Improving transitions and outcomes of sepsis survivors (I-TRANSFER): a type 1 hybrid protocol.

BACKGROUND: This protocol is based on home health care (HHC) best practice evidence showing the value of coupling timely post-acute care visits by registered nurses and early outpatient provider follow-up for sepsis survivors. We found that 30-day rehospitalization rates were 7 percentage points lower (a 41% relative reduction) when sepsis survivors received a HHC nursing visit within 2 days of hospital discharge, at least 1 more nursing visit the first week, and an outpatient provider follow-up visit within 7 days compared to those without timely follow-up. However, nationwide, only 28% of sepsis survivors who transitioned to HHC received this timely visit protocol. The opportunity exists for many more sepsis survivors to benefit from timely home care and outpatient services. This protocol aims to achieve this goal.  METHODS: Guided by the Consolidated Framework for Implementation Research, this Type 1 hybrid pragmatic study will test the effectiveness of the Improving Transitions and Outcomes of Sepsis Survivors (I-TRANSFER) intervention compared to usual care on 30-day rehospitalization and emergency department use among sepsis survivors receiving HHC. The study design includes a baseline period with no intervention, a six-month start-up period followed by a one-year intervention period in partnership with five dyads of acute and HHC sites. In addition to the usual care/control periods from the dyad sites, additional survivors from national data will serve as control observations for comparison, weighted to produce covariate balance. The hypotheses will be tested using generalized mixed models with covariates guided by the Andersen Behavioral Model of Health Services. We will produce insights and generalizable knowledge regarding the context, processes, strategies, and determinants of I-TRANSFER implementation. DISCUSSION: As the largest HHC study of its kind and the first to transform this novel evidence through implementation science, this study has the potential to produce new knowledge about the impact of timely attention in HHC to alleviate symptoms and support sepsis survivor's recovery at home. If effective, the impact of this intervention could be widespread, improving the quality of life and health outcomes for a growing, vulnerable population of sepsis survivors. A national advisory group will assist with widespread results dissemination.

Identifying Barriers to Post-Acute Care Referral and Characterizing Negative Patient Preferences Among Hospitalized Older Adults Using Natural Language Processing.

Our objective was to detect common barriers to post-acute care (B2PAC) among hospitalized older adults using natural language processing (NLP) of clinical notes from patients discharged home when a clinical decision support system recommended post-acute care. We annotated B2PAC sentences from discharge planning notes and developed an NLP classifier to identify the highest-value B2PAC class (negative patient preferences). Thirteen machine learning models were compared with Amazon's AutoGluon deep learning model. The study included 594 acute care notes from 100 patient encounters (1156 sentences contained 11 B2PAC) in a large academic health system. The most frequent and modifiable B2PAC class was negative patient preferences (18.3%). The best supervised model was Extreme Gradient Boosting (F1: 0.859), but the deep learning model performed better (F1: 0.916). Alerting clinicians of negative patient preferences early in the hospitalization can prompt interventions such as patient education to ensure patients receive the right level of care and avoid negative outcomes.

Examination of five- and four-subtest short form IQ estimations for the Wechsler Intelligence Scale for Children-Fifth edition (WISC-V) in a mixed clinical sample.

Evaluating general cognitive ability (i.e., intelligence) is common in neuropsychological practice, and identifying abbreviated assessments of intelligence is often advantageous. Despite the Wechsler Intelligence Scale for Children, Fifth Edition's (WISC-V) widespread contemporary use, limited research has identified clinically useful short form (SF) full scale IQ (FSIQ) estimations in clinical samples. This study sought to address this gap in the literature. Two hundred sixty-eight pediatric participants (M age = 9.79; 69% male; 88% Caucasian/White) who underwent psychological/neuropsychological evaluation were included. Mean scores for WISC-V scores fell in the low average-to-average ranges, consistent with the clinical nature of this sample (e.g., M FSIQ = 85.3). Ten unique SF combinations with five (pentad) and four (tetrad) subtests, each intentionally selected to represent a breadth of domains subsumed by WISC-V FSIQ, were described by summing subtest age-corrected scaled scores. Regression-based and prorated FSIQ estimates were calculated, and mean differences suggested some prorated estimates should be arithmetically adjusted. Both regression-based and prorated/adjusted methods provided FSIQ estimates that were accurate within five Standard Score points of true FSIQ for approximately 81-92% (pentad) and 65-76% (tetrads) of participants. Prorated/adjusted estimates appeared to provide somewhat better accuracy than regression-based estimates. Relationships between SFs and true FSIQ did not appear to be moderated by participant age, gender, nor how many WISC-V subtests were administered to participants within this archival sample (i.e., 7 vs. 10). Implications of these findings, including benefits, detriments, and other considerations of each SF combination, in addition to limitations of this study, are discussed in detail.

The dimensionality of the Behavior Rating Inventory of Executive Function, Second Edition in a clinical sample.

The parent-report Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) is a widely used pediatric neuropsychological measure. Unfortunately, despite meaningful changes from its predecessor, few studies have examined its internal factor structure (now with Behavioral Regulation [BRI], Emotion Regulation [ERI], and Cognitive Regulation [CRI]), and no available literature has investigated higher order models for the BRIEF-2. This study sought to address this shortcoming in the literature by investigating and reporting on the dimensionality of the parent-report BRIEF-2 in a clinical sample. Two hundred and two (202) pediatric neuropsychology examinees (M age = 9.90; 68% males) with complete data for the parent-report BRIEF-2 were included. Descriptive results revealed generally elevated scores across BRIEF-2 scales (Global Executive Composite M T = 70.16). Exploratory factor analyses suggested two factors (CRI and BRI/ERI) should be extracted, and that higher order models should be considered. Confirmatory factor analyses suggested that a direct hierarchical/bifactor two-factor structure (which was more parsimonious than the theoretical three-factor model) provided the best fit, with a bulk of the variance explained by the general GEC factor. The BRIEF-2 may be best interpreted at the overall level, with relatively less weight given to the index variables, particularly within clinical samples with high levels of reported executive functioning difficulties. Implications of these findings, limitations of the present study, and appropriate directions for future inquiry were discussed.

Systematic review of prediction models for postacute care destination decision-making.

OBJECTIVE: This article reports a systematic review of studies containing development and validation of models predicting postacute care destination after adult inpatient hospitalization, summarizes clinical populations and variables, evaluates model performance, assesses risk of bias and applicability, and makes recommendations to reduce bias in future models. MATERIALS AND METHODS: A systematic literature review was conducted following PRISMA guidelines and the Cochrane Prognosis Methods Group criteria. Online databases were searched in June 2020 to identify all published studies in this area. Data were extracted based on the CHARMS checklist, and studies were evaluated based on predictor variables, validation, performance in validation, risk of bias, and applicability using the Prediction Model Risk of Bias Assessment Tool (PROBAST) tool. RESULTS: The final sample contained 28 articles with 35 models for evaluation. Models focused on surgical (22), medical (5), or both (8) populations. Eighteen models were internally validated, 10 were externally validated, and 7 models underwent both types. Model performance varied within and across populations. Most models used retrospective data, the median number of predictors was 8.5, and most models demonstrated risk of bias. DISCUSSION AND CONCLUSION: Prediction modeling studies for postacute care destinations are becoming more prolific in the literature, but model development and validation strategies are inconsistent, and performance is variable. Most models are developed using regression, but machine learning methods are increasing in frequency. Future studies should ensure the rigorous variable selection and follow TRIPOD guidelines. Only 14% of the models have been tested or implemented beyond original studies, so translation into practice requires further investigation.

Human Factors Considerations in Transitions in Care Clinical Decision Support System Implementation Studies.

Objective: Review transitions in care clinical decision support system (CDSS) implementation studies and describe human factors considerations in users, design, alert types, intervention timing, and implementation outcomes. Methods: Literature review in PubMed guided by subject matter experts. Results: Twelve articles were included. Targeted users included physicians, nurses, pharmacists, or interdisciplinary teams. Alerts were deployed via email, cloud-based software, or the EHR in inpatient and/or outpatient settings. Outcome measures varied across articles, with mixed performance. There were six readmissions-focused, two prescribing, one laboratory, two prescribing and laboratory, and one discharge disposition CDSS. Few articles reported statistically significant differences in outcomes, and many reported alert fatigue. Discussion and Conclusion: Despite the increasing prevalence of CDSS for transitions in care, few articles describe implementation processes and outcomes, and evidence of clinical practice improvement is mixed. Future studies should utilize implementation science frameworks and incorporate appropriate implementation outcomes in addition to traditional clinical outcomes like readmission rates.

Global Repair Profile of Human Alkyladenine DNA Glycosylase on Nucleosomes Reveals DNA Packaging Effects.

Alkyladenine DNA glycosylase (AAG) is the only known human glycosylase capable of excising alkylated purines from DNA, including the highly mutagenic 1,N6-ethenoadenine (εA) lesion. Here, we examine the ability of AAG to excise εA from a nucleosome core particle (NCP), which is the primary repeating unit of DNA packaging in eukaryotes. Using chemical synthesis techniques, we assembled a global population of NCPs in which A is replaced with εA. While each NCP contains no more than one εA lesion, the total population contains εA in 49 distinct geometric positions. Using this global εA-containing NCP system, we obtained kinetic parameters of AAG throughout the NCP architecture. We observed monophasic reaction kinetics across the NCP, but varying amounts of AAG excision. AAG activity is correlated with solution accessibility and local histone architecture. Notably, we identified some highly solution-accessible lesions that are not repaired well, and an increase in repair within the region of asymmetric unwrapping of the nucleosomal DNA end. These observations support in vivo work and provide molecular-level insight into the relationship between repair and NCP architecture.

Initiating base excision repair in chromatin.

The base excision repair (BER) pathway removes modified nucleobases that can be deleterious to an organism. BER is initiated by a glycosylase, which finds and removes these modified nucleobases. Most of the characterization of glycosylase activity has been conducted in the context of DNA oligomer substrates. However, DNA within eukaryotic organisms exists in a packaged environment with the basic unit of organization being the nucleosome core particle (NCP). The NCP is a complex substrate for repair in which a variety of factors can influence glycosylase activity. In this Review, we focus on the geometric positioning of modified nucleobases in an NCP and the consequences on glycosylase activity and initiating BER.

Human OGG1 activity in nucleosomes is facilitated by transient unwrapping of DNA and is influenced by the local histone environment.

If unrepaired, damage to genomic DNA can cause mutations and/or be cytotoxic. Single base lesions are repaired via the base excision repair (BER) pathway. The first step in BER is the recognition and removal of the nucleobase lesion by a glycosylase enzyme. For example, human oxoguanine glycosylase 1 (hOGG1) is responsible for removal of the prototypic oxidatively damaged nucleobase, 8-oxo-7,8-dihydroguanine (8-oxoG). To date, most studies of glycosylases have used free duplex DNA substrates. However, cellular DNA is packaged as repeating nucleosome units, with 145 base pair segments of DNA wrapped around histone protein octamers. Previous studies revealed inhibition of hOGG1 at the nucleosome dyad axis and in the absence of chromatin remodelers. In this study, we reveal that even in the absence of chromatin remodelers or external cofactors, hOGG1 can initiate BER at positions off the dyad axis and that this activity is facilitated by spontaneous and transient unwrapping of DNA from the histones. Additionally, we find that solution accessibility as determined by hydroxyl radical footprinting is not fully predictive of glycosylase activity and that histone tails can suppress hOGG1 activity. We therefore suggest that local nuances in the nucleosome environment and histone-DNA interactions can impact glycosylase activity.

Effects of ionic liquids on the survival, movement, and feeding behavior of the freshwater snail, Physa acuta.

Room-temperature ionic liquids (ILs) are being promoted as environmentally friendly alternatives to volatile organic solvents currently used by industry. Because ILs are novel and not yet in widespread use, their potential impact on aquatic organisms is unclear. We studied the effects of several ILs on the survivorship and behavior (movement and feeding rates) of the freshwater pulmonate snail, Physa acuta. Median lethal concentrations (LC50s) of ILs with imidazolium- and pyridinium-based cations and Br- and PF6- as anions ranged from 1 to 325 mg/L. Toxicity was greatest for ILs with eight-carbon alkyl chains attached to both imidazolium and pyridinium rings and declined with shorter alkyl chains, indicating a positive relationship between alkyl chain length and toxicity. Compared to controls, snails moved more slowly when exposed to butyl- and hexyl-cation ILs at 1 to 3% of LC50 concentrations but were not affected at higher IL concentrations (4-10% of LC50), which is characteristic of U-shaped dose-response curves. Snail movement was not affected by ILs with octyl alkyl groups. Grazing patterns, however, indicated that snails grazed less at higher IL concentrations. Physa acuta egestion rates were reduced in the presence of ILs at 3 to 10% of LC50 concentrations. Thus, nonlethal IL concentrations affected P. acuta behaviors, potentially impacting individual fitness and food web interactions. These results provide initial information needed to assess the potential hazards of ILs should they reach freshwater ecosystems.