A scoping review evaluating physical and cognitive functional outcomes in cancer survivors treated with chemotherapy: charting progress since the 2018 NCI think tank on cancer and aging phenotypes.

PURPOSE: The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes. METHODS: A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design. RESULTS: The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes. CONCLUSION: Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy.

Information Technology and Telemedicine Services in Community Oncology Practices.

PURPOSE: We described information technology support and use of telemedicine for cancer care and research purposes at community oncology practices within the National Cancer Institute Community Oncology Research Program (NCORP). METHODS: We used data from the NCORP 2017 and 2022 Landscape Assessments. Separate logistic regression models were used to assess factors associated with the use of telemedicine for delivery of cancer care in 2017 and for research purposes in 2022 (cancer care delivery not assessed in 2022). RESULTS: Information was available from 210 and 259 practice groups excluding pediatric-only groups in 2017 and 2022, respectively. In 2017, 30% of practice groups used telemedicine for delivery of cancer care; half of these (15% overall) could use telemedicine for research purposes. In 2022, telemedicine was used for research purposes in 73% of practice groups. In multivariable models, self-identifying as a safety-net hospital was associated with a lower odd of telemedicine use for delivery of cancer care (adjusted odds ratio [AOR], 0.39; 95% CI, 0.17 to 0.93), whereas affiliation with a designated critical access hospital was associated with a higher odd of telemedicine use for delivery of cancer care (AOR, 2.29; 95% CI, 1.10 to 4.76). Having a general survivorship clinic (AOR, 1.92; 95% CI, 1.04 to 3.54) and number of oncology providers (increase per 10 providers; AOR, 1.32; 95% CI, 1.05 to 1.65) were associated with telemedicine use for research purposes. CONCLUSION: Almost one third of NCORP practice groups used telemedicine for cancer care delivery in 2017. In 2022, there is high capacity among NCORP practices (almost three-quarters) to use telemedicine for research purposes, especially among practices with a general survivorship clinic and a greater provider number.

External Validation of Risk Factors for Unplanned Hospitalization in Older Adults With Advanced Cancer Receiving Chemotherapy.

BACKGROUND: Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. METHODS: This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. RESULTS: Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0-3, 4-5, and 6-7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04-2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37-3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59-0.71). CONCLUSIONS: The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers. CLINICALTRIALS: gov identifier: NCT02054741.

The role of self-perceived age in older adults considering adjuvant chemotherapy.

INTRODUCTION: Aging-related concerns can increase the risk of treatment toxicities among older adults considering adjuvant chemotherapy. We previously demonstrated that older adults with cancer who reported feeling older than their chronological age (i.e., self-perceived age) were more likely to have aging-related concerns identified during a geriatric assessment. We explored how decisions about adjuvant chemotherapy vary with or are related to older adults' self-perceived age. MATERIALS AND METHODS: We conducted a secondary analysis of a multi-phased feasibility pilot using semi-structured interviews that were conducted to explore the patient decision-making process for adjuvant chemotherapy. Interviews incorporated questions about chronological and perceived age as factors for decision-making. Patient eligibility for the study included (1) age ≥ 70 years and older, (2) a diagnosis of breast, colon, or lung cancer and considering adjuvant chemotherapy, and (3) able to read size 18 font in English. Interview data were analyzed using constant comparative method. RESULTS: Twenty-one patients were enrolled. The mean chronological age was 78 years (range 71-91). The average perceived age of patients was 57 years (range 21-80). Eleven patients chose to receive treatment while ten patients did not. Aging-related themes illustrated that self-perceived age plays an important role when patients make decisions about adjuvant chemotherapy. More specifically, patients who reported their self-perceived age as younger than their chronological age also reported better perceived health status and chose to receive adjuvant chemotherapy. DISCUSSION: Patients' experiences of aging and self-perceived age may have different implications for decision-making.

The role of social networks in prognostic understanding of older adults with advanced cancer.

OBJECTIVES: Explore how older patients utilize their social networks to inform prognostic understanding. METHODS: In a pilot study of adults (≥65 years old) with advanced cancer, 16 patients completed surveys, social network maps, and semi-structured interviews exploring with whom they preferred to communicate about their illness. Interviews were analyzed using open-coding, and codes were categorized into emergent themes. Social network maps and themes were analyzed via mixed-methods social network analysis (MMSNA). Three case examples with diverse network characteristics and communication patterns were selected for further analysis. RESULTS: Three overarching themes (i.e., prognostic understanding, social support, and therapeutic alliance) revealed that patients' prognostic understanding was strongly influenced by the quality of the social support patients perceived from members of their social networks. Patients demonstrated prognostic understanding when they reported close relationships and open communication with their network members. Case examples revealed some ways that patients sought information and had better sense of their prognosis when they had supportive social networks. CONCLUSION: Findings illustrate how understanding social networks may provide information on how older adults with cancer seek, share, and process prognostic information.

Characterization of older adults with cancer seeking acute emergency department care: A prospective observational study.

INTRODUCTION: Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer. MATERIALS AND METHODS: Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017. RESULTS: Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics. DISCUSSION: We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.

Social Justice and Equity: Why Older Adults With Cancer Belong-A Life Course Perspective.

The population of older adults with cancer in the United States is rapidly increasing, which will have a substantial impact on the oncology and public health workforces across the cancer continuum, from prevention to end of life. Unfortunately, inequities in existing social structures that cause increased psychosocial stressors have led to disparities in the incidence of cancer and the morbidity and mortality of cancer for individuals from marginalized backgrounds. It is imperative that older adults, especially those from historically marginalized backgrounds, be adequately represented in all stages of cancer research to address health inequities. Continued efforts and progress toward achieving social justice and health equity require a deeper commitment to and better understanding of the impact of social determinants of health within the cancer domain. Undoubtedly, a more holistic and integrated view that extends beyond the biologic and genetic factors of health must be adopted for health entities to recognize the critical role of environmental, behavioral, and social determinants in cancer health disparities. Against this backdrop, this paper uses a life course approach to present a multifactorial framework for understanding and addressing cancer disparities in an effort to advance social justice and health equity for racially and ethnically diverse older adults.

Older adults with advanced cancer are selective in sharing and seeking information with social networks.

BACKGROUND: Little is known about how older adults (OA) with advanced cancer interact with social network members (NM), and the nature of communication. This qualitative study aimed to characterize the processes by which OAs with cancer engage with NMs regarding their illness. METHODS: OAs 65 + with advanced cancer and considering treatment (n = 29) and NMs (n = 18) underwent semi-structured interviews asking 1) about their illness understanding; 2) to identify NMs with whom OAs discuss health-related matters; and 3) to describe the content, process, and impact of those illness-related conversations. Three coders analyzed transcribed interviews. Codes were categorized and emergent themes were identified to generate hypotheses. RESULTS: OAs seek NMs with medical backgrounds for cancer-related information and NMs with personal experience of a serious illness for emotional support. Patients characterize geographical location, frequency of communication, and length of NM relationship as factors that influence the nature of support the NM provides. Additionally, differences emerged between OA and NM perspectives on the depth of conversations and decision-making. CONCLUSIONS: A better characterization of how OAs' seek and share information and support may improve medical communication, disease understanding, and support goals-concordant care.

Palliative Care Needs and Clinical Outcomes of Patients with Advanced Cancer in the Emergency Department.

Background: Older adults with cancer use the emergency department (ED) for acute concerns. Objectives: Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED. Design: A planned secondary data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data. Settings/Subjects: Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States. Measurements: Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status. Results: Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% [95% confidence interval; CI 3.0-7.6]; p = 0.005) and hospice (1.3% [95% CI 1.0-3.2]; p = 0.52) care and had a higher 30-day mortality rate (8.3%, [95% CI 6.2-10.4]). Conclusions: Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.

Implementation of Teleophthalmology to Improve Diabetic Retinopathy Surveillance: Qualitative Interview Study of Clinical Staff Informed by Implementation Science Frameworks.

BACKGROUND: The store-and-forward camera-based evaluation of the eye, or teleophthalmology, is an effective way to identify diabetic retinopathy, the leading cause of blindness in the United States, but uptake has been slow. Understanding the barriers to and facilitators of implementing teleophthalmology programs from those actively adopting, running, and sustaining such programs is important for widespread adoption. OBJECTIVE: This study aims to understand the factors that are important in introducing teleophthalmology to improve access to diagnostic eye care for patients with diabetes in primary care clinics by using implementation science. METHODS: This qualitative study in 3 urban, low-income, largely racial and ethnic minority-serving safety-net primary care clinics in Rochester, New York, interviewed nurses and physicians on implementing a teleophthalmology program by using questions informed by the Practical, Robust Implementation and Sustainability Model and the Consolidated Framework for Implementation Research. RESULTS: Primary care nurses operationalizing the program in their clinics saw increased work burden and a lack of self-efficacy as barriers. Continuous training on the teleophthalmology process for nurses, physicians, and administrative staff through in-service and peer training by champions and superusers were identified by interviewees as needs. Facilitators included the perceived convenience for the patient and a perceived educational advantage to the program, as it gave an opportunity for providers to discuss the importance of eye care with patients. Concerns in making and tracking referrals to ophthalmology because of challenges related to care coordination were highlighted. The financial aspects of the program (eg, patient coverage and care provider reimbursement) were unclear to many staff members, influencing adoption and sustainability. CONCLUSIONS: Streamlining processes and workflows, training and assigning adequate staff, effectively coordinating care between primary care and eye care to improve follow-ups, and ensuring financial viability can all help streamline the adoption of teleophthalmology.

Accurate and Automated High-Coverage Identification of Chemically Cross-Linked Peptides with MaxLynx.

Cross-linking combined with mass spectrometry (XL-MS) provides a wealth of information about the three-dimensional (3D) structure of proteins and their interactions. We introduce MaxLynx, a novel computational proteomics workflow for XL-MS integrated into the MaxQuant environment. It is applicable to noncleavable and MS-cleavable cross-linkers. For both, we have generalized the Andromeda peptide database search engine to efficiently identify cross-linked peptides. For noncleavable peptides, we implemented a novel dipeptide Andromeda score, which is the basis for a computationally efficient N-squared search engine. Additionally, partial scores summarize the evidence for the two constituents of the dipeptide individually. A posterior error probability (PEP) based on total and partial scores is used to control false discovery rates (FDRs). For MS-cleavable cross-linkers, a score of signature peaks is combined with the conventional Andromeda score on the cleavage products. The MaxQuant 3D peak detection was improved to ensure more accurate determination of the monoisotopic peak of isotope patterns for heavy molecules, which cross-linked peptides typically are. A wide selection of filtering parameters can replace the manual filtering of identifications, which is often necessary when using other pipelines. On benchmark data sets of synthetic peptides, MaxLynx outperforms all other tested software on data for both types of cross-linkers and on a proteome-wide data set of cross-linked Drosophila melanogaster cell lysate. The workflow also supports ion mobility-enhanced MS data. MaxLynx runs on Windows and Linux, contains an interactive viewer for displaying annotated cross-linked spectra, and is freely available at https://www.maxquant.org/.

Observation unit use among patients with cancer following emergency department visits: Results of a multicenter prospective cohort from CONCERN.

PURPOSE: Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED. METHODS: We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay. RESULTS: Of 1051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6-19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 h. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index. CONCLUSION: In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.

MaxDIA enables library-based and library-free data-independent acquisition proteomics.

MaxDIA is a software platform for analyzing data-independent acquisition (DIA) proteomics data within the MaxQuant software environment. Using spectral libraries, MaxDIA achieves deep proteome coverage with substantially better coefficients of variation in protein quantification than other software. MaxDIA is equipped with accurate false discovery rate (FDR) estimates on both library-to-DIA match and protein levels, including when using whole-proteome predicted spectral libraries. This is the foundation of discovery DIA-hypothesis-free analysis of DIA samples without library and with reliable FDR control. MaxDIA performs three- or four-dimensional feature detection of fragment data, and scoring of matches is augmented by machine learning on the features of an identification. MaxDIA's bootstrap DIA workflow performs multiple rounds of matching with increasing quality of recalibration and stringency of matching to the library. Combining MaxDIA with two new technologies-BoxCar acquisition and trapped ion mobility spectrometry-both lead to deep and accurate proteome quantification.

Contralateral suppression of transient evoked otoacoustic emissions in children with phonological disorder.

BACKGROUND: Perception of acoustic details in the speech signal is important for speech sound development. The medial olivocochlear pathway, a part of the auditory efferent system, plays a role in stimulus-related control of the cochlea. One clinical tool to evaluate the medial olivocochlear activity, which is thought to improve speech perception in noise, is the suppression of otoacoustic emissions. AIMS: This study investigated the suppression of transient evoked otoacoustic emissions in children with phonological disorder in comparison with that in typically developing controls. STUDY DESIGN: Case-control study. METHODS: A total of 23 children with phonological disorder (aged 5-10 years) and 21 age- and sex-matched controls (P > 0.05) participated in the study. Participants had pure-tone thresholds ≤ 15 dB hearing loss and normal middle ear functions. Transient evoked otoacoustic emissions with and without contralateral acoustic stimulation were measured. RESULTS: Although the mean transient evoked otoacoustic emissions suppressions were lower in the group with phonological disorder than in the controls, these differences were not statistically significant (P > 0.05). No left/right ear asymmetry of transient evoked otoacoustic emissions suppression was detected in either of the groups (P > 0.05). CONCLUSION: Children with phonological disorder did not show alterations in medial olivocochlear functioning in the medial olivocochlear activity as measured by the contralateral suppression of transient evoked otoacoustic emissions.

Patient perceived value of teleophthalmology in an urban, low income US population with diabetes.

Dilated eye exams are the standard of care to detect advancing, vision threatening, but often asymptomatic retinopathy in a timely fashion, allowing for vision preserving treatments. Annual exam rates are suboptimal, especially in underserved populations. Although teleophthalmology programs tremendously improve annual exam rates in low income/under resourced settings, widespread adoption is limited. Using a mixed methods approach, three focus groups and individual interviews were conducted for patients with type 2 diabetes (N = 23) who had a teleophthalmology exam or a dilated eye exam. A survey and discussion assessed patients' perspectives and value of teleophthalmology, including willingness to pay (WTP). Financial, transportation, and motivational barriers to obtaining an annual dilated eye exam were identified. Patients greatly valued having primary care (PC) based teleophthalmology for its convenience and ability to detect disease to allow for timely treatment and would recommend such a service. Although their WTP was at least the amount of their usual copay, cost was universally cited as a concern. Having a conveniently offered PC based teleophthalmology exam was valued. Educating patients on the value and costs of having such exams may be helpful to encourage informed discussions on eye care, especially in low income, underserved populations. Our study is among the few to provide insight on the value and perceptions of teleophthalmology in US low income, urban minority populations needed to help increase uptake of this innovation. Using surveys followed by facilitated discussion allowed for richer and more varied responses.

Conceptualizing and Counting Discretionary Utilization in the Final 100 Days of Life: A Scoping Review.

CONTEXT: There has been surprisingly little attention to conceptual and methodological issues that influence the measurement of discretionary utilization at the end of life (DIAL), an indicator of quality care. OBJECTIVE: The objectives of this study were to examine how DIALs have been operationally defined and identify areas where evidence is biased or inadequate to inform practice. METHODS: We conducted a scoping review of the English language literature published from 1/1/04 to 6/30/17. Articles were eligible if they reported data on ≥2 DIALs within 100 days of the deaths of adults aged ≥18 years. We explored the influence of research design on how researchers measure DIALs and whether they examine demographic correlates of DIALs. Other potential biases and influences were explored. RESULTS: We extracted data from 254 articles published in 79 journals covering research conducted in 29 countries, mostly focused on cancer care (69.1%). More than 100 DIALs have been examined. Relatively crude, simple variables (e.g., intensive care unit admissions [56.9% of studies], chemotherapy [50.8%], palliative care [40.0%]) have been studied more frequently than complex variables (e.g., burdensome transitions; 7.3%). We found considerable variation in the assessment of DIALs, illustrating the role of research design, professional norms and disciplinary habit. Variables are typically chosen with little input from the public (including patients or caregivers) and clinicians. Fewer than half of the studies examined age (44.6%), gender (37.3%), race (26.5%), or socioeconomic (18.5%) correlates of DIALs. CONCLUSION: Unwarranted variation in DIAL assessments raises difficult questions concerning how DIALs are defined, by whom, and why. We recommend several strategies for improving DIAL assessments. Improved metrics could be used by the public, patients, caregivers, clinicians, researchers, hospitals, health systems, payers, governments, and others to evaluate and improve end-of-life care.

The PRIDE database and related tools and resources in 2019: improving support for quantification data.

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3 years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas.