Caffeine and kidney function at two years in former extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. METHODS: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation. PRIMARY OUTCOMES: 'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. RESULTS: 598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). CONCLUSIONS: Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. IMPACT: In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

Aligning the planning, development, and implementation of complex interventions to local contexts with an equity focus: application of the PRISM/RE-AIM Framework.

For the fields of implementation science and health equity, understanding and being responsive to local contexts is of utmost importance to better inform the development, implementation, and evaluation of healthcare and public health interventions to increase their uptake and sustainment. Contexts are multi-level and include political, historical, economic, and social factors that influence health, as well as organizational characteristics, reflecting the richness of members' views, resources, values, and needs. Poor alignment between solutions and those contextual characteristics could have an impact on inequities. The PRISM (Practical Robust Implementation and Sustainability Model) is a context-based implementation science framework that incorporates RE-AIM outcomes (Reach, Effectiveness, Adoption, Implementation, Maintenance) and offers guidance to researchers, practitioners, and their patient and community partners on how to conceptualize, assess, and address contextual domains with a focus on health equity. Drawing from systems thinking, participatory engagement, and health equity principles, this commentary expands on previous work to 1) offer a novel perspective on how to align an intervention's core functions and forms with the PRISM's contextual domains, and 2) foster an ongoing and iterative engagement process with diverse partners throughout the research and practice process using a co-creation approach. We recommend intervention-to-context alignment through iterative cycles. To that end, we present the RE-AIM Framework's 'outcomes cascade' to illustrate touch points of opportunity and gaps within and across each of the five RE-AIM outcomes to illustrate 'where things go wrong'. We present a case study to illustrate and offer recommendations for research and practice efforts to increase contextual responsiveness, and enhance alignment with context before, during, and after implementation efforts and to ensure equity is being addressed. We strive to make a conceptual contribution to advance the field of pragmatic research and implementation of evidence-based practices through the application of the contextually-based PRISM framework with a focus on health equity.

Novel predictors of mortality in emergency bowel surgery: a single-centre cohort study.

Pre-operative risk stratification is a key part of the care pathway for emergency bowel surgery, as it facilitates the identification of high-risk patients. Several novel risk scores have recently been published that are designed to identify patients who are frail or significantly unwell. They can also be calculated pre-operatively from routinely collected clinical data. This study aimed to investigate the ability of these scores to predict 30-day mortality after emergency bowel surgery. A single centre cohort study was performed using our local data from the National Emergency Laparotomy Audit database. Further data were extracted from electronic hospital records (n = 1508). The National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score were then calculated. The most abnormal National or Laboratory Decision Tree Early Warning Score in the 24 or 72 h before surgery was used in analysis. Individual scores were reasonable predictors of mortality (c-statistic 0.699-0.740) but all were poorly calibrated. A National Early Warning Score ≥ 4 was associated with a high overall mortality rate (> 10%). A logistic regression model was developed using age, National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score as predictor variables, and its performance compared with other established risk models. The model demonstrated good discrimination and calibration (c-statistic 0.827) but was marginally outperformed by the National Emergency Laparotomy Audit score (c-statistic 0.861). All other models compared performed less well (c-statistics 0.734-0.808). Pre-operative patient vital signs, blood tests and markers of frailty can be used to accurately predict the risk of 30-day mortality after emergency bowel surgery.

A Multicenter Analysis of the Early Impact of COVID-19 on Junior Resident Operative Case Volume.

INTRODUCTION: Institutions have reported decreases in operative volume due to COVID-19. Junior residents have fewer opportunities for operative experience and COVID-19 further jeopardizes their operative exposure. This study quantifies the impact of the COVID-19 pandemic on resident operative exposure using resident case logs focusing on junior residents and categorizes the response of surgical residency programs to the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective multicenter cohort study was conducted; 276,481 case logs were collected from 407 general surgery residents of 18 participating institutions, spanning 2016-2020. Characteristics of each institution and program changes in response to COVID-19 were collected via surveys. RESULTS: Senior residents performed 117 more cases than junior residents each year (P < 0.001). Prior to the pandemic, senior resident case volume increased each year (38 per year, 95% confidence interval 2.9-74.9) while junior resident case volume remained stagnant (95% confidence interval 13.7-22.0). Early in the COVID-19 pandemic, junior residents reported on average 11% fewer cases when compared to the three prior academic years (P = 0.001). The largest decreases in cases were those with higher resident autonomy (Surgeon Jr, P = 0.03). The greatest impact of COVID-19 on junior resident case volume was in community-based medical centers (246 prepandemic versus 216 during pandemic, P = 0.009) and institutions which reached Stage 3 Program Pandemic Status (P = 0.01). CONCLUSIONS: Residents reported a significant decrease in operative volume during the 2019 academic year, disproportionately impacting junior residents. The long-term consequences of COVID-19 on junior surgical trainee competence and ability to reach cases requirements are yet unknown but are unlikely to be negligible.

Explanatory models of hypertension in Guatemala: recognizing the perspectives of patients, family members, health care providers and administrators, and national-level health system stakeholders.

BACKGROUND: Uncontrolled hypertension is a major public health burden and the most common preventable risk factor for cardiovascular diseases in Guatemala and other low- and middle-income countries. Prior to an initial trial that evaluated a hypertension intervention in rural Guatemala, we collected qualitative information on the needs and knowledge gaps of hypertension care within Guatemala's public healthcare system. This analysis applied Kleinman's Explanatory Models of Illness to capture how patients, family members, community-, district-, and provincial-level health care providers and administrators, and national-level health system stakeholders understand hypertension.  METHODS: We conducted in-depth interviews with three types of participants: 1) national-level health system stakeholders (n = 17), 2) local health providers and administrators from district, and health post levels (25), and 3) patients and family members (19) in the departments of Sololá and Zacapa in Guatemala. All interviews were conducted in Spanish except for 6 Maya-Kaqchikel interviews. We also conducted focus group discussions with auxiliary nurses (3) and patients (3), one in Maya-Tz'utujil and the rest in Spanish. Through framework and matrix analysis, we compared understandings of hypertension by participant type using the Explanatory Model of Illness domains -etiology, symptoms, pathophysiology, course of illness, and treatment. RESULTS: Health providers and administrators, and patients described hypertension as an illness that spurs from emotional states like sadness, anger, and worry; is inherited and related to advanced age; and produces symptoms that include a weakened body, nerves, pain, and headaches. Patients expressed concerns about hypertension treatment's long-term consequences, despite trying to comply with treatment. Patients stated that they combine biomedical treatment (when available) with natural remedies (teas and plants). Health providers and administrators and family members stated that once patients feel better, they often disengage from treatment. National-level health system stakeholders referred to lifestyle factors as important causes, considered patients to typically be non-compliant, and identified budget limitations as a key barrier to hypertension care. The three groups of participants identified structural barriers to limited hypertension care (e.g., limited access to healthy food and unaffordability of medications). CONCLUSION: As understandings of hypertension vary between types of participants, it is important to describe their similarities and differences considering the role each has in the health system. Considering different perceptions of hypertension will enable better informed program planning and implementation efforts.

The Rhesus Macaque Serves As a Model for Human Lateral Branch Nephrogenesis.

BACKGROUND: Most nephrons are added in late gestation. Truncated extrauterine nephrogenesis in premature infants results in fewer nephrons and significantly increased risk for CKD in adulthood. To overcome the ethical and technical difficulties associated with studies of late-gestation human fetal kidney development, third-trimester rhesus macaques served as a model to understand lateral branch nephrogenesis (LBN) at the molecular level. METHODS: Immunostaining and 3D rendering assessed morphology. Single-cell (sc) and single-nucleus (sn) RNA-Seq were performed on four cortically enriched fetal rhesus kidneys of 129-131 days gestational age (GA). An integrative bioinformatics strategy was applied across single-cell modalities, species, and time. RNAScope validation studies were performed on human archival tissue. RESULTS: Third-trimester rhesus kidney undergoes human-like LBN. scRNA-Seq of 23,608 cells revealed 37 transcriptionally distinct cell populations, including naïve nephron progenitor cells (NPCs), with the prior noted marker genes CITED1, MEOX1, and EYA1 (c25). These same populations and markers were reflected in snRNA-Seq of 5972 nuclei. Late-gestation rhesus NPC markers resembled late-gestation murine NPC, whereas early second-trimester human NPC markers aligned to midgestation murine NPCs. New, age-specific rhesus NPCs (SHISA8) and ureteric buds (POU3F4 and TWIST) predicted markers were verified in late-gestation human archival samples. CONCLUSIONS: Rhesus macaque is the first model of bona fide LBN, enabling molecular studies of late gestation, human-like nephrogenesis. These molecular findings support the hypothesis that aging nephron progenitors have a distinct molecular signature and align to their earlier human counterparts, with unique markers highlighting LBN-specific progenitor maturation.

Under-Recognition of Neonatal Acute Kidney Injury and Lack of Follow-Up.

OBJECTIVE: Acute kidney injury (AKI) incidence is 30% in neonatal intensive care units (NICU). AKI is associated with increased mortality and risk of chronic kidney disease (CKD) in children. To assess follow-up and early CKD, we retrospectively reviewed outcomes of Cincinnati Children's Hospital Medical Center (CCHMC) cohort of neonates from the AWAKEN trial (2014). STUDY DESIGN: Data from 81 CCHMC patients were extracted from the AWAKEN dataset. KDIGO (Kidney Disease: Improving Global Outcomes) criteria for serum creatinine (SCr) and urine output (UOP) <1 mL/kg/h, reported per 24 hours on postnatal days 2 to 7, were used to define AKI. Charts were reviewed until May 2019 for death, nephrology consult, AKI diagnosis on discharge summary, follow-up, and early CKD at >6 months of age (defined as: estimated glomerular filtration rate < 90 mL/min/1.73 m2, hyperfiltration, proteinuria, hypertension, or abnormal ultrasound). Patients were considered to have renal follow-up if they had ≥1 follow-up visit containing: SCr, urinalysis, or blood pressure measurement. RESULTS: Seventy-seven patients had sufficient data to ascertain AKI diagnosis. In total 47 of 77 (61%) were AKI+ by SCr or UOP criteria (20 stage 1, 14 stage 2, 13 stage 3). Four died during their admission and five were removed from CKD analyses due to urologic anomalies. AKI-UOP alone outnumbered AKI-SCr (45 AKI+ vs 5 AKI+ for all stages). 33% of patients had <2 SCr measured while inpatient. Only 3 of 47 AKI+ patients had a nephrology consult (all stage 3 by SCr) and 2 of 47 had AKI included in discharge summary. 67% of AKI+ patients had follow-up. In total 10 of 43 (23%) AKI+ versus 12 of 25 (48%) AKI- patients had ≥1 marker of early CKD assessed after 6 months. Based on SCr, 3 of 7 (43%) AKI+ had hyperfiltration versus 0 of 7 (0%) AKI- (p = 0.19). CONCLUSION: AKI is vastly under-recognized in the NICU, especially if based on SCr alone. This leads to insufficient follow-up to ascertain renal sequelae in this high-risk population. KEY POINTS: · AKI is under-recognized in high-risk neonates.. · There is a lack of adequate follow-up.. · Identification of AKI by SCr alone is insufficient..

Interfacial water morphology in hydrated melanin.

The importance of electrically functional biomaterials is increasing as researchers explore ways to utilise them in novel sensing capacities. It has been recognised that for many of these materials the state of hydration is a key parameter that can heavily affect the conductivity, particularly those that rely upon ionic or proton transport as a key mechanism. However, thus far little attention has been paid to the nature of the water morphology in the hydrated state and the concomitant ionic conductivity. Presented here is an inelastic neutron scattering (INS) experiment on hydrated eumelanin, a model bioelectronic material, in order to investigate its 'water morphology'. We develop a rigorous new methodology for performing hydration dependent INS experiments. We also model the eumelanin dry spectra with a minimalist approach whereas for higher hydration levels we are able to obtain difference spectra to extract out the water scattering signal. A key result is that the physi-sorbed water structure within eumelanin is dominated by interfacial water with the number of water layers between 3-5, and no bulk water. We also detect for the first time, the potential signatures for proton cations, most likely the Zundel ion, within a biopolymer/water system. These new signatures may be general for soft proton ionomer systems, if the systems are comprised of only interfacial water within their structure. The nature of the water morphology opens up new questions about the potential ionic charge transport mechanisms within hydrated bioelectronics materials.

Omentectomy reduces the need for peritoneal dialysis catheter revision in children: a study from the Pediatric Nephrology Research Consortium.

BACKGROUND: There are no multi-center studies examining omentectomy and peritoneal dialysis (PD) catheter revision in the pediatric dialysis population. METHODS: We performed a retrospective study at eight centers within the Pediatric Nephrology Research Consortium (PNRC). Data review included all incident tunneled PD catheters placed between 1/1/2011 and 12/31/2016 in pediatric stage 5 chronic kidney disease (CKD 5) patients. The primary outcome was the need for catheter revision and/or replacement. Multivariable logistic regression was performed to evaluate predictors for catheter revision/replacement. RESULTS: Data from 184 children (62.5% male; median age 7.4 years) were analyzed. Omentectomy was completed in 63.6% (n = 117). Revision/replacement occurred in 34.2% (n = 63); median time to revision/replacement was 38.5 days after insertion. PD catheter revision/replacement catheter occurred in 23.9% who underwent omentectomy versus 52.2% without omentectomy (p = 0.0005). Children ≥ 6 years at the time of catheter insertion experienced fewer revisions/replacements (18.2% age ≥ 6 vs. 56.5% age < 6 years, p <0.001). After adjusting for covariates, omentectomy reduced the need for revision by 63%; revision was 3.66 times more likely in those < 6 years of age. CONCLUSIONS: This multi-center study demonstrates that omentectomy at the time of PD catheter insertion in pediatric patients is strongly associated with reduced likelihood of PD catheter revision. Omentectomy should be considered at the time of PD catheter insertion, especially in young children who are at high risk for PD catheter malfunction. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hypertension in Guatemala's Public Primary Care System: A Needs Assessment Using the Health System Building Blocks Framework.

BACKGROUND: Uncontrolled hypertension represents a substantial and growing burden in Guatemala and other low and middle-income countries. As a part of the formative phase of an implementation research study, we conducted a needs assessment to define short- and long-term needs and opportunities for hypertension services within the public health system. METHODS: We conducted a multi-method, multi-level assessment of needs related to hypertension within Guatemala's public system using the World Health Organization's health system building blocks framework. We conducted semi-structured interviews with stakeholders at national (n = 17), departmental (n = 7), district (n = 25), and community (n = 30) levels and focus groups with patients (3) and frontline auxiliary nurses (3). We visited and captured data about infrastructure, accessibility, human resources, reporting, medications and supplies at 124 health posts and 53 health centers in five departments of Guatemala. We conducted a thematic analysis of transcribed interviews and focus group discussions supported by matrix analysis. We summarized quantitative data observed during visits to health posts and centers. RESULTS: Major challenges for hypertension service delivery included: gaps in infrastructure, insufficient staffing and high turnover, limited training, inconsistent supply of medications, lack of reporting, low prioritization of hypertension, and a low level of funding in the public health system overall. Key opportunities included: prior experience caring for patients with chronic conditions, eagerness from providers to learn, and interest from patients to be involved in managing their health. The 5 departments differ in population served per health facility, accessibility, and staffing. All but 7 health posts had basic infrastructure in place. Enalapril was available in 74% of health posts whereas hydrochlorothiazide was available in only 1 of the 124 health posts. With the exception of one department, over 90% of health posts had a blood pressure monitor. CONCLUSIONS: This multi-level multi-method needs assessment using the building blocks framework highlights contextual factors in Guatemala's public health system that have been important in informing the implementation of a hypertension control trial. Long-term needs that are not addressed within the scope of this study will be important to address to enable sustained implementation and scale-up of the hypertension control approach.

Implementation of a Diabetes Self-Management Education and Support Intervention in Rural Guatemala: A Mixed-Methods Evaluation Using the RE-AIM Framework.

INTRODUCTION: To address the global diabetes epidemic, lifestyle counseling on diet, physical activity, and weight loss is essential. This study assessed the implementation of a diabetes self-management education and support (DSMES) intervention using a mixed-methods evaluation framework. METHODS: We implemented a culturally adapted, home-based DSMES intervention in rural Indigenous Maya towns in Guatemala from 2018 through 2020. We used a pretest-posttest design and a mixed-methods evaluation approach guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Quantitative data included baseline characteristics, implementation metrics, effectiveness outcomes, and costs. Qualitative data consisted of semistructured interviews with 3 groups of stakeholders. RESULTS: Of 738 participants screened, 627 participants were enrolled, and 478 participants completed the study. Adjusted mean change in glycated hemoglobin A1c was -0.4% (95% CI, -0.6% to -0.3%; P < .001), change in systolic blood pressure was -5.0 mm Hg (95% CI, -6.4 to -3.7 mm Hg; P < .001), change in diastolic blood pressure was -2.6 mm Hg (95% CI, -3.4 to -1.9 mm Hg; P < .001), and change in body mass index was 0.5 (95% CI, 0.3 to 0.6; P < .001). We observed improvements in diabetes knowledge, distress, and most self-care activities. Key implementation factors included 1) recruitment barriers for men, 2) importance of patient-centered care, 3) role of research staff in catalyzing health worker involvement, 4) tradeoffs between home and telephone visits, and 5) sustainability challenges. CONCLUSION: A community health worker-led DSMES intervention was successfully implemented in the public health system in rural Guatemala and resulted in significant improvements in most clinical and psychometric outcomes. Scaling up sustainable DSMES in health systems in rural settings requires careful consideration of local barriers and facilitators.

Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal Crosstalk.

BACKGROUND: Current management of AKI, a potentially fatal disorder that can also initiate or exacerbate CKD, is merely supportive. Therefore, deeper understanding of the molecular pathways perturbed in AKI is needed to identify targets with potential to lead to improved treatment. METHODS: We performed single-cell RNA sequencing (scRNA-seq) with the clinically relevant unilateral ischemia-reperfusion murine model of AKI at days 1, 2, 4, 7, 11, and 14 after AKI onset. Using real-time quantitative PCR, immunofluorescence, Western blotting, and both chromogenic and single-molecule in situ hybridizations, we validated AKI signatures in multiple experiments. RESULTS: Our findings show the time course of changing gene expression patterns for multiple AKI stages and all renal cell types. We observed elevated expression of crucial injury response factors-including kidney injury molecule-1 (Kim1), lipocalin 2 (Lcn2), and keratin 8 (Krt8)-and of several novel genes (Ahnak, Sh3bgrl3, and Col18a1) not previously examined in kidney pathologies. AKI induced proximal tubule dedifferentiation, with a pronounced nephrogenic signature represented by Sox4 and Cd24a. Moreover, AKI caused the formation of "mixed-identity cells" (expressing markers of different renal cell types) that are normally seen only during early kidney development. The injured tubules acquired a proinflammatory and profibrotic phenotype; moreover, AKI dramatically modified ligand-receptor crosstalk, with potential pathologic epithelial-to-stromal interactions. Advancing age in AKI onset was associated with maladaptive response and kidney fibrosis. CONCLUSIONS: The scRNA-seq, comprehensive, cell-specific profiles provide a valuable resource for examining molecular pathways that are perturbed in AKI. The results fully define AKI-associated dedifferentiation programs, potential pathologic ligand-receptor crosstalk, novel genes, and the improved injury response in younger mice, and highlight potential targets of kidney injury.

Improving Lower Extremity Bypass Patient Outcomes: Enhanced Recovery After Surgery Implementation Project.

BACKGROUND: Care variation is associated with poor quality outcomes. Clinical practice guideline implementation is one method to decrease care variation and improve outcomes. Enhanced Recovery After Surgery (ERAS) is a clinical pathway encompassing best practices across the surgical patient care continuum. LOCAL PROBLEM: The lower extremity bypass (LEB) population had high length of stay (LOS), readmissions, and surgical site infections. METHODS: A comprehensive and systematic project management process was utilized to implement the ERAS pathway in the LEB population with the help of an interdisciplinary team. INTERVENTIONS: Clinical practice guidelines were created to integrate ERAS elements into the LEB population care continuum. Patient education was revised or created to ensure standardized information was communicated to patients from consultation through discharge and early follow-up. RESULTS: Preliminary data show 4.57 mean LOS (n = 21) compared with the prior year's mean of 6.81 (n = 53). CONCLUSION: ERAS pathway introduction to the LEB population is suggestive of improved outcomes based on preliminary data.

Haptoglobin degradation product as a novel serum biomarker for hematopoietic stem cell transplant-associated thrombotic microangiopathy.

BACKGROUND: Hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a well-known complication of HSCT and carries high risk of morbidity and mortality. A lack of consistent non-invasive diagnostic criteria can delay diagnosis and lead to irreversible organ damage. METHODS: Serum samples of 100 patients that underwent HSCT at Cincinnati Children's Hospital were serially collected. Unbiased proteomic profiling by SELDI-TOF-MS was performed on serum from TA-TMA patients at baseline (pre-HSCT), 2 weeks before TMA diagnosis (pre-TMA), and at clinical TMA diagnosis. Two proteins with mass to charge ratios of 12-13 kDa were consistently elevated at the 2 week pre-TMA time point by SELDI-TOF, compared to control samples. Potential peptides were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the Linear Trap Quadropole (LTQ). A MASCOT search identified haptoglobin fragments in the 12-17-kDa range. Western blot was performed to validate haptoglobin fragments as a potential biomarker. RESULTS: Western blot of TA-TMA patients showed haptoglobin fragments at 12, 14, and 17 kDa that varied between baseline, pre-TMA, and TMA time points for each patient. By densitometric analysis, the 17-kDa fragment in the pre-TMA samples differed significantly from TMA diagnosis (p < 0.0001). There was no significant difference in the concentrations of the 12-kDa and 14-kDa fragments. CONCLUSION: The 17-kDa haptoglobin degradation product may represent a novel early serum biomarker for TA-TMA that could potentially allow for earlier diagnosis and intervention.

2018 John N. Insall Award: Recovery of Knee Flexion With Unsupervised Home Exercise Is Not Inferior to Outpatient Physical Therapy After TKA: A Randomized Trial.

BACKGROUND: Concerns about the cost and convenience of postsurgical physical therapy (PT) have sparked interest in unsupervised, home-based rehabilitation. However, the effectiveness of unsupervised home exercise after primary TKA has not been previously evaluated. QUESTIONS/PURPOSES: (1) Can unsupervised home exercise after surgery provide noninferior recovery of passive knee flexion compared with formal outpatient PT? (2) Does a web-based platform for home-based exercise provide an advantage compared with a printed PT manual? METHODS: We conducted a randomized, noninferiority trial involving 290 patients (20% of the 1464 eligible patients who could be contacted) who underwent primary TKA from March 2016 to April 2018. We included patients > 18 years old who were undergoing primary, unilateral TKA and provided written consent. We excluded patients with preoperative knee flexion < 90°, patients considering surgical intervention in a hip or the contralateral knee, patients discharged to an extended care facility, and revision or conversion TKA. We randomized patients to one of three groups: outpatient PT, unsupervised home exercise using a web-based platform (web PT), or unsupervised home exercise using a printed paper manual (paper PT). We also implemented a "delayed recovery intervention" within the home exercise program, in which patients were obliged to begin outpatient PT if knee flexion was < 70° at 2 weeks or < 90° at 4 weeks. The primary outcome was change in knee flexion from preoperative baseline after 4 to 6 weeks and 6 months. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), time back to activities of daily living, and time off narcotics. All analyses were intention to treat, and the noninferiority margin was 5% with maximum flexion as the outcome of interest for this parameter. RESULTS: Adjusted differences in change in passive flexion for web PT +3° (95% confidence interval [CI], -1.2° to 6.4°) and paper PT +5° (95% CI, 0.99°-8.6°) were not inferior to outpatient PT based on a predefined 5° margin. Change in knee flexion from baseline was 0° for outpatient PT, -2° for web PT, and -1° for paper PT after 4 to 6 weeks and 8°, 8°, and 12° for the three groups, respectively, after 6 months. Additionally, there was no difference in the change in KOOS from baseline at 4 to 6 weeks or 6 months postoperatively as well as time back to work, driving, and walking without an assistive device. CONCLUSIONS: Unsupervised home exercise is an effective rehabilitation strategy after primary TKA and was noninferior to formal outpatient PT in selected patients. It is worthwhile to reconsider the current practice of automatically designating patients for outpatient PT after primary TKA, because appropriately selected patients with adequate clinical support can achieve similar results at home. LEVEL OF EVIDENCE: Level I, therapeutic study.

Cardioembolic Stroke Risk and Recovery After Anticoagulation-Related Intracerebral Hemorrhage.

Background and Purpose- Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods- We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHA2DS2-VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results- In multivariable analyses, the CHA2DS2-VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79-0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHA2DS2-VASc score (odds ratio, 1.89; 95% CI, 1.32-2.70). We found an interaction between CHA2DS2-VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P=0.011). Conclusions- Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.

Neural and behavioral effects of regulating emotional responses to errors during an implicit racial bias task.

Affect regulation plays a key role in several theories of racial bias reduction. Here, we tested whether engaging in emotion regulation strategies while performing an implicit racial bias task (Weapons Identification Task; WIT) would alter neural and behavioral manifestations of bias. Participants either suppressed or reappraised in a positive light the distress associated with making errors during the WIT, while an electroencephalogram (EEG) was recorded. We hypothesized that engaging in emotion regulation strategies would reduce the distress associated with making errors indicative of bias, resulting in smaller error-related negativity (ERN) amplitude during errors and increased expression of racial bias. Results of within-subjects comparisons (Experiment 1) generally supported these predictions. However, when emotion regulation strategies were manipulated between subjects (Experiment 2) there was no effect of suppression or reappraisal on bias expression. Across both experiments, engaging in emotion regulation led to larger ERNs for errors occurring on Black- relative to White-primed trials. In addition, a number of significant order effects were observed, indicating important differences in the effects of engaging in emotion regulation strategies when those strategies are attempted in participants' first versus second block of trials. No such order effects were evident when a second trial block was completed with no emotion regulation instructions. Findings are discussed in terms of the need for greater specificity in experimental tests of emotion regulation on error processing and cognitive performance.

University-Affiliated Alcohol Marketing Enhances the Incentive Salience of Alcohol Cues.

We tested whether affiliating beer brands with universities enhances the incentive salience of those brands for underage drinkers. In Study 1, 128 undergraduates viewed beer cues while event-related potentials (ERPs) were recorded. Results showed that beer cues paired with in-group backgrounds (logos for students' universities) evoked an enhanced P3 ERP component, a neural index of incentive salience. This effect varied according to students' levels of identification with their university, and the amplitude of the P3 response prospectively predicted alcohol use over 1 month. In Study 2 ( N = 104), we used a naturalistic advertisement exposure to experimentally create in-group brand associations and found that this manipulation caused an increase in the incentive salience of the beer brand. These data provide the first evidence that marketing beer via affiliating it with students' universities enhances the incentive salience of the brand for underage students and that this effect has implications for their alcohol involvement.

Impact of enhanced recovery after surgery (ERAS) protocol on gastrointestinal function in gynecologic oncology patients undergoing laparotomy.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients. METHODS: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation. The primary outcome was rate of postoperative ileus, defined as nausea and vomiting requiring nothing-per-mouth status or nasogastric tube (NGT) placement. Secondary outcomes included length of stay (LOS) and 30-day readmission. RESULTS: 376 patients met inclusion criteria; 197 in the control group and 179 in the ERAS group. Patient demographics were similar between groups. Ileus rate was significantly lower in the ERAS group (2.8% vs. 15.7%; p < 0.001), and fewer patients in the ERAS group required NGT placement (2.2% vs. 7.1%; p = 0.06). ERAS remained independently associated with decreased ileus rates when controlling for other patient and surgical factors (OR 0.2; p = 0.01). Epidural use was correlated with a significant increase in ileus risk (OR 2.6; p = 0.03), as was increased Charlson Comorbidity Index (OR 1.2; p < 0.01). LOS was significantly decreased in the ERAS group (2.9 vs. 4.0 days; p = 0.04), while 30-day readmission rates were similar (10.1% vs. 10.7%; p = 0.62). CONCLUSIONS: Implementation of an ERAS protocol significantly decreases the risk of postoperative ileus in gynecologic oncology patients undergoing laparotomy. ERAS also reduced LOS compared to pre-ERAS controls.