Vaccination practices of pediatric oncologists from eight states.

BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.

Beyond Medical Care: How Different National Models of Care Impact the Experience of Adolescent and Young Adult Cancer Patients.

Patient experience is positively associated with clinical effectiveness, quality care, and patient safety. This study examines the experience of care of adolescents and young adult (AYA) cancer patients from Australia and the United States, allowing a comparison of patient experiences in the context of different national models of cancer care delivery. Participants (n = 190) were aged 15-29 years and received cancer treatment from 2014 to 2019. Australians (n = 118) were recruited nationally by health care professionals. U.S. participants (n = 72) were recruited nationally via social media. The survey included demographic and disease variables, and questions regarding medical treatment, information and support provision, care coordination, and satisfaction across the treatment pathway. Sensitivity analyses examined the possible contribution of age and gender. Most patients from both countries were satisfied or very satisfied with their medical treatment (chemotherapy, radiotherapy, and surgery). There were significant differences between countries in the provision of fertility preservation services, age-appropriate communication, and psychosocial support. Our findings suggest when a national system of oversight with both state and federal funding is implemented, as is the case in Australia but not in the United States, significantly more AYAs with cancer receive age-appropriate information and support services, and improved access to specialist services such as fertility care. A national approach with government funding and centralized accountability appears to be associated with substantial benefits for the well-being of AYAs undergoing cancer treatment.

A scoping review of the individual, socio-cultural, environmental and commercial determinants of gambling for older adults: implications for public health research and harm prevention.

Gambling is a global public health issue that can cause harm to individuals, families, and communities. Older adults are vulnerable to gambling harm due to life-stage experiences. This study aimed to examine current research relating to individual, socio-cultural, environmental, and commercial determinants of gambling among older adults. A scoping review was conducted (PubMed, PsycInfo, SocIndex, CINAHL Complete, Web of Science, Social Science and Sociology databases available in ProQuest, Google Scholar, citation searching), with peer reviewed studies included that were published between 1 December 1999 and 28 September 2022. Included studies were published in English in peer-reviewed journals that examined the determinants of gambling in adults aged 55 and over. Records were excluded if they were experimental studies, prevalence studies or had a population wider than the required age group. Methodological quality was assessed using JBI critical appraisal tools. Data was extracted using a determinants of health framework and common themes were identified. Forty-four were included. Most literature examined individual and socio-cultural determinants including reasons for gambling, risk management strategies, and social motivations for gambling. Few studies investigated environmental or commercial determinants, and those that did focused on accessibility of venues or promotions as pathways to gambling. Further research is needed to understand the impact of gambling environments and industry, and effective public health responses for older adults.

Inclusion of a core patient-reported outcomes battery in adolescent and young adult cancer clinical trials.

Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute's Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer.

Pericytes take up and degrade α-synuclein but succumb to apoptosis under cellular stress.

Parkinson's disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood-brain barrier, controlling blood flow and mediating inflammation. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin-proteasome system. Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor-MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. These results suggest that the observed accumulation of α-syn in pericytes in human PD brains likely plays a role in PD pathogenesis, perhaps by causing cerebrovascular instability, under conditions of cellular stress.

Care Experience, by Site of Care, for Adolescents and Young Adults With Cancer.

PURPOSE: Most of the 77,000 adolescents and young adults (AYAs) 15-39 years of age diagnosed with cancer annually in the United States are treated at community rather than academic centers. Little is known about their healthcare experience. METHODS: A cross-sectional, anonymous, online survey was conducted with a convenience sample of AYAs treated for cancer at US academic (n = 112) or community centers (n = 64). RESULTS: Clinical trials were offered more frequently to respondents treated at academic centers (26.8% v 7.8%; P = .005). Eighty percent of all those offered a clinical trial chose to enroll. Over three-fourths reported awareness of community-based or online AYA oncology support services; however, significantly more respondents from academic centers reported awareness of services provided by the institution itself (40.2% v 7.8%; P < .001). Significantly more respondents from academic centers reported receiving information relevant to their age group (41.1% v 15.6%; P < .001). Respondents treated at academic centers were significantly more satisfied with support, communication, and overall treatment. Odds of respondents treated at an academic center reporting that their healthcare team knew enough about AYAs were 3.12-fold higher than those treated at community centers (95% CI, 1.6 to 6.4; P = .002). Odds of overall satisfaction were significantly higher for respondents who reported that their healthcare team "knew enough about AYAs" (aOR, 9.7, 95% CI, 2.4 to 53.9; P = .003). CONCLUSION: Cancer treatment for AYAs at both academic and community centers can be optimized by improving healthcare providers' understanding of the key issues facing AYAs with cancer and by increasing AYA-specific institutional resources and support services.

Breast Cancer in Adolescent and Young Adult Women Under the Age of 40 Years.

In the United States, one in 196 women is diagnosed with breast cancer under the age of 40 years. Adolescents and young adults (AYAs), of age 15-39 years at diagnosis, experience a number of unique challenges when confronting breast cancer. The incidence of invasive breast cancer has increased among AYA women in the United States since 2004, and most of this change is due to an increase in young women diagnosed with distant disease. AYAs are more likely than older women to present with aggressive subtypes and advanced disease, and they often require systemic staging at diagnosis. Clinical trials should be considered whenever possible, particularly in AYAs with locally advanced or metastatic disease at diagnosis and those with disease progression or recurrence. A significant proportion of AYAs carry germline cancer predisposition mutations, which necessitates prompt genetic testing for all AYAs at diagnosis and may influence choice of local therapy. Suppression of ovarian function, as an adjunct to chemotherapy, may improve breast cancer survival in AYAs. To provide optimal care for AYAs with breast cancer, clinicians should engage multidisciplinary teams that offer fertility preservation, genetic counseling, physical and occupational therapy, nutrition, and psychosocial support, along with medical expertise in tailoring cancer-directed therapy and symptom management toward young women.

Religious/Spiritual Coping in Young Adults with Cancer.

Purpose: The study used a cross-sectional descriptive design to explore the prevalence and correlates of religious/spiritual (R/S) coping and struggle in young adults (YAs) during the first 2 months of cancer treatment. Methods: Self-report measures of R/S coping, R/S struggle, depression, quality of life (QoL), intensity of treatment experience, and spiritual/religious identification and practices were obtained using REDCap Survey. Self-report of selected demographic characteristics (age, ethnicity, race, gender, education, occupational status, marital status, parental status, and cancer diagnosis) was also obtained. Results: The prevalence of positive R/S coping was high and higher compared with negative R/S coping. Female gender was associated with more R/S struggle, lower QoL, and higher depression. The Religious and Spiritual Struggles Scale and both the negative and positive R/S coping scale of the Brief RCOPE were significantly positively correlated, despite focusing on differing types of spiritual struggle/distress. Conclusions: Both positive R/S coping and R/S struggle occur in YAs during the first 2 months of cancer treatment. Further research to elucidate the experiences of YAs with cancer, and interventions to promote effective coping, will promote holistic cancer care for this population.

Analysis of Melanoma Secretome for Factors That Directly Disrupt the Barrier Integrity of Brain Endothelial Cells.

We have recently demonstrated that invasive melanoma cells are capable of disrupting the brain endothelial barrier integrity. This was shown using ECIS biosensor technology, which revealed rapid disruption via the paracellular junctions. In this paper, we demonstrate that melanoma cells secrete factors (e.g., cytokines) that weaken the endothelial barrier integrity. Through proteome profiling, we attempt to identify the barrier-disrupting cytokines. Melanoma conditioned media were collected from three New Zealand melanoma lines. ECIS technology was used to assess if the conditioned media disrupted the endothelial barrier independent of the melanoma cells. The melanoma cell secretome was assessed using cytometric bead array (CBA), Luminex immunoassay and multiplex Proteome Profilers, to detect the expression of secretory proteins, which may facilitate metastasis. Finally, ECIS technology was used to assess the direct effects of secreted proteins identified as candidates from the proteome screens. We show that melanoma-conditioned media significantly disrupted the brain endothelial barrier, however, to a much lesser extent than the cells from which they were collected. Cytokine and proteome profiling of the conditioned media showed evidence of high concentrations of approximately 15 secreted proteins (including osteopontin, IL-8, GDF-15, MIF and VEGF). These 15 secreted proteins were expressed variably across the melanoma lines. Surprisingly, the addition of these individually to the brain endothelial cells did not substantially affect the barrier integrity. ANGPTL-4 and TGFß were also produced by the melanoma cells. Whilst TGFß-1 had a pronounced effect on the barrier integrity, surprisingly ANGPTL-4 did not. However, its C-terminal fragment did and within a very similar period to the conditioned media, albeit not to the same extent. Herein we show that melanoma cells produce a wide-range of soluble factors at high concentrations, which most likely favour support or survival of the cancer cells. Most of these, except for TGFß-1 and the C-terminal fragment of ANGPTL-4, did not have an impact on the integrity of the brain endothelial cells.

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BACKGROUND: Few adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014). METHODS: Using AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics. RESULTS: Overall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively). CONCLUSION: Not only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed.

"Aftermath": Financial Resource Requirements of Young Adults Moving Forward After Cancer Treatment.

Purpose: Young adults (YAs) are at greater risk for cancer-related financial toxicity than other age groups. They are simultaneously dealing with cancer and normative developmental tasks (establishing independence, completing education, and beginning careers) and may go without needed medications, follow-up, and even food or housing because of cancer-related financial toxicity. This study explored the financial resources required for YAs to move forward after cancer treatment. Methods: To identify and describe the financial challenges experienced by YA cancer survivors and the impact on their lives and overall development, we used secondary analysis of essays written by Samfund grant recipients. Directed content analysis allowed identification of salient categories from the essays of 104 YAs aged 17-39 years who received financial assistance between 2012 and 2013. Permission was secured before analysis. Results: To move forward after cancer treatment, YAs state that they require enough financial resources to meet immediate needs, support future goals, facilitate self-care, and enable normative development. Conclusions: Assessing the financial status of YAs with cancer is vital because many YAs lack resources to fund their basic needs and to move forward with independent living after cancer therapy. Interventions to identify and mitigate financial toxicity in YAs have the potential to reduce treatment nonadherence and poor follow-up due to insufficient financial resources in this at-risk population.

Putting Adolescents and Young Adults in a Room Together: Launching an Adolescent and Young Adult Oncology Council.

Purpose: This article describes the formation and first meeting of a community adolescent and young adult oncology council (AYAOC), which was created to promote patient and stakeholder involvement in research and programmatic initiatives within community-based cancer centers. Methods: The AYAOC (comprising patients/survivors, family members, researchers and clinicians) convened at a one-day workshop moderated by an Australian not-for-profit AYA cancer organization. The council shared and compared health care experiences and then identified and prioritized unmet health care needs. Workshop notes were analyzed using inductive content analysis. Results: AYAOC members identified similarities in their experiences of cancer care and priorities for improvement of the health care system. Peer connection and the creation of adolescent and young adult (AYA)-specific care facilities were identified as the most pressing needs for AYAs with cancer, closely followed by integration of complementary medicine into medical practice and government advocacy to improve the quality and consistency of AYA cancer care delivery. Themes identified from AYAOC discussion included emotional isolation, naivety with and sometimes distrust of the medical system, the lasting impact of cancer on identity, the need for emotionally safe interactions with both individual clinicians and groups of peers, and the desire to take personal action to improve care for future patients. Conclusion: AYAOC members expressed a drive to share their experiences, advocate for others, and improve health care services for the "next generation" of AYAs diagnosed with cancer. Sharing stories and connecting with peers may have personal value for individuals. Channeling the altruistic energy of AYAs and stakeholders into group advisory and advocacy efforts also has value for health care systems, allowing stakeholder insights to inform clinical service delivery and research priorities.

Delay in Treatment After Cancer Diagnosis in Adolescents and Young Adults: Does Facility Transfer Matter?

Background: Timeliness is one of the fundamental yet understudied quality metrics of cancer care. Little is known about cancer treatment delay among adolescent and young adult (AYA) cancer patients. This study assessed cancer treatment delay, with a specific focus on facility transfer and diagnosis/treatment interval. Methods: Based on MultiCare Health System's (MHS's) institutional cancer registry data of AYA patients diagnosed during 2006-2015, this study analyzed patient demographics, insurance, clinical characteristics, and time of diagnosis and treatment initiation. Chi-squared tests, cumulative hazard estimates, and Cox proportional regression were used for univariable analysis. Multivariate regression models were used to test the association between care transfer and days of interval or prolonged delay, controlling for baseline parameters. Results: Of 840 analytic AYA cases identified, 457 (54.5%) were both diagnosed and treated within MHS. A total of 45.5% were either diagnosed or treated elsewhere. Mean and median intervals for treatment initiation were 27.03 (95% CI = 21.94-33.14) and 8.00 days (95% CI = 5.00-11.00), respectively, with significant differences between patients with and without facility transfer. Transfer was significantly correlated with longer length of diagnosis-to-treatment interval. Treatment delay, ≥1 week, was associated with transfer, female sex, older age, no surgery involvement, and more treatment modalities. Treatment delay, ≥4 weeks, was associated with transfer, female sex, no insurance, and no surgery involvement. Conclusion: In a community care setting, the diagnosis-to-treatment interval is significantly longer for transferred AYA cancer patients than for patients without a transfer. Future studies are warranted to explore the prognostic implications and the reasons for delays within specific cancer types.

Modifiable Risk Factors for the Development of Breast Cancer in Young Women.

INTRODUCTION: Breast cancer is the most common malignancy among adolescents and young adults (AYAs) women aged 15 to 39 years at diagnosis. An improved understanding of modifiable factors that mitigate the risks of the development of breast cancer may allow for future strategies to reduce the incidence of AYA breast cancer. METHOD: A literature review was conducted to report upon associations between modifiable lifestyle factors and breast cancer risk. RESULTS: Higher levels of physical activity, lower red meat intake, and higher intake of plants appear to decrease the risk of developing AYA breast cancer, whereas associations between obesity and AYA breast cancer risk were less straightforward. CONCLUSIONS: Further research, ideally in large prospective trials, is needed to truly understand modifiable risk factors for the development of AYA breast cancer.

In Vitro Wounding Models Using the Electric Cell-Substrate Impedance Sensing (ECIS)-Zθ Technology.

Electric Cell-Substrate Impedance Sensing (ECIS) can produce reproducible wounding models by mechanically disrupting a cell monolayer. This study compared in vitro wound-healing using human cerebral microvascular endothelial cells (hCMVEC) with both single electrode (8W1E) and multiple electrodes (8W10E+) arrays. Measurements of hCMVEC migration and barrier functions were conducted, revealing variable levels of barrier disruption could be achieved by altering the duration and magnitude of the applied current. In all scenarios, the barrier (Rb) did not recover the strength observed prior to injury. Localization of junctional proteins following wounding were analyzed by immunocytochemistry. Following wounding, cell migration was generally faster on the 8W10E+ than the 8W1E array. Immunohistochemical analysis revealed non-viable cells remained on the 8W1E electrodes but not the 8W10E+ electrodes. However, viable cells partially remained on the 8W10E+ electrodes following wounding. In addition, the 8W10E+ electrodes demonstrated variation in cell loss across electrodes within the same well. This suggests the type of wounding is different on the two array types. However, our data show both arrays can be used to model incomplete barrier recovery and therefore both have potential for testing of drugs to improve endothelial barrier function. This is the first time that the possibility of using the 8W10E+ array as a wounding model is addressed. We highlight the differences in wounding produced between the two arrays, and can be used to study the underlying causes for impaired barrier function following CNS injuries.

Breast cancer in adolescents and young adults.

Breast cancer is the most common cancer of adolescents and young adult (AYA) women aged 15 to 39 years, accounting for 5.6% of all invasive breast cancer in women. In comparison with older women, AYAs are more likely to have familial cancer predisposition genes, larger breast tumors, unfavorable biological characteristics, distant metastatic disease at diagnosis, and adverse outcome. Endocrine therapy and some chemotherapy recommendations differ between young and older women. AYAs require coordinated multidisciplinary care, treatment regimens that minimize late effects such as premature menopause and osteoporosis, and proactive management of psychological and sexual health during and after cancer treatment.

The Importance of Multifrequency Impedance Sensing of Endothelial Barrier Formation Using ECIS Technology for the Generation of a Strong and Durable Paracellular Barrier.

In this paper, we demonstrate the application of electrical cell-substrate impedance sensing (ECIS) technology for measuring differences in the formation of a strong and durable endothelial barrier model. In addition, we highlight the capacity of ECIS technology to model the parameters of the physical barrier associated with (I) the paracellular space (referred to as Rb) and (II) the basal adhesion of the endothelial cells (α, alpha). Physiologically, both parameters are very important for the correct formation of endothelial barriers. ECIS technology is the only commercially available technology that can measure and model these parameters independently of each other, which is important in the context of ascertaining whether a change in overall barrier resistance (R) occurs because of molecular changes in the paracellular junctional molecules or changes in the basal adhesion molecules. Finally, we show that the temporal changes observed in the paracellular Rb can be associated with changes in specific junctional proteins (CD144, ZO-1, and catenins), which have major roles in governing the overall strength of the junctional communication between neighbouring endothelial cells.

The functional and inflammatory response of brain endothelial cells to Toll-Like Receptor agonists.

Toll-Like receptors (TLRs) represent an important early warning mechanism for the immune system to detect infection or tissue damage. The focus of this research was to determine the neuroinflammatory responses to commercial TLR ligands and their effects on brain endothelial barrier strength. Using biosensor technology we screened TLR ligands to all human TLRs and found that the brain endothelial hCMVECs cell line only responded to Poly(I:C) (TLR3-ligand), LPS (TLR4-ligand) and Imiquimod (TLR7 ligand). Both Poly(I:C) and LPS induced pronounced pro-inflammatory cytokine secretion as expected, whereas Imiquimod did not induce secretion of any pro-inflammatory cytokines. Using ECIS technology to measure endothelial barrier function, LPS and Poly(I:C) both acutely reduced barrier-strength, whereas Imiquimod caused immediate and sustained strengthening of the barrier. Further cytokine and ECIS studies showed that Imiquimod could abrogate some of the pro-inflammatory responses to Poly(I:C) and LPS. Most surprisingly, PCR revealed that the hCMVECs lacked TLR7 but expressed both TLR3 and TLR4 and did not respond to other structurally different TLR7 ligands. These data demonstrate that brain endothelial cells can be regulated by TLR 3 and TLR4 ligands in a pro-inflammatory manner and have receptors to Imiquimod, distinct to the classical TLR7, that function in an anti-inflammatory manner.