Facilitators and Barriers to Breastfeeding Among Veterans Using Veterans Affairs Maternity Care Benefits.

INTRODUCTION: U.S. veterans of childbearing age represent one of the fastest growing populations using Veterans Affairs (VA) health care. The VA does not provide obstetric care directly but pays for VA-enrolled veterans to obtain outside obstetric care. The VA also provides maternity care coordination (MCC) services, including lactation support. Breastfeeding benefits mothers and babies; however, previous research shows that veteran mothers quit exclusive breastfeeding earlier than the American Academy of Pediatrics and World Health Organization recommendation of 6 months. This study aimed to understand facilitators and barriers to breastfeeding among a cohort of veterans who used VA maternity care benefits. METHODS: Qualitative data from an open-ended question from a national sample of postpartum veterans using VA pregnancy benefits were coded using deductive and inductive content analysis within a matrix framework. Quantitative data were used to contextualize the responses. RESULTS: Four themes emerged from the data: (1) impacts on health of baby/mother; (2) the ability to breastfeed; (3) early postnatal experiences breastfeeding; and (4) cost/convenience. Among those who responded to the open-ended breastfeeding question (329/669), most participants (n = 316; 96%) attempted breastfeeding their current baby. Respondents who did not initiate breastfeeding or who discontinued breastfeeding earlier than planned cited diverse reasons. These included low milk supply, poor latch, nipple pain, mental health factors, and low confidence in their ability to continue breastfeeding. Participants cited the MCC program as a facilitator to breastfeeding, and non-VA hospital experiences were mentioned as barriers. CONCLUSION: Veterans in this cohort of 329 veterans who responded to an open-ended breastfeeding question wanted and attempted to breastfeed; however, barriers such as lactation challenges and unsupportive health care providers made it difficult to continue the practice. As the MCC program grows to include more lactation professionals, MCCs may address barriers such as lactation challenges and unsupportive non-VA health care providers. Further program development should focus on addressing these challenges prenatally.

Predicting success in Cu-catalyzed C-N coupling reactions using data science.

Data science is assuming a pivotal role in guiding reaction optimization and streamlining experimental workloads in the evolving landscape of synthetic chemistry. A discipline-wide goal is the development of workflows that integrate computational chemistry and data science tools with high-throughput experimentation as it provides experimentalists the ability to maximize success in expensive synthetic campaigns. Here, we report an end-to-end data-driven process to effectively predict how structural features of coupling partners and ligands affect Cu-catalyzed C-N coupling reactions. The established workflow underscores the limitations posed by substrates and ligands while also providing a systematic ligand prediction tool that uses probability to assess when a ligand will be successful. This platform is strategically designed to confront the intrinsic unpredictability frequently encountered in synthetic reaction deployment.

Psychiatric inpatient services in Ontario, 2019-2021: a cross-sectional comparison of admissions, diagnoses and acuity during the COVID-19 prerestriction, restriction and postrestriction periods.

BACKGROUND: The COVID-19 pandemic was associated with increased mental health problems in the general population, yet psychiatric hospital admissions decreased. Early evidence suggested that psychiatric admissions normalized within weeks; we sought to examine the longer-lasting impacts on the psychiatric inpatient population beyond this initial period. METHODS: We compared Ontario Mental Health Reporting System admission data for patients admitted to 8 psychiatric hospitals in Ontario, Canada, between 3 time periods - before restrictions were imposed (June 22, 2019, to Mar. 16, 2020), during restrictions (Mar. 17 to June 21, 2020) and after restrictions were lifted (June 22, 2020, to Mar. 16, 2021) for changes in involuntary status, diagnoses and clinical presentation using descriptive analysis. For clinical presentation, we extracted scores on 4 Resident Assessment Instrument-Mental Health symptom scales (Depressive Severity Index, Cognitive Performance Scale, Positive Symptoms Scale-Long Version and Social Withdrawal Scale), and 2 behaviour scales (Aggressive Behavior Scale and Violence Sum). RESULTS: A cross-sectional sample of 9848 patients was included in the analysis. The mean number of daily admissions decreased 19% from 16.4 (standard deviation [SD] 8.0) before the restriction period to 13.3 (SD 6.1) during the restriction period, and was still 6% below prerestriction levels after restrictions were lifted 15.4 (SD 6.8), with standard error difference of 1.03 (95% confidence interval -0.22 to 2.29). From the pre- to the postrestriction periods, the proportion of involuntary patients increased by 6 percentage points, and the proportions of patients diagnosed with a psychotic disorder or personality disorder increased by 4 percentage points and 1 percentage point, respectively. INTERPRETATION: Psychiatric admissions did not fully return to prerestriction levels in absolute rates and patient acuity after COVID-19 restrictions were lifted. Psychiatric services must prepare to appraise and respond to any increased acuity through interventions for patients, workforce planning and mental health support for staff.

Data Science Enables the Development of a New Class of Chiral Phosphoric Acid Catalysts.

The widespread success of BINOL-chiral phosphoric acids (CPAs) has led to the development of several high molecular weight, sterically encumbered variants. Herein, we disclose an alternative, minimalistic chiral phosphoric acid backbone incorporating only a single instance of point chirality. Data science techniques were used to select a diverse training set of catalysts, which were benchmarked against the transfer hydrogenation of an 8-aminoquinoline. Using a univariate classification algorithm and multivariate linear regression, key catalyst features necessary for high levels of selectivity were deconvoluted, revealing a simple catalyst model capable of predicting selectivity for out-of-set catalysts. This workflow enabled extrapolation to a catalyst providing higher selectivity than both reported peptide-type and BINOL-type catalysts (up to 95:5 er). These techniques were then successfully applied towards two additional transforms. Taken together, these examples illustrate the power of combining rational design with data science (ab initio) to efficiently explore reactivity during catalyst development.

Physical Activity and Social Interaction among Rural Older Adults in Saskatchewan during COVID-19.

Physical activity and social interaction among rural older adults are important, particularly during the COVID-19 pandemic when restrictions on physical gatherings were placed. The purpose of this qualitative study was to gain a deeper understanding of rural older adults' experience with physical activity and social interaction during the COVID-19 pandemic. An interpretative phenomenological approach was used to explore the experience of 10 older adults, 67-82 years of age, from rural communities throughout Saskatchewan. Findings revealed that many rural older adults acknowledged the health benefits of physical and social activities and experienced loneliness when COVID-19 restrictions were placed, even when living with a partner. For some, the restrictions placed on physical and social activity provided a welcome break from daily responsibilities. Rural communities, often at a disadvantage, were also perceived by participants as being protected against COVID-19. The resilience demonstrated among rural participants to persevere and adapt to their changing environment during the pandemic was evident in the findings.

Perinatal Depression Treatment Guidelines for Obstetric Providers.

Perinatal depression is the occurrence of depressive symptoms during the antenatal or postnatal period with an annual incidence of 10% to 20%. The consequences of untreated perinatal depression are significant and include negative impacts on maternal health, pregnancy outcomes, and maternal-infant outcomes. The purpose of this article is to provide perinatal pharmacologic and psychological treatment information to help first-line providers more confidently manage depression in the perinatal period. Treatment strategies including medication management using risk versus risk conversations, psychotherapy, and colocated perinatal mental health clinics are discussed.

COVID-19-related anxiety and the role of social media among Canadian youth.

Background: Current literature indicates that safety measures, including lockdowns during the COVID-19 pandemic, severely disrupted our lifestyle, marked by increased screen time. The increased screen time is mostly associated with exacerbated physical and mental wellbeing. However, the studies that examine the relationship between specific types of screen time and COVID-19-related anxiety among youth are limited. Methods: We examined the usage of passive watching, social media, video games, and educational screen time and COVID-19-related anxiety at the 5-time points (Early-Spring 2021, Late-Spring 2021, Fall 2021, Winter 2022, and Spring 2022) among youth in Southern Ontario, Canada (N = 117, mean age = 16.82, male = 22%, non-White = 21%) and investigated the role of 4 types of screen time in COVID-19 related anxiety. COVID-related anxiety was measured using the Coronavirus Anxiety Scale (CAS). Descriptive statistics examined the binary relationships between demographic factors, screen time, and COVID-related anxiety. Also, partially adjusted and fully adjusted binary logistic regression analyses were conducted to examine the association between the types of screen time and COVID-19-related anxiety. Results: During the late Spring of 2021, when the provincial safety restrictions were most stringent, screen time was the highest among the 5 data collection time points. Further, adolescents experienced the highest COVID-19-related anxiety during this period. On the other hand, young adults experienced the highest COVID-19-related anxiety during Spring 2022. In a partially adjusted model (accounting for other types of screen time), engaging in 1-5 h per day on social media increased the likelihood of experiencing COVID-19-related anxiety compared to those who spend less than 1 h per day (OR = 3.50, 95%CI = 1.14-10.72, p < 0.05). Other types of screen time was not significantly associated with COVID-19-related anxiety. In a fully adjusted model (accounting for age, sex and ethnicity besides four types on screen time), 1-5 h per day of social media remained significantly associated with COVID-19-related anxiety (OR = 4.08, 95%CI = 1.22-13.62, p < 0.05). Conclusion: Our findings suggest that COVID-19-related anxiety is associated with youth engagement in social media during the COVID-19 pandemic. Clinicians, parents, and educators should work collaboratively to provide developmentally appropriate approaches to reduce the negative social media impact on COVID-19-related anxiety and promote/foster resiliency in our community during the recovery period.

Multivariate associations between dopamine receptor availability and risky investment decision-making across adulthood.

Enhancing dopamine increases financial risk taking across adulthood but it is unclear whether baseline individual differences in dopamine function are related to risky financial decisions. Here, thirty-five healthy adults completed an incentive-compatible risky investment decision task and a PET scan at rest using [11C]FLB457 to assess dopamine D2-like receptor availability. Participants made choices between a safe asset (bond) and a risky asset (stock) with either an expected value less than the bond ("bad stock") or expected value greater than the bond ("good stock"). Five measures of behavior (choice inflexibility, risk seeking, suboptimal investment) and beliefs (absolute error, optimism) were computed and D2-like binding potential was extracted from four brain regions of interest (midbrain, amygdala, anterior cingulate, insula). We used canonical correlation analysis to evaluate multivariate associations between decision-making and dopamine function controlling for age. Decomposition of the first dimension (r = 0.76) revealed that the strongest associations were between measures of choice inflexibility, incorrect choice, optimism, amygdala binding potential, and age. Follow-up univariate analyses revealed that amygdala binding potential and age were both independently associated with choice inflexibility. The findings suggest that individual differences in dopamine function may be associated with financial risk taking in healthy adults.

Increased cognitive effort costs in healthy aging and preclinical Alzheimer's disease.

Life-long engagement in cognitively demanding activities may mitigate against declines in cognitive ability observed in healthy or pathological aging. However, the "mental costs" associated with completing cognitive tasks also increase with age and may be partly attributed to increases in preclinical levels of Alzheimer's disease (AD) pathology, specifically amyloid. We test whether cognitive effort costs increase in a domain-general manner among older adults, and further, whether such age-related increases in cognitive effort costs are associated with working memory (WM) capacity or amyloid burden, a signature pathology of AD. In two experiments, we administered a behavioral measure of cognitive effort costs (cognitive effort discounting) to a sample of older adults recruited from online sources (Experiment 1) or from ongoing longitudinal studies of aging and dementia (Experiment 2). Experiment 1 compared age-related differences in cognitive effort costs across two domains, WM and speech comprehension. Experiment 2 compared cognitive effort costs between a group of participants who were rated positive for amyloid relative to those with no evidence of amyloid. Results showed age-related increases in cognitive effort costs were evident in both domains. Cost estimates were highly correlated between the WM and speech comprehension tasks but did not correlate with WM capacity. In addition, older adults who were amyloid positive had higher cognitive effort costs than those who were amyloid negative. Cognitive effort costs may index a domain-general trait that consistently increases in aging. Differences in cognitive effort costs associated with amyloid burden suggest a potential neurobiological mechanism for age-related differences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PTSD, depression, and suicidality among survivors of childhood sexual trauma (CST), military sexual trauma (MST), and sexual revictimization (CST + MST).

OBJECTIVE: Research to date has not examined how childhood sexual trauma (CST) followed by sexual trauma during military service (MST) relates to posttraumatic stress disorder (PTSD), depression, and suicidality among women and men. Given the strong association between MST in particular, and these serious posttraumatic outcomes, the current study sought to address this gap. METHOD: The current study compared the mental health concerns of 268 treatment-seeking veterans who were survivors of CST, MST, or both (CST + MST). We hypothesized that MST would be associated with greater severity of symptoms compared with CST and that those who experienced sexual revictimization (CST + MST) would report more severe symptoms than veterans who experienced CST or MST alone. RESULTS: Veteran men presented with significantly higher suicidality but not higher PTSD or depression scores than women. Controlling for gender, MST survivors had significantly higher PTSD and depression symptom severity scores, but not suicidality, than CST survivors. PTSD, depression, and suicidality scores were significantly higher for the CST + MST group than for CST only survivors, but did not significantly differ from survivors of MST alone. CONCLUSION: Findings support the more severe clinical impact of CST + MST-specific sexual revictimization compared with CST-only among military men and women, but also suggest that MST alone can have negative consequences similar to revictimization. While results point to the need to consider context and trauma history in future trauma research and clinical applications, they should be interpreted in light of our sample demographics, which were representative of the southwest U.S. veteran population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cognitive Effort-Based Decision-Making Across Experimental and Daily Life Indices in Younger and Older Adults.

OBJECTIVES: The study investigated whether cognitive effort decision-making measured via a neuroeconomic paradigm that manipulated framing (gain vs. loss outcomes), could predict daily life engagement in mentally demanding activities in both younger and older adults. METHOD: Younger and older adult participants (N = 310) completed the Cognitive Effort Discounting paradigm (Cog-ED), under both gain and loss conditions, to provide an experimental index of cognitive effort costs for each participant in each framing condition. A subset of participants (N = 230) also completed a 7-day Ecological Momentary Assessment (EMA) protocol measuring engagement in mentally demanding daily life activities. RESULTS: In a large, online sample, we replicated a robust increase in cognitive effort costs among older, relative to younger, adults. Additionally, costs were found to be reduced in the loss relative to gain frame, although these effects were only reliable at high levels of task difficulty and were not moderated by age. Critically, participants who had lower effort costs in the gain frame tended to report engaging in more mentally demanding daily life activities, but the opposite pattern was observed in the loss frame. Further analyses demonstrated the specificity of reward-related cognitive motivation in predicting daily life mentally demanding activities. DISCUSSION: Together, these results suggest that cognitive effort costs, as measured through behavioral choice patterns in a neuroeconomic decision-making task, can be used to predict and explain engagement in mentally demanding activities during daily life among both older and younger adults.

An fMRI protocol for administering liquid incentives to human participants.

This protocol describes the materials and approaches for administering liquid incentives to human participants during fMRI scanning. We first describe preparation of the liquid solutions (e.g., neutral solution and saltwater) and liquid delivery setups. We then detail steps to connect the setups to the computer-controlled syringe pump in the MRI control room, followed by procedures for testing the syringe pump dispensing a liquid bolus during the task. Description of custom software and required adapters for implementing the liquid setup are included. For complete details on the use and execution of this protocol, please refer to Yee et al. (2021).

Role of an Online Skill-Based Mindfulness Program for Healthcare Worker's Resiliency During the COVID-19 Pandemic: A Mixed-Method Study.

The COVID-19 pandemic has highlighted the mental health care needs of health care workers. The primary aim of this study was to explore the effects of an online mindfulness program on resiliency in health care workers during the pandemic using a mixed-methods approach. An online 4-week mindfulness program was delivered to healthcare workers (N = 130) in Ontario, Canada. Resiliency was assessed at 3-time points (i.e., pre, post, and 1-month follow-up), and the mindfulness program's efficacy on resiliency was analyzed using linear regression. Semi-structured interviews (N = 10) were conducted to substantiate their experiences. Healthcare workers' resiliency significantly increased after the mindfulness program compared to the baseline, maintaining the effect after 1 month in both unadjusted and adjusted regression models. These findings were further bolstered by the positive experiences shared by participants highlighting the program's efficacy on empathy and resiliency. Evidence suggests that mindfulness is associated with promoting resiliency in healthcare workers and may be an important strategy to promote resiliency in this population.

Trends and outcomes of mechanically ventilated cirrhotic patients in the United States from 2005-2014.

Purpose: Cirrhotic patients in organ failure are frequently admitted to intensive care units (ICUs) to receive invasive mechanical ventilation (IMV). We evaluated the trends of hospitalizations, in-hospital mortality, hospital costs, and hospital length of stay (LOS) of IMV patients with cirrhosis. Methods: We analyzed the United States National Inpatient Sample from 2005-2014. We selected discharges of IMV adult (≥18 years) patients with cirrhosis using the International Classification of Diseases, 9th Edition, Clinical Modification codes. Trends were assessed using linear regression and joinpoint regression. Results: Between 2005 and 2014, there were approximately 9,441,605 hospitalizations of IMV adult patients, of which 4.7% had cirrhosis. There was an increasing trend in the total number of IMV cirrhotic patient hospitalizations (annual percent change [APC] 7.0%, 95% confidence interval [CI] 6.4%; 7.6%, Ptrend < 0.001). The in-hospital case-fatality ratio declined between 2005-2011 (APC -2.9%, 95% CI, -3.4%; -2.4%, Ptrend < 0.001); however, it remained similar between 2011-2014 (Ptrend = 0.58). The total annual hospital costs of all IMV cirrhotic patients increased from approximately $1.2 billion USD in 2005 to $2.7 billion USD in 2014 (Ptrend < 0.001). The mean hospital costs per patient and mean LOS declined between 2005 and 2014 (Ptrend < 0.001 and Ptrend = 0.01 respectively). Conclusions: The total number of hospitalizations and total annual costs of IMV patients with cirrhosis have been increasing over time. However, past hesitancy around admitting cirrhotic patients to the ICU may need to be tempered by the improving mortality trends in this patient population.

Domain-general cognitive motivation: Evidence from economic decision-making - Final Registered Report.

Stable individual differences in cognitive motivation (i.e., the tendency to engage in and enjoy effortful cognitive activities) have been documented with self-report measures, yet convergent support for a trait-level construct is still lacking. In the present study, we used an innovative decision-making paradigm (COG-ED) to quantify the costs of cognitive effort, a metric of cognitive motivation, across two distinct cognitive domains: working memory (an N-back task) and speech comprehension (understanding spoken sentences in background noise). We hypothesized that cognitive motivation operates similarly within individuals, regardless of domain. Specifically, in 104 adults aged 18-40 years, we tested whether individual differences in effort costs are stable across domains, even after controlling for other potential sources of shared individual variation. Conversely, we evaluated whether the costs of cognitive effort across domains may be better explained in terms of other relevant cognitive and personality-related constructs, such as working memory capacity or reward sensitivity. We confirmed a reliable association among effort costs in both domains, even when these other sources of individual variation, as well as task load, are statistically controlled. Taken together, these results add support for trait-level variation in cognitive motivation impacting effort-based decision making across multiple domains.

Incorporating ecological momentary assessment into multimethod investigations of cognitive aging: Promise and practical considerations.

Ecological momentary assessment (EMA) represents a promising approach to study cognitive aging. In contrast to laboratory-based studies, EMA involves the repeated sampling of experiences in daily life contexts, enabling investigators to gain access to dynamic processes (e.g., situational contexts, intraindividual variability) that are likely to strongly contribute to aging and age-related change across the adult life-span. As such, EMA approaches complement the prevailing research methods in the field of cognitive aging (e.g., laboratory-based paradigms, neuroimaging), while also providing the opportunity to replicate and extend findings from the laboratory in more naturalistic contexts. Following an overview of the methodological and conceptual strengths of EMA approaches in cognitive aging research, we discuss best practices for researchers interested in implementing EMA studies. A key goal is to highlight the tremendous potential for combining EMA methods with other laboratory-based approaches, in order to increase the robustness, replicability, and real-world implications of research findings in the field of cognitive aging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Social Interaction and Physical Activity Among Rural Older Adults: A Scoping Review.

Social interaction and physical activity are critical components in supporting health among older adults, yet rates of activity are low in rural communities. There is significant merit in exploring the relationship between these interrelated concepts. A scoping review was conducted to synthesize existing literature. Search results identified 26 studies meeting inclusion criteria. Findings indicated that social interaction and physical activity were important for many older adults to maintain health; however, not all older adults preferred the social aspect of group-based exercise. Opportunities for physical activity and social interaction were limited based on geographical location and other socioeconomic factors. This was evident in rural communities where populations were lower and education and income levels varied. Differences on the defining role and meaning of physical activity also emerged. Increasing physical activity and social interaction must account for negative associations to address the lower rates of participation among rural older adults.

Biasing the input: A yoked-scientist demonstration of the distorting effects of optional stopping on Bayesian inference.

Prior work by Michael R. Dougherty and colleagues (Yu et al., 2014) shows that when a scientist monitors the p value during data collection and uses a critical p as the signal to stop collecting data, the resulting p is distorted due to Type I error-rate inflation. They argued similarly that the use of a critical Bayes factor (BF(crit)) for stopping distorts the obtained Bayes factor (BF), a position that has met with controversy. The present paper clarified that when BF(crit) is used as a stopping criterion, the sample becomes biased in that data consistent with large effects have a greater chance to be included than do other data, thus biasing the input to Bayesian inference. We report simulations of yoked pairs of scientists in which Scientist A uses BF(crit) to optionally stop, while Scientist B, sampling from the same population, stops when A stops. Thus, optional stopping is compared not to a hypothetical in which no stopping occurs, but to a situation in which B stops for reasons unrelated to the characteristics of B's sample. The results indicated that optional stopping biased the input for Bayesian inference. We also simulated the use of effect-size stabilization as a stopping criterion and found no bias in that case.

Use of a Benchmark Tracking Assessment to Support Expansion of Buprenorphine for Treatment of Opioid Use Disorder in Primary Care.

INTRODUCTION: Barriers to the expansion of opioid use disorder (OUD) treatment in primary care using buprenorphine are well documented. Providers require support along a continuum. A systematic tracking framework to enhance provider progress along this continuum is lacking. METHODS: We developed a benchmark tracking assessment (BTA) as part of data collection in a 5-year study to examine the impact of provider participation in an online intervention to support expansion of buprenorphine treatment for OUD in rural primary care. Providers were contacted via phone every 3 months for up to 2 years to track their advancement along the 5 identified key benchmarks and were offered support for any barriers encountered. RESULTS: Forty-one providers enrolled in the study. Almost half (49%) did not experience a barrier that prevented them from accomplishing their next benchmark. Of the remaining 51% of providers, the majority (75%) experienced barriers early in the training and licensure phases, with most citing lack of time as the main reason. CONCLUSION: The BTA offers a feasible approach to identifying challenges along the training to prescription continuum and facilitated targeted support to address barriers. This framework has the potential, with locally contextual adaptations, to guide medication-assisted treatment implementation and training efforts.

A Phase I Trial of Dasatinib and Osimertinib in TKI Naïve Patients With Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

BACKGROUND: Osimertinib is an effective first-line therapy option for EGFR-mutant NSCLC, but virtually all patients develop resistance. CRIPTO, through Src activation, has been implicated in resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Dasatinib, a Src inhibitor, has shown preclinical synergy with EGFR-TKI therapy. METHOD: This is a single-arm phase I/II trial of osimertinib and dasatinib in TKI-naïve advanced EGFR-mutant NSCLC (NCT02954523). A 3 + 3 design was used in the phase I to establish the recommended phase II dose (RP2D). Osimertinib 80 mg QD was combined with dasatinib 70 mg BID (DL2), 50 mg BID (DL1), 70 mg QD (DL-1), and 50 mg QD (DL-2). RESULTS: Ten patients (DL2: 3, DL1: 6, DL -1: 1) were enrolled. 3 (50%) of 6 patients at DL1 experienced a DLT (grade 3 headaches/body pain, neutropenia, rash, one each). Common treatment-related adverse events included pleural effusion (n=10), diarrhea (n=8), rash (n=7), transaminitis (n=7), thrombocytopenia (n=7), and neutropenia (n=7). While the MTD was not determined by protocol-defined DLT criteria, DL-2 was chosen as the RP2D, considering overall tolerability. Nine (90%) patients had a PR, including 1 unconfirmed PR. Median PFS was 19.4 months and median OS 36.1 months. The trial was closed to accrual prematurely due to slow accrual after the approval of osimertinib as first-line therapy. CONCLUSIONS: The combination of dasatinib and osimertinib demonstrated anticancer activity. The treatment was limited by chronic toxicities mainly attributed to dasatinib. To improve the safety and tolerability of Src and EGFR co-inhibition, Src inhibitors with a more favorable safety profile should be utilized in future studies. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02954523.