Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children.

BACKGROUND: Prior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1ß [IL-1ß], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock). METHODS: We collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors. RESULTS: Our final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging. CONCLUSION: Our findings support prior work suggesting that social stress exposures contribute to increased inflammation in children. IMPACT: Our study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children. CLINICAL TRIAL REGISTRATION: NCT02746393.

Adverse Childhood Experiences and BMI: Lifecourse Associations in a Black-White U.S. Women Cohort.

INTRODUCTION: Although adverse childhood experiences (ACEs) have been positively associated with adiposity, few studies have examined long-term race-specific ACE-BMI relationships. METHODS: A Black and White all-women cohort (N=611; 48.6% Black) was followed between 1987 and 1997 from childhood (ages 9-10 years) through adolescence (ages 19-20 years) to midlife (ages 36-43 years, between 2015 and 2019). In these 2020-2022 analyses, the interaction between race and individual ACE exposures (physical abuse, sexual abuse, household substance abuse, multiple ACEs) on continuous BMI at ages 19-20 years and midlife was evaluated individually through multivariable linear regression models. Stratification by race followed as warranted at α=0.15. RESULTS: Race only modified ACE-BMI associations for sexual abuse. Among Black women, sexual abuse was significantly associated with BMI (Badjusted=3.24, 95% CI=0.92, 5.57) at ages 19-20 years and marginally associated at midlife (Badjusted=2.37, 95% CI= -0.62, 5.35); among White women, corresponding associations were null. Overall, having ≥2 ACEs was significantly associated with adolescent BMI (Badjusted=1.47, 95% CI=0.13, 2.80) and was marginally associated at midlife (Badjusted=1.45, 95% CI= -0.31, 3.22). This was similarly observed for physical abuse (adolescent BMI: Badjusted=1.23, 95% CI= -0.08, 2.54; midlife BMI: Badjusted=1.03, 95% CI= -0.71, 2.78), but not for substance abuse. CONCLUSIONS: Direct exposure to certain severe ACEs is associated with increased BMI among Black and White women. It is important to consider race, ACE type, and life stage to gain a more sophisticated understanding of ACE-BMI relationships. This knowledge can help strengthen intervention, prevention, and policy efforts aiming to mitigate the impacts of social adversities and trauma on persistent cardiometabolic health disparities over the lifecourse.

Cohort profile: the longitudinal National Growth and Health Study (NGHS) of black and white girls from Northern California tracking how behavioural and psychosocial risk factors predict cardiovascular risk and biological ageing in midlife and in offspring.

PURPOSE: The National Heart, Lung and Blood Institute Growth and Health Study (NGHS) prospectively collected anthropometric, biospecimens, clinical, health behaviour and psychosocial measures associated with cardiovascular disease from childhood to young adulthood. The aim of the current study was to assess the impact of stress, dysregulated eating and social genomic biomarkers on cardiometabolic risk factors among the original participants now in midlife and their children. PARTICIPANTS: Beginning in 1987-1988, NGHS recruited black and white girls (age 9-10 years) from socioeconomically diverse backgrounds from from three sites: Cincinnati, Ohio; Washington, DC; and Western Contra Costa County, California (N=2379) and followed them for 10 years. The study maintained an 89% retention rate. The current study is 30 years after the start of the original study and focused on the participants of California (n=887) and their children aged 2-17 years. We re-enrolled 624 of 852 eligible participants (73%): 49.2% black and 50.8% white. The mean age was 39.5 years. Among the 645 eligible biological children, 553 were enrolled; 49% black and 51% white, with 51.5% girls and 48.5% boys. The mean age was 9.3 years. FINDINGS TO DATE: Longitudinal analysis of adolescent drive for thinness predicted higher scores for drive for thinness during midlife, which was indirectly associated with greater adult body mass index through adult drive for thinness. Latent trajectory modelling of adolescent growth over 10 years found that women with persistently high weight trajectory had twice the odds of having children who met the definition for obesity compared with the persistently normal group, adjusting for adult weight. FUTURE PLANS: New studies on neighbourhood socioeconomic status, food insecurity and additional biomarkers of chronic stress, microbiome and accelerated ageing (ie, telomere length and epigenetic clock) are underway. We are developing a 10-year follow-up to understand changes in ageing biomarkers of the participants and their children. TRIAL REGISTRATION NUMBER: NCT00005132.

Eviction filings during bans on enforcement throughout the COVID-19 pandemic: an interrupted time series analysis.

OBJECTIVE: Bans on evictions were implemented to reduce the spread of COVID-19 and to protect vulnerable populations during a public health crisis. Our objective was to examine how three bans on eviction enforcement impacted eviction filings from March 2020 through January 2022 in Ontario, Canada. METHODS: Data were derived from eviction application records kept by the Ontario Landlord and Tenant Board. We used segmented regression analysis to model changes in the average weekly filing rates for evictions due to non-payment of rent (L1 filings) and reasons other than non-payment of rent (L2 filings). RESULTS: The average number of weekly L1 and L2 applications dropped by 67.5 (95% CI: 55.2, 79.9) and 31.7 (95% CI: 26.7, 36.6) filings per 100,000 rental dwellings, respectively, following the first ban on eviction enforcement (p < 0.0001). Notably, they did not fall to zero. Level changes during the second and third bans were insubstantial and slope changes for L2 applications varied throughout the study period. The L1 filing rate appeared to increase towards the end of the study period (slope change: 1.3; 95% CI: 0.1, 2.6; p = 0.0387). CONCLUSION: Our findings suggest that while the first ban on eviction enforcement appeared to substantially reduce filing rates, subsequent bans were less effective and none of them eliminated eviction filings altogether. Enacting upstream policies that tackle the root causes of displacement would better equip jurisdictions during future public health emergencies.

RéSUMé: OBJECTIF: Les ordonnances d'expulsion résidentielles ont été suspendues pour réduire la propagation de la COVID-19 et pour protéger les populations vulnérables pendant une crise de santé publique. Notre objectif était d'examiner l'impact de trois interdictions d'exécution d'ordonnance d'éviction sur les requêtes d'expulsion de mars 2020 à janvier 2022 en Ontario, au Canada. MéTHODES: Les données ont été tirées des dossiers de requêtes d'expulsion conservés par la Commission de la location immobilière de l'Ontario. Nous avons utilisé une analyse de régression segmenté pour modéliser les changements dans les taux hebdomadaires moyens de requêtes d'expulsion pour non-paiement du loyer (requêtes L1) et pour des raisons autres que le non-paiement du loyer (requêtes L2). RéSULTATS: Le nombre moyen de demandes hebdomadaires de dépôts de requêtes L1 et L2 a chuté de 67,5 % (IC à 95% : 55,2, 79,9) et de 31,7 % (IC à 95% : 26,7, 36,6) pour 100 000 logements locatifs, respectivement, suite à la première interdiction d'exécution des expulsions. Il est à noter qu'elles ne sont pas tombées à zéro. Les changements du taux de requêtes au cours de la deuxième et la troisième interdictions n'étaient pas substantiels et les changements de pente pour les applications L2 ont varié tout au long de la période d'étude. Le taux de dépôt de L1 a semblé augmenter vers la fin de la période d'étude (changement de pente : 1,3; IC à 95% : 0,1, 2,6; p = 0,0387). CONCLUSION: Nos résultats suggèrent qu'alors que la première interdiction d'exécution des expulsions a semblé réduire considérablement les taux de dépôt d'expulsion, les interdictions ultérieures ont été moins efficaces et aucune d'entre elles n'a complètement éliminé les dépôts d'expulsion. L'adoption de politiques en amont qui s'attaquent plutôt aux causes profondes des expulsions permettrait de mieux équiper les juridictions lors de futures urgences de santé publique.

Assessing Implementation of Social Screening Within US Health Care Settings: A Systematic Scoping Review.

PURPOSE: Though a growing crop of health care reforms aims to encourage health care-based social screening, no literature has synthesized existing social screening implementation research to inform screening practice and policymaking. METHODS: Systematic scoping review of peer-reviewed literature on social screening implementation published 1/1/2011-2/17/2022. We applied a 2-concept search (health care-based screening; social risk factors) to PubMed and Embase. Studies had to explore the implementation of health care-based multi-domain social screening and describe 1+ outcome related to the reach, adoption, implementation, and/or maintenance of screening. Two reviewers extracted data related to key study elements, including sample, setting, and implementation outcomes. RESULTS: Forty-two articles met inclusion criteria. Reach (n = 7): We found differences in screening rates by patient race/ethnicity; findings varied across studies. Patients who preferred Spanish had lower screening rates than English-preferring patients. Adoption (n = 13): Workforce education and dedicated quality improvement projects increased screening adoption. Implementation (n = 32): Time was the most cited barrier to screening; administration time differed by tool/workforce/modality. Use of standardized screening tools/workflows improved screening integration. Use of community health workers and/or technology improved risk disclosure and facilitated screening in resource-limited settings. Maintenance (n = 1): Only 1 study reported on maintenance; results showed a drop in screening over 21 months. CONCLUSIONS: Critical evidence gaps in social screening implementation persist. These include gaps in knowledge about effective strategies for integrating social screening into clinical workflows and ways to maximize screening equity. Future research should leverage the rapidly increasing number of screening initiatives to elevate and scale best practices.

Atezolizumab-associated myositis in a patient with unresectable hepatocellular carcinoma.

INTRODUCTION: Combination treatment with atezolizumab and bevacizumab is the preferred first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma with a Child-Pugh Class A liver function. Reactivation of the antitumor immune response with atezolizumab can result in the development of immune-related adverse events including colitis, skin rash, endocrinopathies, pneumonitis, and nephritis with renal dysfunction. However, the occurrence of myositis with immune checkpoint inhibitors is rare. CASE REPORT: We report on a 67-year-old male patient with an initial diagnosis of hepatocellular carcinoma, stage IV, unresectable with underlying cirrhosis who experienced atezolizumab-associated myositis. MANAGEMENT AND OUTCOME: Utilization of the American Society of Clinical Oncology guideline on managing immune checkpoint inhibitors adverse events helped guide the ordering of pertinent labs for monitoring and pharmacologic treatment. In our case, atezolizumab-induced myositis was resolved via a combination of corticosteroids, intravenous immunoglobulins, and plasmapheresis. DISCUSSION: Recognition of the signs and symptoms of atezolizumab-associated myositis is recommended and utilization of the American Society of Clinical Oncology guideline to guide management and treatment of associated symptoms.

Assessing Area-Level Deprivation as a Proxy for Individual-Level Social Risks.

INTRODUCTION: Concerns about the opportunity costs of social screening initiatives have led some healthcare organizations to consider using social deprivation indices (area-level social risks) as proxies for self-reported needs (individual-level social risks). Yet, little is known about the effectiveness of such substitutions across different populations. METHODS: This analysis explores how well the highest quartile (cold spot) of three different area-level social risk measures-the Social Deprivation Index, Area Deprivation Index, and Neighborhood Stress Score-corresponds with six individual-level social risks and three risk combinations among a national sample of Medicare Advantage members (N=77,503). Data were derived from area-level measures and cross-sectional survey data collected between October 2019 and February 2020. Agreement between individual and individual-level social risks, sensitivity values, specificity values, positive predictive values, and negative predictive values was calculated for all measures in summer/fall 2022. RESULTS: Agreement between area and individual-level social risks ranged from 53% to 77%. Sensitivity for each risk and risk category never exceeded 42%; specificity values ranged from 62% to 87%. Positive predictive values ranged from 8% to 70%, and negative predictive values ranged from 48% to 93%. There were modest performance discrepancies across area-level measures. CONCLUSIONS: These findings provide additional evidence that area-level deprivation indices may be inconsistent indicators of individual-level social risks, supporting policy efforts to promote individual-level social screening programs in healthcare settings.

Unmet Social Needs and Patterns of Hair Cortisol Concentration in Mother-Child Dyads.

Background: Mothers and their children demonstrate dyadic synchrony of hypothalamic-pituitary-adrenal (HPA) axis function, likely influenced by shared genetic or environmental factors. Although evidence has shown that chronic stress exposure has physiologic consequences for individuals-including on the HPA axis-minimal research has explored how unmet social needs such as food and housing instability may be associated with chronic stress and HPA axis synchrony in mother-child dyads. Methods: We conducted a secondary analysis of data from 364 mother-child dyads with low-income recruited during a randomized trial conducted in an urban pediatric clinic. We used latent profile analysis (LPA) to identify subgroups based on naturally occurring patterns of within-dyad hair cortisol concentration (HCC). A logistic regression model predicted dyadic HCC profile membership as a function of summative count of survey-reported unmet social needs, controlling for demographic and health covariates. Results: LPA of HCC data from dyads revealed a 2-profile model as the best fit. Comparisons of log HCC for mothers and children in each profile group resulted in significantly "higher dyadic HCC" versus "lower dyadic HCC" profiles (median log HCC for mothers: 4.64 vs 1.58; children: 5.92 vs 2.79, respectively; P < .001). In the fully adjusted model, each one-unit increase in number of unmet social needs predicted significantly higher odds of membership in the higher dyadic HCC profile when compared to the lower dyadic HCC profile (odds ratio = 1.13; 95% confidence interval [1.04-1.23]; P = .01). Conclusion: Mother-child dyads experience synchronous patterns of physiologic stress, and an increasing number of unmet social needs is associated with a profile of higher dyadic HCC. Interventions aimed at decreasing family-level unmet social needs or maternal stress are, therefore, likely to affect pediatric stress and related health inequities; efforts to address pediatric stress similarly may affect maternal stress and related health inequities. Future research should explore the measures and methods needed to understand the impact of unmet social needs and stress on family dyads.

Retrospective study on the efficacy and tolerability of dose modification of PD-1 and PD-L1 inhibitors in hospital-system community outpatient cancer clinics.

BACKGROUND: Anti-programmed cell death (PD)-1 and anti-PD-L1 medications inhibit the PD-1 and PD-L1 interaction and have been shown to be effective in treating several forms of advanced cancers. Since the approval of these agents, standard dosing protocols have been utilized. However, a small population of patients in the community setting has received dose-modified PD-1 and PD-L1 inhibitors secondary to a lack of tolerability. Data from this study suggests possible benefit with different dosing strategies. OBJECTIVES: The purpose of this retrospective study is to assess the efficacy and tolerability in terms of time to progression and adverse effects in patients receiving dose-modified PD-1 and PD-L1 inhibitors in Food and Drug Administration (FDA)-labeled indications. METHODS: This single-institution retrospective chart review was conducted in an outpatient community setting on patients with cancer that received nivolumab, pembrolizumab, durvalumab, or atezolizumab for an FDA indication at one of the Houston Methodist Hospital infusion clinic site between September 1, 2017 and September 30, 2019. Data collection included demographics, adverse effects, dosing, treatment delay, and number of immunotherapy cycles administered per patient. RESULTS: This study included 221 patients, who received either nivolumab (n = 81), pembrolizumab (n = 93), atezolizumab (n = 21), or durvalumab (n = 26). There were 11 patients who experienced a dose reduction and 103 patients who experienced a treatment delay. Of the patients with a treatment delay, the median time to progression was 197 days, and for patients with a dose reduction, the median time to progression was 299 days. CONCLUSION: The results of this study found that the immunotherapy associated adverse effects led to dosing and frequency changes for tolerance with continued therapy. Our data suggests that there could be potential benefits of dose modifications to immunotherapy treatment, but further large studies are needed to assess the efficacy of specific immunotherapy dose modifications on both outcomes and adverse effects.

Stakeholder perspectives on social screening in US healthcare settings.

BACKGROUND: Evidence on the health impacts of social conditions has led US healthcare systems to consider identifying and addressing social adversity-e.g. food, housing, and transportation insecurity-in care delivery settings. Social screening is one strategy being used to gather patient information about social circumstances at the point of care. While several recent studies describe the rapid proliferation of social screening activities, little work has explored either why or how to implement social screening in clinical settings. Our study objectives were to assess diverse healthcare stakeholder perspectives on both the rationale for social screening and evidence needed to inform practice and policy-relevant implementation decisions. METHODS: We convened five focus groups with US experts representing different stakeholder groups: patient advocates, community-based organizations, healthcare professionals, payers, and policymakers. In total, 39 experts participated in approximately 90-minute long focus groups conducted between January-March 2021. A inductive thematic analysis approach was used to analyze discussions. RESULTS: Three themes emerged from focus groups, each reflecting the tension between the national enthusiasm for screening and existing evidence on the effectiveness and implementation of screening in clinical settings: (1) ambiguity about the rationale for social screening; (2) concerns about the relavence of screening tools and approaches, particularly for historically marginalized populations; (3) lack of clarity around the resources needed for implementation and scaling. CONCLUSION: While participants across groups described potential benefits of social screening, they also highlighted knowledge gaps that interfered with realizing these benefits. Efforts to minimize and ideally resolve these knowledge gaps will advance future social screening practice and policy.

Patient and Patient Caregiver Perspectives on Social Screening: A Review of the Literature.

BACKGROUND: Health care policy and practice-level enthusiasm around social screening has emerged in the absence of a clear appreciation for how patients feel about these activities. Yet patient and caregiver perspectives should be used to establish the rationale and inform the design and implementation of social screening initiatives. METHODS: We conducted a systematic scoping review to better understand patient and patient caregiver perspectives regarding multidomain social screening in US health care settings. RESULTS: We identified 16 articles. Thirteen studies assessed the perspectives of patients; a partially overlapping 9 studies assessed the perspectives of adult patient caregivers. Most articles assessing the acceptability of social screening reported that patients and patient caregivers generally found it to be acceptable. Notably, there was some variation by screening approach and prior experiences in health care settings, as well as mixed findings by race/ethnicity and gender. Participants from several articles raised concerns regarding data documentation and sharing, highlighting the potential for social data to contribute to provider bias. CONCLUSION: The themes emerging in this diverse set of largely descriptive studies warrant deeper and more rigorous exploration as social screening initiatives expand in health care settings across the United States.

Understanding Take-Up Of The Earned Income Tax Credit Among Californians With Low Income.

The Earned Income Tax Credit (EITC) is the largest poverty alleviation program for families with children in the US, and it has well-documented health effects. However, not all eligible families receive benefits. The Assessing California Communities' Experiences with Safety Net Supports (ACCESS) Study interviewed 411 EITC-eligible Californians with young children to understand low take-up of the federal EITC and California's supplemental CalEITC. Interviews were conducted in English and Spanish in 2020 and 2021 to gather information on sociodemographic characteristics, tax filing, and EITC receipt (verified via tax forms). Among those eligible for the EITC or CalEITC, 9 percent of participants did not file taxes; among those who did file taxes, about 84 percent received the EITC, and 83 percent received the CalEITC. Lower likelihood of federal EITC receipt among those eligible and filing taxes was associated with being younger, not speaking English, and not having prior knowledge of the EITC. Lower likelihood of CalEITC receipt among those eligible and filing taxes was associated with not speaking English. These findings can inform policies and community interventions to increase EITC take-up and thereby help address health equity.

Pan-Canadian consensus recommendations for proton beam therapy access in Canada.

PURPOSE: Proton Beam Therapy (PBT)is a treatment option for select cancer patients. It is currently not available in Canada. Assessment and referral processes for out-of-country treatment for eligible patients vary by jurisdiction, leading to variability in access to this treatment for Canadian cancer patients. The purpose of this initiative was to develop a framework document to inform consistent and equitable PBT access for appropriate patients through the creation of pan-Canadian PBT access consensus recommendations. MATERIALS AND METHODS: A modified Delphiprocess was used to develop pan-Canadian recommendations with input from 22 PBT clinical and administrative experts across all provinces, external peer-review by provincial cancer and system partners, and feedback from a targeted community consultation. This was conducted by electronic survey and live discussion. Consensus threshold was set at 70% agreement. RESULTS: Fourconsensus rounds resulted in a final set of 27 recommendations divided into three categories: patient eligibility (n = 9); program level (n = 10); and system level (n = 8). Patient eligibility included: anatomic site (n = 4), patient characteristics (n = 3), clinical efficacy (n = 2). Program level included: regulatory and staff requirements (n = 5), equipment and technologies (n = 4), quality assurance (n = 1). System level included: referral process (n = 5), costing, budget impact and quality adjusted life years (n = 2), eligible patient estimates (n = 1). Recommendations were released nationally in June 2021 and distributed to all 43 cancer programs in Canada. CONCLUSION: A pan-Canadian consensus-building approach was successful in creating an evidence-based, peer-reviewed suite of recommendations thatsupportapplication of consistent clinical criteria to inform treatment options, facility set-up and access to high quality proton therapy.

Pandemic-related socioeconomic disruptions and adverse health outcomes: a cross-sectional study of female caregivers.

BACKGROUND: The COVID-19 pandemic and efforts to mitigate transmission resulted in sudden and widespread socioeconomic disruptions including school and child care closures, unemployment and underemployment, and housing precarity. Understanding the extent to which these disruptions may have contributed to adverse health outcomes is critical for establishing policy priorities that can mitigate further harm. METHODS: We explored the associations between pandemic-related child care, employment, and housing disruptions with depressive symptoms, self-rated health, and food security status among a sample of economically disadvantaged and racially diverse female caregivers of young children (n=464). Data were derived from the Assessing California Communities' Experiences with Safety Net Supports (ACCESS) study, which conducted survey-based interviews with California caregivers with low-income from August 2020 - May 2021. We implemented a series of multivariable Poisson regressions with robust standard errors to assess the potency of each exposure, independently and within the context of one another. RESULTS: Most caregivers experienced disruptions to child care (70%) and employment (63%); few experienced major housing disruptions (8%). Women that experienced child care and housing disruptions had greater depressive symptoms, lower self-rated health, and greater food insecurity, although the relationships for housing and depressive symptoms were modified by the timing of participants' interviews. Employment disruptions were not associated with any of the examined adverse health outcomes. CONCLUSION: In the wake of socioeconomic stressors brought about by the COVID-19 pandemic, attending to structural deficits in the child care system and increasing housing supports may be critical for protecting the health of caregivers.

Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1.

RAD51 is a critical recombinase that functions in concert with auxiliary mediator proteins to direct the homologous recombination (HR) DNA repair pathway. We show that Cys319 RAD51 possesses nucleophilic characteristics and is important for irradiation-induced RAD51 foci formation and resistance to inhibitors of poly (ADP-ribose) polymerase (PARP). We have previously identified that cysteine (Cys) oxidation of proteins can be important for activity and modulated via binding to peroxiredoxin 1 (PRDX1). PRDX1 reduces peroxides and coordinates the signaling actions of protein binding partners. Loss of PRDX1 inhibits irradiation-induced RAD51 foci formation and represses HR DNA repair. PRDX1-deficient human breast cancer cells and mouse embryonic fibroblasts display disrupted RAD51 foci formation and decreased HR, resulting in increased DNA damage and sensitization of cells to irradiation. Following irradiation cells deficient in PRDX1 had increased incorporation of the sulfenylation probe DAz-2 in RAD51 Cys319, a functionally-significant, thiol that PRDX1 is critical for maintaining in a reduced state. Molecular dynamics (MD) simulations of dT-DNA bound to a non-oxidized RAD51 protein showed tight binding throughout the simulation, while dT-DNA dissociated from an oxidized Cys319 RAD51 filament. These novel data establish RAD51 Cys319 as a functionally-significant site for the redox regulation of HR and cellular responses to IR.

Striving to Fill in Gaps between Clinical Practice and Standards: The Evolution of a Pan-Canadian Approach to Patient-Reported Outcomes Use.

Despite the known importance and necessity of the standardized collection and use of patient-reported outcomes (PROs), there remain challenges to successful clinical implementation. Facilitated through a quality improvement initiative spearheaded by the Canadian Partnership for Quality Radiotherapy (CPQR), and now guided by the Canadian Association of Radiation Oncology (CARO)'s Quality and Standards Committee, patient representatives and early-adopter radiation treatment programs continue to champion the expansion of PROs initiatives across the country. The current review discusses the evolution of a pan-Canadian approach to PROs use, striving to fill in gaps between clinical practice and guideline recommendations through multi-centre and multidisciplinary collaboration.

Patient Engagement: an Assessment of Canadian Radiotherapy Programs' Current Practices, Perceived Barriers, and Facilitators.

Patient engagement and education have been mandated across Canadian radiation oncology programs (ROP). Guidance documents include the 2014 Canadian Association of Radiation Oncology (CARO) Radiation Therapy Patient Charter, the 2016 Canadian Partnership for Quality Radiotherapy (CPQR) Patient Engagement Guidelines (PEG) for Canadian Radiation Treatment Programs, and Accreditation Canada's 2017 refresh of Cancer Care Standards. Since little is known regarding uptake of these guidance statements, Canadian ROP were surveyed to assess current patient engagement and education practices. An e-survey was sent to Canadian ROP (n = 44). The survey focused on awareness and uptake of the CARO Patient Charter, CPQR PEG, and patient education practices. Survey development was guided by these documents and expert consensus, including CARO's Quality and Standards Patient Education/Engagement working group. Many (71%) responding ROP were familiar with the CARO Patient Charter, while 24% reported use. More than half (53%) of ROP were aware of the CPQR PEG, but approximately third (37%) had previously completed a self-audit. Most (88%) ROP view a pan-Canadian, evidence-based approach to educational materials beneficial and feasible (80%), with the majority (89%) willing to share their best practices across the radiotherapy community. Patient engagement and education are nationally mandated and supported by guidance documents. However, gaps have been identified across ROP for awareness and use of available tools, as well as uptake of their processes critical to quality of care. Understanding current practices will inform CPQR/CARO-supported pan-Canadian initiatives to optimize uptake, including development of CPQR Patient Education Guidance for Canadian Radiation Treatment Programs.

Capecitabine-induced leukoencephalopathy in a patient with triple-negative breast cancer: A case report and review of the literature.

INTRODUCTION: Capecitabine is an orally administered prodrug that converts preferentially to 5-fluorouracil within tumors, resulting in enhanced concentrations of 5-fluorouracil in tumor tissue. The use of capecitabine has shown efficacy in the metastatic setting for breast cancer, and more recently, efficacy as adjuvant therapy for triple-negative breast cancer (TNBC). Capecitabine has been shown to be well tolerated with minimal side effects, but the incidence of leukoencephalopathy is rare with a risk of less than one percent. CASE REPORT: We report on a 34-year-old female patient with left TNBC, moderately differentiated, stage IIB that experienced symptoms of neurotoxicity following initiation of adjuvant chemotherapy with capecitabine. MANAGEMENT AND OUTCOME: Naranjo Algorithm Assessment score of nine indicated patient had drug-induced leukoencephalopathy leading to discontinuation of capecitabine and resolution of the neurotoxicity symptoms. DISCUSSION: Early detection of capecitabine-induced neurotoxicity by magnetic resonance imaging is crucial as symptoms may be reversible to the condition that capecitabine is immediately discontinued.

Provincial variations in radiotherapy utilization as a measure of access: A pan-Canadian study.

BACKGROUND AND PURPOSE: Access to radiotherapy (RT) is a key component of a cancer control strategy. However, radiotherapy utilization (RTU) rates fall short of desired benchmarks in certain Canadian provinces. We aimed to describe provincial variations in RTU across Canada. MATERIALS AND METHODS: We calculated radiotherapy utilization ratios (RTUR) for each Canadian province from 2016 (RT case counts divided by incidence counts), by cancer type (all cancers, lung, breast, rectal, prostate) and treatment intent (curative, palliative) where data were available. Data were extracted from each provincial RT data repository, cancer registry and/or RT department. We compared RTURs descriptively across provinces and to Ontario benchmarks, and calculated an estimated national RTUR. In provinces with capacity for data linkage, RTURs were compared to a linked (patient-specific) method of calculating utilization, by linking each incident case to whether RT was received within 1 year of diagnosis (RTU-1 yr). RESULTS: Excluding three provinces that included re-treatments, all-cancer RTURs ranged from 0.31 in Manitoba to 0.40 in Nova Scotia. The national all-cancer RTUR was 0.35, which was comparable to Ontario benchmarks (0.34). Larger variations were seen by cancer type, with an absolute difference in RTURs of 28% for lung cancers, 27% for breast cancers, 21% for rectal cancers, and 18% for prostate cancers. RTURs for nearly all provinces were below established Ontario benchmarks for each cancer type, except prostate cancer. RTURs over-estimated RTU-1 yr by at most 5%, except for prostate cancers where they over-estimated RTU-1 yr by up to 15%. CONCLUSIONS: RTU varies by province in Canada, and most notably by cancer subsite. More granular data at the regional level and by healthcare facility is required to further tailor strategies aimed at improving RT access. RTURs also serve as a reasonable surrogate for linked RTU, and both methods can contribute meaningfully to measure RTU depending on the context and data availability.

The Usefulness of Patient-Reported Outcomes and the Influence on Palliative Oncology Patients and Health Services: A Qualitative Study of the Prospective Outcomes and Support Initiative.

BACKGROUND: Through the British Columbia, Prospective Outcomes and Support Initiative (POSI), registered nurses collect patient-reported outcome (PRO) data during telephone follow-up with palliative oncology patients. OBJECTIVE: The research objective was to describe the usefulness and influence of the nursing care provided through POSI follow-up on palliative patients and health services. METHODS: We used a qualitative interpretive description approach involving the collection and analysis of semistructured interview data with 20 palliative patients and 12 oncology nurses. All participant data were subjected to an inductively derived coding framework. Analytic categories were identified and iteratively revised through constant comparative techniques to develop representative themes. RESULTS: The accounts of patients and nurses suggest that telephone follow-up with PROs enabled the nurses to (1) focus on the priorities of patients experiencing complex health challenges, (2) manage complex symptoms, (3) ease the patient's transition home, and (4) improve access to and use of health services. Suggestions for improving POSI nurse follow-up centered on flexibility in the timing of the follow-up, creating dedicated POSI work assignments, and having additional time to personalize assessments and nursing care beyond the PRO questionnaires. CONCLUSIONS: Nursing care employing PROs via telephone follow-up can improve palliative cancer patients' quality of life and health service use. IMPLICATIONS FOR PRACTICE: Nurses are optimally positioned to use PROs following cancer treatment completion but require organizational resources and support to optimize patient and system outcomes.