Health inequalities in cardiopulmonary resuscitation and use of automated electrical defibrillators in out-of-hospital cardiac arrest.

Out of hospital cardiac arrest (OHCA) outcomes can be improved by strengthening the chain of survival, namely prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED). However, provision of bystander CPR and AED use remains low due to individual patient factors ranging from lack of education to socioeconomic barriers and due to lack of resources such as limited availability of AEDs in the community. Although the impact of health inequalities on survival from OHCA is documented, it is imperative that we identify and implement strategies to improve public health and outcomes from OHCA overall but with a simultaneous emphasis on making care more equitable. Disparities in CPR delivery and AED use in OHCA exist based on factors including sex, education level, socioeconomic status, race and ethnicity, all of which we discuss in this review. Most importantly, we discuss the barriers to AED use, and strategies on how these may be overcome.

Moral distress among intensive care unit professions in the UK: a mixed-methods study.

OBJECTIVE: To assess the experience of moral distress among intensive care unit (ICU) professionals in the UK. DESIGN: Mixed methods: validated quantitative measure of moral distress followed by purposive sample of respondents who underwent semistructured interviews. SETTING: Four ICUs of varying sizes and specialty facilities. PARTICIPANTS: Healthcare professionals working in ICU. RESULTS: 227 questionnaires were returned and 15 interviews performed. Moral distress occurred across all ICUs and professional demographics. It was most commonly related to providing care perceived as futile or against the patient's wishes/interests, followed by resource constraints compromising care. Moral distress score was independently influenced by profession (p=0.02) (nurses 117.0 vs doctors 78.0). A lack of agency was central to moral distress and its negative experience could lead to withdrawal from engaging with patients/families. One-third indicated their intention to leave their current post due to moral distress and this was greater among nurses than doctors (37.0% vs 15.0%). Moral distress was independently associated with an intention to leave their current post (p<0.0001) and a previous post (p=0.001). Participants described a range of individualised coping strategies tailored to the situations faced. The most common and highly valued strategies were informal and relied on working within a supportive environment along with a close-knit team, although participants acknowledged there was a role for structured and formalised intervention. CONCLUSIONS: Moral distress is widespread among UK ICU professionals and can have an important negative impact on patient care, professional wellbeing and staff retention, a particularly concerning finding as this study was performed prior to the COVID-19 pandemic. Moral distress due to resource-related issues is more severe than comparable studies in North America. Interventions to support professionals should recognise the individualistic nature of coping with moral distress. The value of close-knit teams and supportive environments has implications for how intensive care services are organised.

Investigating the impact of brief training in decision-making on treatment escalation to intensive care using objective structured clinical examination-style scenarios.

Background: The decision to admit patients to the intensive care unit (ICU) is complex. Structuring the decision-making process may be beneficial to patients and decision-makers alike. The aim of this study was to investigate the feasibility and impact of a brief training intervention on ICU treatment escalation decisions using the Warwick model- a structured decision-making framework for treatment escalation decisions. Methods: Treatment escalation decisions were assessed using Objective Structured Clinical Examination-style scenarios. Participants were ICU and anaesthetic registrars with experience of making ICU admission decisions. Participants completed one scenario, followed by training with the decision-making framework and subsequently a second scenario. Decision-making data was collected using checklists, note entries and post-scenario questionnaires. Results: Twelve participants were enrolled. Brief decision-making training was successfully delivered during the normal ICU working day. Following training participants demonstrated greater evidence of balancing the burdens and benefits of treatment escalation. On visual analogue scales of 0-10, participants felt better trained to make treatment escalation decisions (4.9 vs 6.8, p = 0.017) and felt their decision-making was more structured (4.7 vs 8.1, p = 0.017).Overall, participants provided positive feedback and reported feeling more prepared for the task of making treatment escalation decisions. Conclusion: Our findings suggest that a brief training intervention is a feasible way to improve the decision-making process by improving decision-making structure, reasoning and documentation. Training was implemented successfully, acceptable to participants and participants were able to apply their learning. Further studies of regional and national cohorts are needed to determine if training benefit is sustained and generalisable.

Small-Molecule Inhibitors of the MLL1 CXXC Domain, an Epigenetic Reader of DNA Methylation.

The CXXC domain is a reader of DNA methylation which preferentially binds to unmethylated CpG DNA motifs. Chromosomal translocations involving the MLL1 gene produce in-frame fusion proteins in which the N-terminal portion of the MLL1 protein harboring its CXXC domain is fused to the C-terminal portion of multiple partners. For the MLL-AF9 fusion, mutations which disrupt CXXC domain-DNA binding abrogate the ability to cause leukemia in mice. Based on this, we initiated an effort to develop small-molecule inhibitors of the MLL1 CXXC domain as a novel approach to therapy. We developed a fluorescence polarization-based assay for MLL CXXC domain-DNA binding and screened a library of Cys-reactive molecules. For the most potent hit from this screen, we have synthesized a library of analogs to explore the structure-activity relationship, defined the binding site using chemical shift perturbations in NMR spectra, and explored the selectivity of compounds across the CXXC domain family.

Intensive care unit visiting and family communication during the COVID-19 pandemic: A UK survey.

Background: Frequent visiting and communication with patients' families are embedded within normal ICU practice, however the COVID-19 pandemic has challenged this, and it is unclear how ICUs are managing. We aimed to investigate how NHS ICUs are approaching family communications and visiting during the COVID-19 pandemic. Methods: An electronic snapshot survey was delivered between 16th April and 4th May 2020 and was open to NHS ICUs. Replies from 134 individual ICUs with COVID patients were included. Results: All reported that visiting was more restricted than normal with 29 (22%) not allowing any visitors, 71 (53%) allowing visitors at the end of a patient's life (EOL) only, and 30 (22%) allowing visitors for vulnerable patients or EOL. Nearly all (n = 130, 97%) were updating families daily, with most initiating the update (n = 120, 92%). Daily telephone calls were routinely made by the medical (n = 75, 55%) or nursing team (n = 50, 37%). Video calling was used by 63 (47%), and 39 (29%) ICUs had developed a dedicated family communication team. Resuscitation and EOL discussions were most frequently via telephone (n = 129, 96%), with 24 (18%) having used video calling, and 15 (11%) reporting discussions had occurred in person. Clinicians expressed their dissatisfaction with the situation and raised concerns about the detrimental effect on patients, families, and staff. Conclusions: COVID-19 has resulted in significant changes across NHS ICUs in how they interact with families. Many units are adapting and moving toward distant and technology-assisted communication. Despite innovative solutions, challenges remain and there may be a role for local and national guidance.

Health inequities in out-of-hospital cardiac arrest.

PURPOSE OF REVIEW: Out-of-hospital cardiac arrest (OHCA) is a time-critical emergency in which a rapid response following the chain of survival is crucial to save life. Disparities in care can occur at each link in this pathway and hence produce health inequities. This review summarises the health inequities that exist for OHCA patients and suggests how they may be addressed. RECENT FINDINGS: There is international evidence that the incidence of OHCA is increased with increasing deprivation and in ethnic minorities. These groups have lower rates of bystander CPR and bystander-initiated defibrillation, which may be due to barriers in accessing cardiopulmonary resuscitation training, provision of public access defibrillators, and language barriers with emergency call handlers. There are also disparities in the ambulance response and in-hospital care following resuscitation. These disadvantaged communities have poorer survival following OHCA. SUMMARY: OHCA disproportionately affects deprived communities and ethnic minorities. These groups experience disparities in care throughout the chain of survival and this appears to translate into poorer outcomes. Addressing these inequities will require coordinated action that engages with disadvantaged communities.

Evaluation of elderly specific pre-hospital trauma triage criteria: a systematic review.

BACKGROUND: Pre-hospital identification of major trauma in elderly patients is key for delivery of optimal care, however triage of this group is challenging. Elderly-specific triage criteria may be valuable. This systematic review aimed to summarise the published pre-hospital elderly-specific trauma triage tools and evaluate their sensitivity and specificity and associated clinical outcomes. METHODS: MEDLINE and EMBASE databases were searched using predetermined criteria (PROSPERO: CRD42019140879). Two authors independently assessed search results, performed data extraction, risk of bias and quality assessments following the Grading of Recommendations, Assessment, Development and Evaluation system. RESULTS: 801 articles were screened and 11 studies met eligibility criteria, including 1,332,300 patients from exclusively USA populations. There were eight unique elderly-specific triage criteria reported. Most studies retrospectively applied criteria to trauma databases, with few reporting real-world application. The Ohio Geriatric Triage Criteria was reported in three studies. Age cut-off ranged from 55 to 70 years with ≥ 65 most frequently reported. All reported existing adult criteria with modified physiological parameters using higher thresholds for systolic blood pressure and Glasgow coma scale, although the values used varied. Three criteria added co-morbidity or anti-coagulant/anti-platelet use considerations. Modifications to anatomical or mechanism of injury factors were used by only one triage criteria. Criteria sensitivity ranged from 44 to 93%, with a median of 86.3%, whilst specificity was generally poor (median 54%). Scant real-world data showed an increase in patients meeting triage criteria, but minimal changes to patient transport destination and mortality. All studies were at risk of bias and assessed of "very low" or "low" quality. CONCLUSIONS: There are several published elderly-specific pre-hospital trauma triage tools in clinical practice, all developed and employed in the USA. Consensus exists for higher thresholds for physiological parameters, however there was variability in age-cut offs, triage criteria content, and tool sensitivity and specificity. Although sensitivity was improved over corresponding 'adult' criteria, specificity remained poor. There is a paucity of published real-world data examining the effect on patient care and clinical outcomes of elderly-specific triage criteria. There is uncertainty over the optimal elderly triage tool and further study is required to better inform practice and improve patient outcomes.

Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

For this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.

Oxygenation strategies prior to and during prehospital emergency anaesthesia in UK HEMS practice (PREOXY survey).

BACKGROUND: Maintaining effective oxygenation throughout the process of Pre-Hospital Emergency Anaesthesia (PHEA) is critical. There are multiple strategies available to clinicians to oxygenate patients both prior to and during PHEA. The optimal pre-oxygenation technique remains unclear, and it is unknown what techniques are being used by United Kingdom Helicopter Emergency Medical Services (HEMS). This study aimed to determine the current pre- and peri-PHEA oxygenation strategies used by UK HEMS services. METHODS: An electronic questionnaire survey was delivered to all UK HEMS services between 05 July and 26 December 2019. Questions investigated service standard operating procedures (SOPs) and individual clinician practice regarding oxygenation strategies prior to airway instrumentation (pre-oxygenation) and oxygenation strategies during airway instrumentation (apnoeic oxygenation). Service SOPs were obtained to corroborate questionnaire replies. RESULTS: Replies were received from all UK HEMS services (n = 21) and 40 individual clinicians. All services specified oxygenation strategies within their PHEA/RSI SOP and most referred to pre-oxygenation as mandatory (81%), whilst apnoeic oxygenation was mandatory in eight (38%) SOPs. The most commonly identified pre-oxygenation strategies were bag-valve-mask without PEEP (95%), non-rebreathable face mask (81%), and nasal cannula at high flow (81%). Seven (33%) services used Mapleson C circuits, whilst there were eight services (38%) that did not carry bag-valve-masks with PEEP valve nor Mapleson C circuits. All clinicians frequently used pre-oxygenation, however there was variability in clinician use of apnoeic oxygenation by nasal cannula. Nearly all clinicians (95%) reported manually ventilating patients during the apnoeic phase, with over half (58%) stating this was their routine practice. Differences in clinician pre-hospital and in-hospital practice related to availability of humidified high flow nasal oxygenation and Mapleson C circuits. CONCLUSIONS: Pre-oxygenation is universal amongst UK HEMS services and is most frequently delivered by bag-valve-mask without PEEP or non-rebreathable face masks, whereas apnoeic oxygenation by nasal cannula is highly variable. Multiple services carry Mapleson C circuits, however many services are unable to deliver PEEP due to the equipment they carry. Clinicians are regularly manually ventilating patients during the apnoeic phase of PHEA. The identified variability in clinical practice may indicate uncertainty and further research is warranted to assess the impact of different strategies on clinical outcomes.

Structure of the Complex of an Iminopyridinedione Protein Tyrosine Phosphatase 4A3 Phosphatase Inhibitor with Human Serum Albumin.

Protein tyrosine phosphatase (PTP) 4A3 is frequently overexpressed in human solid tumors and hematologic malignancies and is associated with tumor cell invasion, metastasis, and a poor patient prognosis. Several potent, selective, and allosteric small molecule inhibitors of PTP4A3 were recently identified. A lead compound in the series, JMS-053 (7-imino-2-phenylthieno[3,2-c]pyridine-4,6(5H,7H)-dione), has a long plasma half-life (∼ 24 hours) in mice, suggesting possible binding to serum components. We confirmed by isothermal titration calorimetry that JMS-053 binds to human serum albumin. A single JMS-053 binding site was identified by X-ray crystallography in human serum albumin at drug site 3, which is also known as subdomain IB. The binding of JMS-053 to human serum albumin, however, did not markedly alter the overall albumin structure. In the presence of serum albumin, the potency of JMS-053 as an in vitro inhibitor of PTP4A3 and human A2780 ovarian cancer cell growth was reduced. The reversible binding of JMS-053 to serum albumin may serve to increase JMS-053's plasma half-life and thus extend the delivery of the compound to tumors. SIGNIFICANCE STATEMENT: X-ray crystallography revealed that a potent, reversible, first-in-class small molecule inhibitor of the oncogenic phosphatase protein tyrosine phosphatase 4A3 binds to at least one site on human serum albumin, which is likely to extend the compound's plasma half-life and thus assist in drug delivery into tumors.

BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity.

MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population.

Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: A systematic review and meta-analysis.

BACKGROUND: Whole blood is optimal for resuscitation of traumatic hemorrhage. Walking Blood Banks provide fresh whole blood (FWB) where conventional blood components or stored, tested whole blood are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the coronavirus disease 2019 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice. METHODS: Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported whole blood from conventional blood banking were excluded. For outcomes, odds ratios (ORs) and 95% confidence interval (CI) were calculated using random-effects modeling because of high risk of heterogeneity. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. RESULTS: Twenty-seven studies published from 2006 to 2020 reported >10,000 U of FWB for >3,000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study, which was "moderate" in quality. Fresh whole blood patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for eight studies that compared these (OR, 1.00 [95% CI, 0.65-1.55]; p = 0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI, 0.13-0.58) for mortality for the FWB group (p < 0.01). CONCLUSION: Thousands of units of FWB from Walking Blood Banks have been transfused in patients following life-threatening hemorrhage. Survival is equivalent for FWB resuscitation when compared with non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas Walking Blood Banks may be an attractive resilience measure, caution is still advised. Walking Blood Banks should be subject to prospective evaluation to optimize care and inform policy. LEVEL OF EVIDENCE: Systematic/therapeutic, level 3.

Emergency front of neck airway: What do trainers in the UK teach? A national survey.

BACKGROUND AND AIMS: Front of neck airway (FONA) is the final step to deliver oxygen in the difficult airway management algorithms. The Difficult Airway Society 2015 guidelines have recommended a standardized scalpel cricothyroidotomy technique for an emergency FONA. There is a wide variability in the FONA techniques with disparate approaches and training. We conducted a national postal survey to evaluate current teaching, availability of equipment, experienced surgical help and prevalent attitudes in the face of a can't intubate, can't oxygenate situation. MATERIAL AND METHODS: The postal survey was addressed to airway leads across National Health Service hospitals in the United Kingdom (UK). In the anesthetic departments with no designated airway leads, the survey was addressed to the respective college tutors. A total of 259 survey questionnaires were posted. RESULTS: We received 209 survey replies with an overall response rate of 81%. Although 75% of respondents preferred scalpel cricothyroidotomy, only 28% of the anesthetic departments considered in-house FONA training as mandatory for all grades of anesthetists. Scalpel-bougie-tube kits were available in 95% of the anesthetic departments, either solely or in combination with other FONA devices. CONCLUSION: The survey has demonstrated that a majority of the airway trainers in the UK would prefer scalpel cricothyroidotomy as emergency FONA. There is a significant variation and deficiency in the current levels of FONA training. Hence, it is important that emergency FONA training is standardized and imparted at a multidisciplinary level.

Advanced airway training in the UK: A national survey of senior anesthetic trainees.

BACKGROUND AND AIMS: High-quality training in advanced airway skills is imperative to ensure safe anesthetic care and develop future airway specialists. Modern airway management skills are continually evolving in response to advancing technology and developing research. Therefore, it is of concern that training provisions and trainee competencies remain current and effective. MATERIAL AND METHODS: A survey questionnaire based on the airway competencies described in the Royal College of Anaesthetists' curriculum and Difficult Airway Society guidelines was posted to all United Kingdom (UK) National Health Service hospitals to be completed by the most senior anesthetic trainee (ST 5-7, resident). RESULTS: A total of 149 responses were analyzed from 237 hospitals with eligible anesthetic trainees (response rate 63%), including 53 (36%) and 39 (26%) respondents who had completed higher and advanced level airway training respectively. Although clinical experience with videolaryngoscopy was satisfactory, poor confidence and familiarity was identified with awake fiberoptic intubation, high frequency jet ventilation, at risk extubation techniques, and airway ultrasound assessment. Only 26 (17%) respondents had access to an airway skills room or had regular airway emergency training with multidisciplinary theater team participation. Reported barriers to training included lack of training lists, dedicated teaching time, experienced trainers, and availability of equipment. CONCLUSIONS: This national survey identified numerous deficiencies in airway competencies and training amongst senior anesthetic trainees (residents) in the UK. Restructuring of the airway training program and improvements in access to training facilities are essential to ensure effective airway training and the capability to produce future airway specialists.

The use of triclosan-coated sutures to prevent surgical site infections: a systematic review and meta-analysis of the literature.

INTRODUCTION AND OBJECTIVES: Surgical site infections (SSIs) represent a common and serious complication of all surgical interventions. Microorganisms are able to colonise sutures that are implanted in the skin, which is a causative factor of SSIs. Triclosan-coated sutures are antibacterial sutures aimed at reducing SSIs. Our objective is to update the existing literature by systematically reviewing available evidence to assess the effectiveness of triclosan-coated sutures in the prevention of SSIs. METHODS: A systematic review of EMBASE, MEDLINE, AMED (Allied and complementary medicine database) and CENTRAL was performed to identify full text randomised controlled trials (RCTs) on 31 May 2019. INTERVENTION: Triclosan-coated sutures versus non-triclosan-coated sutures. PRIMARY OUTCOME: Our primary outcome was the development of SSIs at 30 days postoperatively. A meta-analysis was performed using a fixed-effects model. RESULTS: Twenty-five RCTs were included involving 11 957 participants. Triclosan-coated sutures were used in 6008 participants and non triclosan-coated sutures were used in 5949. Triclosan-coated sutures significantly reduced the risk of SSIs at 30 days (relative risk 0.73, 95% CI 0.65 to 0.82). Further sensitivity analysis demonstrated that triclosan-coated sutures significantly reduced the risk of SSIs in both clean and contaminated surgery. CONCLUSION: Triclosan-coated sutures have been shown to significantly reduced the risk of SSIs when compared with standard sutures. This is in agreement with previous work in this area. This study represented the largest review to date in this area. This moderate quality evidence recommends the use of triclosan-coated sutures in order to reduce the risk of SSIs particularly in clean and contaminated surgical procedures. PROSPERO REGISTRATION NUMBER: CRD42014014856.

Prehospital haemostatic dressings for trauma: a systematic review.

BACKGROUND: Haemorrhage is a major cause of mortality and morbidity following both military and civilian trauma. Haemostatic dressings may offer effective haemorrhage control as part of prehospital treatment. AIM: To conduct a systematic review of the clinical literature to assess the prehospital use of haemostatic dressings in controlling traumatic haemorrhage, and determine whether any haemostatic dressings are clinically superior. METHODS: MEDLINE and EMBASE databases were searched using predetermined criteria. The reference lists of all returned review articles were screened for eligible studies. Two authors independently undertook the search, performed data extraction, and risk of bias and Grading of Recommendations, Assessment, Development and Evaluation quality assessments. Meta-analysis could not be undertaken due to study and clinical heterogeneity. RESULTS: Our search yielded 470 studies, of which 17 met eligibility criteria, and included 809 patients (469 military and 340 civilian). There were 15 observational studies, 1 case report and 1 randomised controlled trial. Indications for prehospital haemostatic dressing use, wound location, mechanism of injury, and source of bleeding were variable. Seven different haemostatic dressings were reported with QuikClot Combat Gauze being the most frequently applied (420 applications). Cessation of bleeding ranged from 67% to 100%, with a median of 90.5%. Adverse events were only reported with QuikClot granules, resulting in burns. No adverse events were reported with QuikClot Combat Gauze use in three studies. Seven of the 17 studies did not report safety data. All studies were at risk of bias and assessed of 'very low' to 'moderate' quality. CONCLUSIONS: Haemostatic dressings offer effective prehospital treatment for traumatic haemorrhage. QuikClot Combat Gauze may be justified as the optimal agent due to the volume of clinical data and its safety profile, but there is a lack of high-quality clinical evidence, and randomised controlled trials are warranted. LEVEL OF EVIDENCE: Systematic review, level IV.

Small molecule inhibition of the CBFß/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition.

OBJECTIVE: Ovarian cancer survival and treatment have improved minimally in the past 20years. Novel treatment strategies are needed to combat this disease. This study investigates the effects of chemical inhibition of the CBFß/RUNX protein-protein interaction on ovarian cancer cell lines. METHODS: Ovarian cancer cell lines were treated with CBFß/RUNX inhibitors, and the effects on proliferation, DNA replication, wound healing, and anchorage-independent growth were measured. RNA-Seq was performed on compound-treated cells to identify differentially expressed genes. Genes altered by compound treatment were targeted with siRNAs, and effects on DNA replication and wound healing were measured. RESULTS: Chemical inhibition of the CBFß/RUNX interaction decreases ovarian cancer cell proliferation. Inhibitor treatment leads to an S-phase cell cycle delay, as indicated by an increased percentage of cells in S-phase, and a decreased DNA replication rate. Inhibitor treatment also reduces wound healing and anchorage-independent growth. RNA-Seq on compound-treated cells revealed changes in a small number of genes related to proliferation and epithelial-to-mesenchymal transition. siRNA-mediated knockdown of INHBA and MMP1 - two genes whose expression decreases with compound treatment - slowed DNA replication and impaired wound healing. CONCLUSIONS: Chemical inhibition of the CBFß/RUNX interaction is a viable strategy for the treatment of ovarian cancer.