Coaching to Bedside Shift Report and Its Correlation to Hospital Consumer Assessment of Healthcare Providers and Systems and Value-Based Purchasing Dimension Scores: A Multihospital Implementation Study.

OBJECTIVE: The objective of this multihospital study was to investigate how the intervention of coaching to bedside shift report (BSR) correlates with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) outcomes and relates to Centers for Medicare and Medicaid Services (CMS) Hospital Value-Based Purchasing (VBP) Program points over a 4-year period (2017-2020) for an acute care hospital health system. BACKGROUND: Hospital leaders' responsibilities include intertwined areas of patient experience and fiscal accountability. Coaching to BSR is reported to have numerous benefits to the patient's experience. Published studies completed with hospital systems evaluating the intervention of coaching to BSR and how it correlated to patient experience and VBP are limited. METHODS: Coaching to BSR was implemented at 16 adult acute care hospitals. Patient-reported BSR rates were collected in tandem with HCAHPS for 4 years. Statistical correlations were assessed between patient-reported BSR and HCAHPS and consequential effect on VBP dimension scores. RESULTS: Coaching to BSR had a significant impact on top- and bottom-box "rate the hospital" HCAHPS scores at a system and hospital level. Value-based purchasing points and percentages increased over 2017-2020, potentially leading to lower CMS penalty claims over the period the BSR was implemented. CONCLUSIONS: Coaching is a key factor when creating a favorable patient experience. The implementation and sustainability of coaching to BSR may result in improved patient experience ratings and increase VBP point accumulation to hospital systems.

Path Analysis of the Mediating Roles of Personality, Distress, and Cognitive Flexibility in the Subjective Well-Being of Combat Veterans With Traumatic Brain Injury.

OBJECTIVE: To determine the interrelationships among traumatic brain injury (TBI), maladaptive personality traits (MPT), psychological distress, and cognitive flexibility in the prediction of subjective well-being of post-9/11 veterans concurrently and over time. SETTING: Five Veterans Affairs (VA) medical centers and 1 VA outpatient clinic in urban, suburban, and rural areas. PARTICIPANTS: Five hundred Operation Enduring Freedom/Operation Iraqi Freedom veterans at baseline (219 with TBI), 292 at 18-month follow-up (108 with TBI), drawn from a regional registry and clinic referrals. DESIGN: Path analysis of data from a prospective cohort study. MAIN MEASURES: Satisfaction with Life Scale, 36-ltem Short-Form Health Survey (SF-36) Health Scale, Personality Assessment Screener, Beck Depression Inventory-II, Beck Anxiety Inventory, Posttraumatic Stress Disorder Checklist-Military, Trail Making Test, Part B, Delis-Kaplan Executive Function System (D-KEFS) Category-Switching Verbal Fluency, and D-KEFS Color-Word Interference Test. RESULTS: There was no direct effect of TBI on well-being at baseline or 18 months later. Psychological distress, MPT, and cognitive flexibility had significant direct effects on well-being at baseline and 18 months. Baseline model accounted for 66% of the variance in well-being; follow-up model accounted for 43% of well-being variance. Negative influence of distress significantly decreased from baseline to follow-up. Direct negative effect of MPT diminished slightly over 18 months; effect of cognitive flexibility increased. Significant relationships were estimated in prediction of distress by MPT, cognitive flexibility, and TBI. TBI predicted MPT. MPT, cognitive flexibility, and TBI had indirect effects on well-being. TBI had a positive indirect influence on distress. Total effects included 4 significant predictors of well-being at baseline and 18 months: distress, MPT, cognitive flexibility, and TBI. CONCLUSION: Experience of TBI alone did not predict subjective well-being at baseline or 18 months later. Psychological distress, MPT, and cognitive flexibility had direct effects on well-being at both time points. Interventions aimed at reducing distress and bolstering resilience and cognitive flexibility are recommended to increase subjective well-being in this population.

RCT of a Comprehensive Outpatient Treatment for Children with Autism Spectrum Disorder.

Objective: This study tested the efficacy of an intensive outpatient psychosocial treatment for children with autism spectrum disorder (ASD) without intellectual disability (ID).Method: Eighty-eight children (ages 7-12 years) were randomly assigned to the treatment or control (waitlist) condition. The 18-week cognitive-behavioral treatment (two 90-min sessions per week) included small-group instruction and therapeutic activities targeting social/social-communication skills, face-emotion recognition, nonliteral language skills, and interest expansion. A behavioral system was used to increase skills development and reduce ASD symptoms. Efficacy was tested immediately following treatment (posttest), with maintenance assessed 4-6 weeks later (follow-up). Measures included parent ratings of the children's social/social-communication skills, ASD symptoms, broad social skills, and behavior symptoms, child tests of social-cognitive skills (emotion recognition and nonliteral language), and behavioral observations.Results:Significant effects favoring the treatment group were found at posttest on the primary measures of ASD symptoms (Social Responsiveness Scale, Second Edition; Constantino & Gruber, 2012) and social/social-communication skills (Adapted Skillstreaming Checklist; Lopata, Thomeer, Volker, Nida & Lee, 2008), and secondary measures of nonliteral language skills, broad social skills, and behavior symptoms (measures of emotion-recognition skills and social behaviors during structured game sessions were non-significant). The significant treatment effects found at posttest were all maintained at follow-up.Conclusions: The outpatient treatment improved several core areas of functioning for children with ASD without ID. Additional elements may be needed to expand the efficacy of the treatment so that the observed skills/symptom improvements generalize to social interactions during gameplay.

Community Effectiveness RCT of a Comprehensive Psychosocial Treatment for High-Functioning Children With ASD.

This community effectiveness randomized clinical trial examined the feasibility and effectiveness of a comprehensive psychosocial treatment, summerMAX, when implemented by a community agency. Fifty-seven high-functioning children (48 male, 9 female), ages 7-12 years with autism spectrum disorder participated in this study. The 5-week summerMAX treatment included instruction and therapeutic activities targeting social/social-communication skills, interpretation of nonliteral language skills, face-emotion recognition skills, and interest expansion. A behavioral program was also used to increase skills acquisition and decrease autism spectrum disorder symptoms and problem behaviors. Feasibility was supported via high levels of fidelity and parent, child, and staff clinician satisfaction. Significant treatment effects favoring the treatment group over waitlist controls were found on all 5 of the primary outcome measures (i.e., child test of nonliteral language skills and parent ratings of the children's autism spectrum disorder symptoms, targeted social/social-communication skills, broader social performance, and withdrawal). Staff clinician ratings substantiated the improvements reported by parents. Results of this randomized clinical trial are consistent with those of prior studies of summerMAX and suggest that the program was feasible and effective when implemented by a community agency under real-world conditions.

Cluster Randomized Trial of a School Intervention for Children with Autism Spectrum Disorder.

There are currently no empirically supported, comprehensive school-based interventions (CSBIs) for children with autism spectrum disorder (ASD) without concomitant intellectual and language disability. This study compared outcomes for a CSBI (schoolMAX) to typical educational programming (services-as-usual [SAU]) for these children. A total of 103 children (6-12 years of age) with ASD (without intellectual and language disability) were randomly assigned by school buildings (clusters) to receive the CSBI (n = 52 completed) or SAU (n = 50 completed). The CSBI was implemented by trained school personnel and targeted social competence and ASD symptoms using social skills groups, emotion recognition instruction, therapeutic activities, behavioral reinforcement, and parent training. Outcome measures tested the effects of the CSBI on social competence and ASD symptoms, as well as potential collateral effects on academic achievement. Outcomes (baseline-to-follow-up) were assessed using tests of social cognition and academic skills and behavioral observations (by masked evaluators) and parent-teacher ratings of ASD symptoms and social/social-communication skills (nonmasked; ClinicalTrials.gov, NCT03338530, https://www.clinicaltrials.gov/). The CSBI group improved significantly more than the SAU group on the test of emotion recognition skills and parent-teacher ratings of ASD symptoms (primary outcomes) and social/social-communication skills (secondary outcome). No differences between groups were detected for recess social interactions or academic skills. The CSBI improved several core areas of functioning for children with ASD compared to usual educational programming. Additional intervention elements may be needed to expand the efficacy of the CSBI so that the observed skills/symptom improvements generalize to recess social interactions and/or academic skills are enhanced.

A Nursing Leadership Immersion Program: Succession Planning Using Social Capital.

This article describes the inception and evolution of a 3-month immersion experience between hospital and nurse leaders where sociological principles were applied to support nurse leader succession. Unique to this program, the bedside nurse joins the nursing executive team full time to participate in all organizational leadership activities as part of the experience.

Impaired practice effects following mild traumatic brain injury: an event-related potential investigation.

BACKGROUND: The negative effects of mild traumatic brain injury (mTBI) on attention are well established. Effects of practice on neuropsychological test performance have also been long recognized and more recently linked to electrophysiological indices of information processing. OBJECTIVE: The current study examined the behavioural and electrophysiological impact of mTBI on consistent practice of a neuropsychological test of attention. RESEARCH DESIGN: Prospective cohort study. METHODS: Adult participants with a history of mild TBI (n = 10; time since injury > 2 months, mean = 15.2 months) and healthy matched controls (n = 10) completed the Paced Auditory Serial Addition Task (PASAT) at four separate sessions. Event-related potentials (ERPs) were simultaneously recorded. RESULTS: Accuracy of PASAT performance in both groups improved significantly with practice. In healthy controls behavioural improvements were associated with significant attenuation of a frontally distributed ERP component marker of executive attention. These executive attention demands did not appear to ease with consistent practice in the mTBI group, who also endorsed more concussion-related symptoms. CONCLUSIONS: These preliminary results suggest sustained mental effort is required to achieve 'normal' performance levels following mTBI and support the use of practice-related, ERP indices of recovery from mTBI as a sensitive correlate of persistent post-concussion symptoms.

Meaning-centered dream work with hospice patients: A pilot study.

OBJECTIVE: Hospice patients often struggle with loss of meaning, while many experience meaningful dreams. The purpose of this study was to conduct a preliminary exploration into the process and therapeutic outcomes of meaning-centered dream work with hospice patients. METHOD: A meaning-centered variation of the cognitive-experiential model of dream work (Hill, 1996; 2004) was tested with participants. This variation was influenced by the tenets of meaning-centered psychotherapy (Breitbart et al., 2012). A total of 12 dream-work sessions were conducted with 7 hospice patients (5 women), and session transcripts were analyzed using the consensual qualitative research (CQR) method (Hill, 2012). Participants also completed measures of gains from dream interpretation in terms of existential well-being and quality of life. RESULTS: Participants' dreams generally featured familiar settings and living family and friends. Reported images from dreams were usually connected to feelings, relationships, and the concerns of waking life. Participants typically interpreted their dreams as meaning that they needed to change their way of thinking, address legacy concerns, or complete unfinished business. Generally, participants developed and implemented action plans based on these interpretations, despite their physical limitations. Participants described dream-work sessions as meaningful, comforting, and helpful. High scores on a measure of gains from dream interpretation were reported, consistent with qualitative findings. No adverse effects were reported or indicated by assessments. SIGNIFICANCE OF RESULTS: Our results provided initial support for the feasibility and helpfulness of dream work in this population. Implications for counseling with the dying and directions for future research were also explored.

Physics-informed neural networks as surrogate models of hydrodynamic simulators.

In response to growing concerns surrounding the relationship between climate change and escalating flood risk, there is an increasing urgency to develop precise and rapid flood prediction models. Although high-resolution flood simulations have made notable advancements, they remain computationally expensive, underscoring the need for efficient machine learning surrogate models. As a result of sparse empirical observation and expensive data collection, there is a growing need for the models to perform effectively in 'small-data' contexts, a characteristic typical of many scientific problems. This research combines the latest developments in surrogate modelling and physics-informed machine learning to propose a novel Physics-Informed Neural Network-based surrogate model for hydrodynamic simulators governed by Shallow Water Equations. The proposed method incorporates physics-based prior information into the neural network structure by encoding the conservation of mass into the model without relying on calculating continuous derivatives in the loss function. The method is demonstrated for a high-resolution inland flood simulation model and a large-scale regional tidal model. The proposed method outperforms the existing state-of-the-art data-driven approaches by up to 25 %. This research demonstrates the benefits and robustness of physics-informed approaches in surrogate modelling for flood and hydroclimatic modelling problems.

Longitudinal Follow-Up Study of Social Intervention Outcomes for Children on the Autism Spectrum.

A prior randomized trial found a school social intervention yielded significantly better outcomes (social and autism features) immediately following intervention compared to typical school programming (services-as-usual [SAU]) for children on the autism spectrum. In that study, children in the SAU condition subsequently completed a summer social intervention. This study tested longer-term maintenance of effects for children who completed both interventions. A total of 103 children (ages 6-12 years) on the autism spectrum enrolled and 102 completed the initial RCT. Following the summer social intervention, 90 children from the original RCT completed the longer-term follow-up study. In addition to baseline and posttest in the initial RCT, children from both groups were tested at three follow-up points (five total testing points). At the time of first longitudinal follow-up testing, the children were 1.25-4.25 years post-intervention (ages 8-15 years). Longitudinal multilevel model analyses (and follow-up contrasts) revealed significant improvements for both groups post-intervention on measures of emotion recognition, autism features, and social skills, indicating maintenance of post-intervention improvements over the three follow-up testing points. No between-group differences were found for autism features or social skills over time; however, the school social intervention may have yielded somewhat better emotion recognition skills. Exploratory tests found that child IQ, language level, and length of time since completing the intervention did not moderate outcomes. Both social interventions yielded positive and durable longer-term improvements for children on the autism spectrum. [ClinicalTrials.gov, NCT03338530; November 8, 2017; original retrospectively registered trial].

Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Aerobic exercise attenuates abnormal myelination and oligodendrocyte differentiation in 3xTg-AD mice.

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination.

Preparing for the next pandemic: lessons learnt from the implementation of point-of-care SARS-CoV-2 testing in an emergency department.

Point-of-care testing (POCT) provides rapid, accurate results that facilitate diagnosis and patient management. POCT for infectious agents allows timely infection prevention and control interventions and informs decisions around safe patient placement. However, POCT implementation requires careful governance as they are primarily operated by staff with limited prior education on laboratory quality control and assurance processes. Here, we describe our experience implementing SARS-CoV-2 POCT in the emergency department of a large tertiary referral hospital during the COVID-19 pandemic. We describe collaborative governance between pathology and clinical specialities, quality assurance, testing (volume and positivity rates), impact on patient flow and focus on lessons learnt during implementation that should be incorporated into revised pandemic preparedness planning.

Natural infection versus hybrid (natural and vaccination) humoral immune response to SARS-CoV-2: a comparative paired analysis.

Objectives: There is substantial immunological evidence that vaccination following natural infection increases protection. We compare the humoral immune response developed in initially seropositive individuals (naturally infected) to humoral hybrid immune response (developed after infection and vaccination) in the same population group after one year. Methods: The study included 197 male individuals who were naturally infected with SARS-CoV-2 and then vaccinated with SARS-CoV-2 vaccine. Trimeric spike, nucleocapsid, and ACE2-RBD blocking antibodies for SARS-CoV-2 were measured. Nasal swabs were collected for SARS-CoV-2 PCR testing. Information on vaccination against SARS-CoV-2 and PCR verified infection was retrieved from official databases (Abu Dhabi Health Data Services- SP LLC. ("Malaffi"), including number of vaccine doses received, date of vaccination, and type of the received vaccine. Results: All the study population were tested PCR-Negative at the time of sample collection. Our results showed that there was a significant rise in the mean (SD) and median (IQR) titers of trimeric spike, nucleocapsid and ACE2-RBD blocking antibodies in the post-vaccination stage. The mean (± SD) and median (IQR) concentration of the anti-S antibody rose by 3.3-fold (+230% ± 197% SD) and 2.8-fold (+185%, 220-390%, p<0.001), respectively. There was an observed positive dose-response relationship between number of the received vaccine doses and having higher proportion of study participants with higher than median concentration in the difference between the measured anti-S and ACE2-RBD blocking antibodies in the post-vaccination compared to pre-vaccination. Conclusion: Our study demonstrates that COVID-19 vaccination post natural infection elicits a robust immunological response with an impressive rise of SARS-CoV-2 antibodies, especially the ACE2-RBD blocking antibodies.

Susceptibility to reinfection with SARS-CoV-2 virus relative to existing antibody concentrations and T cell response.

OBJECTIVES: We investigated the reinfection rate of vaccinated or convalescent immunized SARS-CoV-2 in 952 expatriate workers with SARS-CoV-2 serological antibody (Ab) patterns and surrogate T cell memory at recruitment and follow-up. METHODS: Trimeric spike, nucleocapsid, and neutralizing Abs were measured, along with a T cell stimulation assay, targeting SARS-CoV-2 memory in clusters of differentiation (CD) 4+ and CD8+ T cells. The subjects were then followed up for reinfection for up to 6 months. RESULTS: The seroprevalence positivity at enrollment was greater than 99%. The T cell reactivity in this population was 38.2%. Of the 149 (15.9%) participants that were reinfected during the follow-up period (74.3%) had nonreactive T cells at enrollment. Those who had greater than 100 binding Ab units/ml increase from the median concentration of antispike immunoglobulin G Abs had a 6% reduction in the risk of infection. Those who were below the median concentration had a 78% greater risk of infection. CONCLUSION: Significant immune protection from reinfection was observed in those who retained T cell activation memory. Additional protection was observed when the antispike was greater than the median value.

Prosaccade errors in the antisaccade task: differences between corrected and uncorrected errors and links to neuropsychological tests.

The relations among spatial memory, Stroop-like colour-word subtests, and errors on antisaccade and memory-guided saccadic eye-movement trials for older and younger adults were tested. Two types of errors in the antisaccade task were identified: short latency prosaccade errors that were immediately corrected and longer latency uncorrected prosaccade errors. The age groups did not differ on percentages of either corrected or uncorrected errors, but the latency and time to correct prosaccade errors were shorter for younger than older adults. Uncorrected prosaccade errors correlated significantly with spatial memory accuracy and errors on the colour-word subtests, but neither of these neuropsychological indices correlated with corrected prosaccade errors. These findings suggest that uncorrected prosaccade errors may be a result of cognitive factors involving a failure to maintain the goal of the antisaccade task in working memory. In contrast, corrected errors may be a consequence of a fixation system involving an initial failure to inhibit a reflexive prosaccade but with active goal maintenance enabling correction to take place.

Gaussian process emulation of spatio-temporal outputs of a 2D inland flood model.

The computational limitations of complex numerical models have led to adoption of statistical emulators across a variety of problems in science and engineering disciplines to circumvent the high computational costs associated with numerical simulations. In flood modelling, many hydraulic and hydrodynamic numerical models, especially when operating at high spatiotemporal resolutions, have prohibitively high computational costs for tasks requiring the instantaneous generation of very large numbers of simulation results. This study examines the appropriateness and robustness of Gaussian Process (GP) models to emulate the results from a hydraulic inundation model. The developed GPs produce real-time predictions based on the simulation output from LISFLOOD-FP numerical model. An efficient dimensionality reduction scheme is developed to tackle the high dimensionality of the output space and is combined with the GPs to investigate the predictive performance of the proposed emulator for estimation of the inundation depth. The developed GP-based framework is capable of robust and straightforward quantification of the uncertainty associated with the predictions, without requiring additional model evaluations and simulations. Further, this study explores the computational advantages of using a GP-based emulator over alternative methodologies such as neural networks, by undertaking a comparative analysis. For the case study data presented in this paper, the GP model was found to accurately reproduce water depths and inundation extent by classification and produce computational speedups of approximately 10,000 times compared with the original simulator, and 80 times for a neural network-based emulator.

Effect of COVID-19 Stay-at-Home Restrictions on Parent Reported Symptom Severity and Adaptive Functioning of Youth with ASD.

This study assessed the potential short-term effects of COVID-19 stay-at-home restrictions on ratings of ASD and comorbid symptoms severity and adaptive functioning of 69 youth, ages 8-16 years with ASD without intellectual disability. Parent/caregiver ratings were being collected in fall and spring over approximately two years when the restrictions were imposed four months prior to the final data collection point. Results indicated no significant changes in parent/caregiver ratings of ASD symptom severity, comorbid symptoms severity, social skills, or adaptive behaviors following the stay-at-home restrictions and little variability across the four data collection points. Although findings suggested minimal short-term effects on these symptoms and adaptive skills, ongoing monitoring is needed to assess longer-term impacts.

Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response.

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.

Modulation of ERCC1-XPF Heterodimerization Inhibition via Structural Modification of Small Molecule Inhibitor Side-Chains.

Inhibition of DNA repair enzymes is an attractive target for increasing the efficacy of DNA damaging chemotherapies. The ERCC1-XPF heterodimer is a key endonuclease in numerous single and double strand break repair processes, and inhibition of the heterodimerization has previously been shown to sensitize cancer cells to DNA damage. In this work, the previously reported ERCC1-XPF inhibitor 4 was used as the starting point for an in silico study of further modifications of the piperazine side-chain. A selection of the best scoring hits from the in silico screen were synthesized using a late stage functionalization strategy which should allow for further iterations of this class of inhibitors to be readily synthesized. Of the synthesized compounds, compound 6 performed the best in the in vitro fluorescence based endonuclease assay. The success of compound 6 in inhibiting ERCC1-XPF endonuclease activity in vitro translated well to cell-based assays investigating the inhibition of nucleotide excision repair and disruption of heterodimerization. Subsequently compound 6 was shown to sensitize HCT-116 cancer cells to treatment with UVC, cyclophosphamide, and ionizing radiation. This work serves as an important step towards the synergistic use of DNA repair inhibitors with chemotherapeutic drugs.