure patientsafety. The modified Brain Injury Guidelines refine the originalguidelines to enhance reproducibility and patient safety while continuing toprovide improved resource utilization in TBI management.
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http://dx.doi.org/10.1136/tsaco-2020-000483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264829PMC
May 2020

Concurrent and enduring associations between married partners' shared beliefs and markers of aging.

Psychol Aging 2020 Nov 11;35(7):925-936. Epub 2020 Jun 11.

Institute for Social Research and Department of Psychology, University of Michigan.

Beliefs about aging are grounded in social experience. This study considered the extent to which married older adults' shared beliefs about aging and markers of aging maintain a concurrent and enduring association with their partners' beliefs about and markers of aging. Data from the 2010/2012 and 2014/2016 waves of the Health and Retirement Study provided measures of husbands' and wives' (3,779 couples) positive and negative beliefs about aging and internal (Cystatin C) and external (grip strength) markers of aging at 2 time points. Latent dyadic models parsed beliefs and markers into partners' individual and shared variances, which were connected both cross-sectionally and longitudinally. Longitudinal analysis showed that the cross-sectional associations between shared beliefs and markers of aging were stable over 4 years. Partners' shared beliefs and markers of aging were found to have enduring associations with each other over time. The enduring association between grip strength and future negative beliefs remained significant after accounting for partner selection and similarity in health. Model comparisons across marriage duration and emotional closeness showed partners' beliefs to be more similar in marriages that were either long established or emotionally close. In all groups, shared beliefs and markers of aging were associated with each other over time. The association between positive beliefs and future grip strength was stronger in long-established than in recent marriages. In summary, this study provides evidence that, within older couples, beliefs about aging are shaped in part through experiences of aging together. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000515DOI Listing
November 2020

Comparison of Common Amplitude Metrics in Event-Related Potential Analysis.

Multivariate Behav Res 2020 May-Jun;55(3):478-493. Epub 2019 Aug 29.

University of Michigan.

Waveform data resulting from time-intensive longitudinal designs require careful treatment. In particular, the statistical properties of summary metrics in this area are crucial. We draw on event-related potential (ERP) studies, a field with a relatively long history of collecting and analyzing such data, to illustrate our points. In particular, three summary measures for a component in the average ERP waveform feature prominently in the literature: the maximum (or peak amplitude), the average (or mean amplitude) and a combination (or adaptive mean). We discuss the methodological divide associated with these summary measures. Through both analytic work and simulation study, we explore the properties (e.g., Type I and Type II errors) of these competing metrics for assessing the amplitude of an ERP component across experimental conditions. The theoretical and simulation-based arguments in this article illustrate how design (e.g., number of trials per condition) and analytic (e.g., window location) choices affect the behavior of these amplitude summary measures in statistical tests and highlight the need for transparency in reporting the analytic steps taken. There is an increased need for analytic tools for waveform data. As new analytic methods are developed to address these time-intensive longitudinal data, careful treatment of the statistical properties of summary metrics used for null hypothesis testing is crucial.
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http://dx.doi.org/10.1080/00273171.2019.1654358DOI Listing
January 2021

Development of externalizing symptoms across the toddler period: The critical role of older siblings.

J Fam Psychol 2020 Mar 12;34(2):165-174. Epub 2019 Aug 12.

Department of Psychology.

We examined child and family risk factors that were associated with the development of individual differences in externalizing problems across the toddler years. Our central hypothesis was that toddlers with more aggressive and disruptive older siblings would be at elevated risk for heightened levels of externalizing behavior. We tested this hypothesis in the context of other theoretically relevant risk factors: toddlers' inhibitory and internalized control, experiences of coercive parental discipline, and gender. Participants were 167 toddlers, their older siblings, and parents in a longitudinal study following younger siblings across the first 3 years of life. Mothers and fathers contributed ratings of externalizing symptoms between 1 and 18 months across the transition to siblinghood for older siblings and 18 to 36 months for younger siblings. Toddlers' inhibitory and internalized control were assessed using behavioral and parent report measures, and parents completed questionnaires concerning their use of coercive discipline. Individual differences in toddler externalizing symptoms were highly stable between 18 and 36 months of age for a sample of second-born children with older siblings, even though there was evidence of significant decline in externalizing symptoms from 18 to 36 months. As predicted, toddlers with elevated levels of externalizing symptoms tended to have older siblings with higher externalizing difficulties across the first 18 months of the younger sibling's life. Thus, these findings highlighted the need for further research on older siblings' contributions to the behavioral development of their toddler-age younger siblings. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012728PMC
March 2020

Clinical Gestalt for Early Prediction of Delayed Functional and Symptomatic Recovery From Mild Traumatic Brain Injury Is Inadequate.

Acad Emerg Med 2019 12 5;26(12):1384-1387. Epub 2019 Sep 5.

Department of Neurology, University of Pennsylvania Perelman School of Medicine, Penn Presbyterian Medical Center, Philadelphia, PA.

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http://dx.doi.org/10.1111/acem.13844DOI Listing
December 2019

Clinical Gestalt for Early Prediction of Delayed Functional and Symptomatic Recovery From Mild Traumatic Brain Injury Is Inadequate.

Acad Emerg Med 2019 12 5;26(12):1384-1387. Epub 2019 Sep 5.

Department of Neurology, University of Pennsylvania Perelman School of Medicine, Penn Presbyterian Medical Center, Philadelphia, PA.

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http://dx.doi.org/10.1111/acem.13844DOI Listing
December 2019

Diminished Value Discrimination in Obsessive-Compulsive Disorder: A Prospect Theory Model of Decision-Making Under Risk.

Front Psychiatry 2019 8;10:469. Epub 2019 Jul 8.

Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.

It has been hypothesized that people diagnosed with anxiety and obsessive-compulsive disorder (OCD) exhibit behavioral aberrations when faced with the potential for negative outcomes, but the specific cognitive aspects of decision-making that may be altered have not been systematically studied in clinical populations. Here, we studied decision-making in a clinical cohort using a task that allows for examination of the decision weights and values associated with different choice outcomes. Patients diagnosed with OCD ( = 10), generalized anxiety disorder ( = 15), social anxiety disorder ( = 14), and healthy controls ( = 20) were given a decision-making task and choices were modeled using a cumulative prospect theory framework. We found OCD patients to have lower value discrimination than controls, as well as less optimal performance on the task, an effect that was mostly driven by trials with only positive outcomes. Our results shed light on the cognitive processes that drive altered decision-making under risk in OCD. Specifically, they demonstrate that OCD patients have diminished sensitivity to positive outcomes, which might be associated with risk aversion and altered learning of gain. These findings also extend prior reports, suggesting that altered cognitive processing during decision-making is linked to altered perception of value, but not probability, in these patients.
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http://dx.doi.org/10.3389/fpsyt.2019.00469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628634PMC
July 2019

Chapter IV: In Search of the Father-Infant Activation Relationship: A Person-Centered Approach.

Monogr Soc Res Child Dev 2019 03 29;84(1):50-63. Epub 2019 Apr 29.

Joint Program in Social Work and Psychology.

The current study explored whether fathers and mothers from 195 two-parent U.S. families engaged in a form of parenting (i.e., sensitivity, cognitive stimulation, and moderate intrusiveness) with their secondborn, 12-month-old infants during a 15-min challenging teaching task, and to determine if this type of interaction was more common among fathers. Mean comparisons showed that fathers were lower on sensitivity, positive regard, and stimulation of development, and were more detached than mothers. Latent Profile Analyses revealed similar , and parenting profile for fathers and mothers, with more fathers in the activation class. Chi-square analyses found significant associations across mothers and fathers; most infants (30%) had activation fathers and mothers, with 26% having supportive mothers and activation fathers, and 11.4% having two supportive parents. Parenting profiles were unrelated to attachment security. Results need to be replicated with children of different ages, with families from different backgrounds, and beyond the challenging teaching paradigm.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625660PMC
March 2019

Is Tracheostomy Insertion an Indication for Gastrostomy Insertion?

Am Surg 2019 May;85(5):518-523

The aim of the study was to determine the frequency of surgical patients who undergo tracheostomy and gastrostomy insertion during the same hospitalization. Secondary outcomes included ICU and hospital length of stay (LOS) for patients who underwent concomitant tracheostomy and gastrostomy those who did not. This study is a retrospective review of trauma and acute care surgery (ACS) patients between 2006 and 2015 who underwent tracheostomy. Patients who also underwent open gastrostomy or percutaneous endoscopic gastrostomy during the same hospitalization were identified. Data collected included patient demographics, hospital LOS, ICU LOS, and timing of tracheostomy and gastrostomy. Three hundred one trauma and ACS patients who underwent tracheostomy were identified. Seventy- three per cent of tracheostomy patients underwent gastrostomy during the same admission. Of patients who had both tubes inserted, 79 per cent (175) underwent gastrostomy with tracheostomy as the concomitant procedure, whereas 21 per cent received gastrostomy as a delayed procedure. Median hospital LOS for patients who underwent concomitant procedures was 25 days 22 days for those who had delayed or no gastrostomy ( = 0.24). Eighty-four per cent of patients who had tracheostomy for prolonged or anticipated prolonged mechanical ventilation were receiving tube feeds at discharge, and 78 per cent had not been advanced to an oral diet at discharge. Most trauma/ACS patients who undergo tracheostomy also undergo gastrostomy during their hospitalization. Concomitant gastrostomy is not associated with a decrease in hospital LOS; however, most patients who undergo tracheostomy for prolonged mechanical ventilation are discharged receiving enteral nutrition. These patients may benefit from concomitant ICU gastrostomy as a way to improve efficiency and cost-saving.
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May 2019

Advancing Research and Measurement on Fathering and Child Development.

Monogr Soc Res Child Dev 2019 03;84(1):7-160

Fathers are more than social accidents. Research has demonstrated that fathers matter to children's development. Despite noted progress, challenges remain on how best to conceptualize and assess fathering and father-child relationships. The current monograph is the result of an SRCD-sponsored meeting of fatherhood scholars brought together to discuss these challenges and make recommendations for best practices for incorporating fathers in studies on parenting and children's development. The first aim of this monograph was to provide a brief update on the current state of research on fathering and to lay out a developmental ecological systems perspective as a conceptual framework for understanding the different spaces fathers inhabit in their children's lives. Because there is wide variability in fathers' roles, the ecological systems perspective situates fathers, mothers, children, and other caregivers within an evolving network of interrelated social relationships in which children and their parents change over time and space (e.g., residence). The second aim was to present examples of empirical studies conducted by members of the international working group that highlighted different methods, data collection, and statistical analyses used to capture the variability in father-child relationships. The monograph ends with a commentary that elaborates on the ecological systems framework with a discussion of the broader macrosystem and social-contextual influences that impinge on fathers and their children. The collection of articles contributes to research on father-child relationships by advancing theory and presenting varied methods and analysis strategies that assist in understanding the father-child relationship and its impact on child development.
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http://dx.doi.org/10.1111/mono.12404DOI Listing
March 2019

Risk factors for infection and evaluation of Sepsis-3 in patients with trauma.

Am J Surg 2019 11 8;218(5):851-857. Epub 2019 Mar 8.

Division of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA.

Background: We aim to examine the risk factors associated with infection in trauma patients and the Sepsis-3 definition.

Methods: This was a retrospective cohort study of adult trauma patients admitted to a Level I trauma center between January 2014 and January 2016.

Results: A total of 1499 trauma patients met inclusion criteria and 15% (n = 232) had an infection. Only 19.8% (n = 46) of infected patients met criteria for Sepsis-3, with the majority (43%) of infected cases having a Sequential Organ Failure Assessment (SOFA) score greater on admission compared to the time of suspected infection. In-hospital death was 7% vs 9% (p = 0.65) between Sepsis-3 and infected patients, respectively. Risk factors associated with infection were female sex, admission SOFA score, Elixhauser score, and severe injury (P < 0.05).

Conclusion: Patients with trauma often arrive with organ dysfunction, which adds complexity and inaccuracy to the operational definition of Sepsis-3 using changes in SOFA scores. Injury severity score, comorbidities, SOFA score, and sex are risk factors associated with developing an infection after trauma.
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http://dx.doi.org/10.1016/j.amjsurg.2019.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732249PMC
November 2019

Performance of bioMérieux Lowenstein-Jensen slopes in plastic tube packaging, compared to existing phenotypic methods, for efficient recovery of the Mycobacterium tuberculosis complex.

J Med Microbiol 2019 Mar 6;68(3):398-401. Epub 2019 Feb 6.

1 Section of Microbiology, Department of Laboratory Medicine, PD Hinduja Hospital and Medical Research Centre, Mumbai, India.

Purpose: Lowenstein-Jensen (LJ) medium used for cultivating Mycobacterium tuberculosis (MTB) is marketed in glass packaging. Breakage of glass slope is a major biosafety risk, especially during processing and storage, which gets magnified in large laboratories. We evaluated the performance of new bioMérieux (bMx) LJ slopes in plastic packaging, compared to bMx glass LJ medium and Becton Dickinson Mycobacterial Growth Indicator Tube (MGIT), for MTB recovery.

Methodology: Consecutive pulmonary/extra-pulmonary samples (n=240) were processed using routine methods of decontamination, inoculation and incubation.

Results: Plastic LJ slopes detected all 213 true-positive cases. The mean time-to-growth detection was 17.97 days for plastic LJ slopes, compared to 18.08 and 13.53 days for glass LJ slopes and MGIT, respectively. No statistically significant difference was observed between the two LJ slopes (P< 0.05). Both LJ slopes had a sensitivity and specificity of 100%, with respect to MGIT.

Conclusion: Plastic LJ slopes are a good alternative to the traditional glass slopes. The medium quality did not differ with the packaging material. Increased surface area of these slants allowed enhanced growth, and the clear plastic material allowed accurate recording of growth. The wide mouth of these containers eased inoculation. Increased biosafety, by elimination of breakage risk, is the biggest advantage of this modification.
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http://dx.doi.org/10.1099/jmm.0.000930DOI Listing
March 2019

Natural language processing and machine learning to identify alcohol misuse from the electronic health record in trauma patients: development and internal validation.

J Am Med Inform Assoc 2019 03;26(3):254-261

Health Sciences Division, Center for Health Outcomes and Informatics Research, Loyola University, Maywood, Illinois, USA.

Objective: Alcohol misuse is present in over a quarter of trauma patients. Information in the clinical notes of the electronic health record of trauma patients may be used for phenotyping tasks with natural language processing (NLP) and supervised machine learning. The objective of this study is to train and validate an NLP classifier for identifying patients with alcohol misuse.

Materials And Methods: An observational cohort of 1422 adult patients admitted to a trauma center between April 2013 and November 2016. Linguistic processing of clinical notes was performed using the clinical Text Analysis and Knowledge Extraction System. The primary analysis was the binary classification of alcohol misuse. The Alcohol Use Disorders Identification Test served as the reference standard.

Results: The data corpus comprised 91 045 electronic health record notes and 16 091 features. In the final machine learning classifier, 16 features were selected from the first 24 hours of notes for identifying alcohol misuse. The classifier's performance in the validation cohort had an area under the receiver-operating characteristic curve of 0.78 (95% confidence interval [CI], 0.72 to 0.85). Sensitivity and specificity were at 56.0% (95% CI, 44.1% to 68.0%) and 88.9% (95% CI, 84.4% to 92.8%). The Hosmer-Lemeshow goodness-of-fit test demonstrates the classifier fits the data well (P = .17). A simpler rule-based keyword approach had a decrease in sensitivity when compared with the NLP classifier from 56.0% to 18.2%.

Conclusions: The NLP classifier has adequate predictive validity for identifying alcohol misuse in trauma centers. External validation is needed before its application to augment screening.
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http://dx.doi.org/10.1093/jamia/ocy166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657384PMC
March 2019

Selection of nonlinear interactions by a forward stepwise algorithm: Application to identifying environmental chemical mixtures affecting health outcomes.

Stat Med 2019 04 26;38(9):1582-1600. Epub 2018 Dec 26.

Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan.

In this paper, we propose a stepwise forward selection algorithm for detecting the effects of a set of correlated exposures and their interactions on a health outcome of interest when the underlying relationship could potentially be nonlinear. Though the proposed method is very general, our application in this paper remains to be on analysis of multiple pollutants and their interactions. Simultaneous exposure to multiple environmental pollutants could affect human health in a multitude of complex ways. For understanding the health effects of multiple environmental exposures, it is often important to identify and estimate complex interactions among exposures. However, this issue becomes analytically challenging in the presence of potential nonlinearity in the outcome-exposure response surface and a set of correlated exposures. Through simulation studies and analyses of test datasets that were simulated as a part of a data challenge in multipollutant modeling organized by the National Institute of Environmental Health Sciences (http://www.niehs.nih.gov/about/events/pastmtg/2015/statistical/), we illustrate the advantages of our proposed method in comparison with existing alternative approaches. A particular strength of our method is that it demonstrates very low false positives across empirical studies. Our method is also used to analyze a dataset that was released from the Health Outcomes and Measurement of the Environment Study as a benchmark beta-tester dataset as a part of the same workshop.
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http://dx.doi.org/10.1002/sim.8059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134269PMC
April 2019

Tests of Matrix Structure for Construct Validation.

Psychometrika 2019 03 27;84(1):65-83. Epub 2018 Nov 27.

University of Michigan, Ann Arbor, MI, USA.

Psychologists and other behavioral scientists are frequently interested in whether a questionnaire measures a latent construct. Attempts to address this issue are referred to as construct validation. We describe and extend nonparametric hypothesis testing procedures to assess matrix structures, which can be used for construct validation. These methods are based on a quadratic assignment framework and can be used either by themselves or to check the robustness of other methods. We investigate the performance of these matrix structure tests through simulations and demonstrate their use by analyzing a big five personality traits questionnaire administered as part of the Health and Retirement Study. We also derive rates of convergence for our overall test to better understand its behavior.
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http://dx.doi.org/10.1007/s11336-018-9647-4DOI Listing
March 2019

Maternal and paternal trajectories of depressive symptoms predict family risk and children's emotional and behavioral problems after the birth of a sibling.

Dev Psychopathol 2019 10;31(4):1307-1324

Center for Human Growth and Development, University of Michigan,Ann Arbor, MI,USA.

The current study examined trajectories of maternal and paternal depression in the year following the birth of an infant sibling, and relations with family risk factors and firstborn children's internalizing and externalizing behavior problems. Latent class growth analysis was conducted on 231 families in a longitudinal investigation (prebirth and 1, 4, 8, and 12 months postbirth) and revealed four classes of families: both mother and father low in depressive symptoms (40.7%); mother high-father low (25.1%); father high-mother low (24.7%), and both mother and father high (9.5%). Families with both mothers and fathers high on depressive symptoms were higher on marital negativity, parenting stress, and children's internalizing and externalizing problems, and lower on marital positivity and parental efficacy than other classes. Children, parents, and marital relationships were more problematic in families with fathers higher on depressive symptoms than in families in which mothers were higher, indicating the significant role of paternal support for firstborn children undergoing the transition to siblinghood. Maternal and paternal depression covaried with an accumulation of family risks over time, no doubt increasing the likelihood of children's problematic adjustment after the birth of their infant sibling.
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http://dx.doi.org/10.1017/S0954579418000743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500778PMC
October 2019

Paths into Sepsis: Trajectories of Presepsis Healthcare Use.

Ann Am Thorac Soc 2019 01;16(1):116-123

1 Department of Internal Medicine and.

Rationale: Sepsis is a leading cause of death and disability whose heterogeneity is often cited as a key impediment to translational progress.

Objectives: To test the hypothesis that there are consequential and significant differences in sepsis outcomes that result from differences in a patient's clinical course leading up to sepsis hospitalization.

Methods: We conducted an observational cohort study of U.S. Health and Retirement Study (HRS) participants in Medicare (1998-2012) and U.S. Department of Veterans Affairs beneficiaries (2009). Using latent profile analysis, we identified patient subtypes based on trajectory of presepsis healthcare facility use. Subtypes were identified in the derivation cohort (1,512 sepsis hospitalizations among earlier HRS participants), then validated them in two additional cohorts (1,992 sepsis hospitalizations among later HRS participants; 32,525 sepsis hospitalizations among U.S. Department of Veterans Affairs beneficiaries). We measured the association between presepsis path and 90-day mortality using chi-square tests and multivariable logistic regression.

Results: We identified three subtypes: low use of inpatient healthcare facilities, comprising 84% of the derivation cohort; rising use, 12%; and high use, 4%. The shape and distribution of presepsis trajectories were similar in all three cohorts. In the derivation cohort, 90-day mortality differed by presepsis trajectory as follows: 38% (low use), 63% (rising use), and 48% (high use) (P < 0.001). This association persisted in the validation cohorts (P < 0.001 for each). The rising use class remained an independent predictor of mortality after adjustment for potential confounders, including detailed physiologic data.

Conclusions: In national cohorts of patients with sepsis, we have shown that several distinct paths into sepsis exist. These paths, identified by trajectories of presepsis healthcare use, are predictive of 90-day mortality.
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http://dx.doi.org/10.1513/AnnalsATS.201806-391OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344453PMC
January 2019