Late endocrine diseases in survivors of adolescent and young adult cancer in California: a population-based study.

BACKGROUND: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level. METHODS: We used data from the California Cancer Registry (2006-2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15-39 years) who survived ≥2 years after diagnosis. RESULTS: Among 59,343 AYAs, 10-year cumulative incidence was highest for diabetes (4.7%), hypothyroidism (4.6%), other thyroid (2.2%) and parathyroid disorders (1.6%). Hypothyroidism was most common in Hodgkin lymphoma, leukaemia, breast, and cervical cancer survivors, while diabetes was highest among survivors of leukaemias, non-Hodgkin lymphoma, colorectal, cervical, and breast cancer. In multivariable models, factors associated with increased hazard of endocrinopathies were treatment, advanced stage, public insurance, residence in low/middle socioeconomic neighbourhoods, older age, and non-Hispanic Black or Hispanic race/ethnicity. Haematopoietic cell transplant was associated with most endocrinopathies, while chemotherapy was associated with a higher hazard of ovarian dysfunction and hypothyroidism. CONCLUSIONS: We observed a high burden of endocrinopathies among AYA cancer survivors, which varied by treatment and social factors. Evidence-based survivorship guidelines are needed for surveillance of these diseases.

Patterns of Care Following a Positive Fecal Blood Test for Colorectal Cancer: A Mixed Methods Study.

BACKGROUND/OBJECTIVE: Multilevel barriers to colonoscopy after a positive fecal blood test for colorectal cancer (CRC) are well-documented. A less-explored barrier to appropriate follow-up is repeat fecal testing after a positive test. We investigated this phenomenon using mixed methods. DESIGN: This sequential mixed methods study included quantitative data from a large cohort of patients 50-89 years from four healthcare systems with a positive fecal test 2010-2018 and qualitative data from interviews with physicians and patients. MAIN MEASURES: Logistic regression was used to evaluate whether repeat testing was associated with failure to complete subsequent colonoscopy and to identify factors associated with repeat testing. Interviews were coded and analyzed to explore reasons for repeat testing. KEY RESULTS: A total of 316,443 patients had a positive fecal test. Within 1 year, 76.3% received a colonoscopy without repeat fecal testing, 3% repeated testing and then received a colonoscopy, 4.4% repeated testing without colonoscopy, and 16.3% did nothing. Among repeat testers (7.4% of total cohort, N = 23,312), 59% did not receive a colonoscopy within 1 year. In adjusted models, those with an initial positive test followed by a negative second test were significantly less likely to receive colonoscopy than those with two successive positive tests (OR 0.37, 95% CI 0.35-0.40). Older age (65-75 vs. 50-64 years: OR 1.37, 95% CI 1.33-1.41) and higher comorbidity score (≥ 4 vs. 0: OR 1.75, 95% CI 1.67-1.83) were significantly associated with repeat testing compared to those who received colonoscopy without repeat tests. Qualitative interview data revealed reasons underlying repeat testing, including colonoscopy avoidance, bargaining, and disbelief of positive results. CONCLUSIONS: Among patients in this cohort, 7.4% repeated fecal testing after an initial positive test. Of those, over half did not go on to receive a colonoscopy within 1 year. Efforts to improve CRC screening must address repeat fecal testing after a positive test as a barrier to completing colonoscopy.

Barriers and facilitators to implementation and sustainment of guideline-recommended depression screening for patients with breast cancer in medical oncology: a qualitative study.

OBJECTIVES: Implementation of guideline-recommended depression screening in oncology presents numerous challenges. Implementation strategies that are responsive to local context may be critical elements of adoption and sustainment. We evaluated barriers and facilitators to implementation of a depression screening program for breast cancer patients in a community medical oncology setting as part of a cluster randomized controlled trial. METHODS: Guided by the Consolidated Framework for Implementation Research, we employed qualitative methods to evaluate clinician, administrator, and patient perceptions of the program using semi-structured interviews. We used a team-coding approach for the data; thematic development focused on barriers and facilitators to implementation using a grounded theory approach. The codebook was refined through open discussions of subjectivity and unintentional bias, coding, and memo applications (including emergent coding), and the hierarchical structure and relationships of themes. RESULTS: We conducted 20 interviews with 11 clinicians/administrators and 9 patients. Five major themes emerged: (1) gradual acceptance and support of the intervention and workflow; (2) compatibility with system and personal norms and goals; (3) reinforcement of the value of and need for adaptability; (4) self-efficacy within the nursing team; and (5) importance of identifying accountable front-line staff beyond leadership "champions." CONCLUSIONS: Findings suggest a high degree of acceptability and feasibility due to the selection of appropriate implementation strategies, alignment of norms and goals, and a high degree of workflow adaptability. These findings will be uniquely helpful in generating actionable, real-world knowledge to inform the design, implementation, and sustainment of guideline-recommended depression screening programs in oncology. TRIAL REGISTRATION: ClinicalTrials.gov #NCT02941614.

Effect of a Community-Based Medical Oncology Depression Screening Program on Behavioral Health Referrals Among Patients With Breast Cancer: A Randomized Clinical Trial.

Importance: Implementation of guideline-recommended depression screening in medical oncology remains challenging. Evidence suggests that multicomponent care pathways with algorithm-based referral and management are effective, yet implementation of sustainable programs remains limited and implementation-science guided approaches are understudied. Objective: To evaluate the effectiveness of an implementation-strategy guided depression screening program for patients with breast cancer in a community setting. Design, Setting, and Participants: A pragmatic cluster randomized clinical trial conducted within Kaiser Permanente Southern California (KPSC). The trial included 6 medical centers and 1436 patients diagnosed with new primary breast cancer who had a consultation with medical oncology between October 1, 2017, through September 30, 2018. Patients were followed up through study end date of May 31, 2019. Interventions: Six medical centers in Southern California participated and were randomized 1:1 to tailored implementation strategies (intervention, 3 sites, n = 744 patients) or education-only (control, 3 sites, n = 692 patients) groups. The program consisted of screening with the 9-item Patient Health Questionnaire (PHQ-9) and algorithm-based scoring and referral to behavioral health services based on low, moderate, or high score. Clinical teams at tailored intervention sites received program education, audit, and feedback of performance data and implementation facilitation, and clinical workflows were adapted to suit local context. Education-only controls sites received program education. Main Outcomes and Measures: The primary outcome was percent of eligible patients screened and referred (based on PHQ-9 score) at intervention vs control groups measured at the patient level. Secondary outcomes included outpatient health care utilization for behavioral health, primary care, oncology, urgent care, and emergency department. Results: All 1436 eligible patients were randomized at the center level (mean age, 61.5 years; 99% women; 18% Asian, 17% Black, 26% Hispanic, and 37% White) and were followed up to the end of the study, insurance disenrollment, or death. Groups were similar in demographic and tumor characteristics. For the primary outcome, 7.9% (59 of 744) of patients at tailored sites were referred compared with 0.1% (1 of 692) at education-only sites (difference, 7.8%; 95% CI, 5.8%-9.8%). Referrals to a behavioral health clinician were completed by 44 of 59 patients treated at the intervention sites (75%) intervention sites vs 1 of 1 patient at the education-only sites (100%). In adjusted models patients at tailored sites had significantly fewer outpatient visits in medical oncology (rate ratio, 0.86; 95% CI, 0.86-0.89; P = .001), and no significant difference in utilization of primary care, urgent care, and emergency department visits. Conclusions and Relevance: Among patients with breast cancer treated in community-based oncology practices, tailored strategies for implementation of routine depression screening compared with an education-only control group resulted in a greater proportion of referrals to behavioral care. Further research is needed to understand the clinical benefit and cost-effectiveness of this program. Trial Registration: ClinicalTrials.gov Identifier: NCT02941614.

A Patient Portal-Based Commitment Device to Improve Adherence with Screening for Colorectal Cancer: a Retrospective Observational Study.

BACKGROUND: Despite significant investment in colorectal cancer (CRC) screening, 40% of US adults are not up-to-date. Commitment devices, which are psychologically tailored approaches to enforce health goals, may be an effective method to increase CRC screening. OBJECTIVE: Compare the effectiveness of a commitment device (patient self-ordering fecal immunochemical test (FIT) kits) to standard CRC screening outreach. DESIGN: A retrospective observational study. PARTICIPANTS: Participants were > 49 years and < 75 years, had no history of CRC, and were eligible for CRC screening. INTERVENTION: An electronic screening reminder with an embedded order button allowed participants to order FIT kits directly from a patient portal. Those who used the order button were promptly sent a kit; those who did not were later mailed kits. MAIN MEASURES: Primary outcome was completion of FIT kits. Secondary outcomes included number of days to completion, completion of follow-up for positive results, and CRC diagnosis; we also examined prior use of FIT kit. We used inverse probability of treatment weights to control for pretreatment imbalances. KEY RESULTS: The cohort comprised 176,231 participants: 53% female; median age was 59; 11% were Asian, 21% Hispanic/Latino, 7% black, 51% White, 3% other/mixed race. Approximately 10% (N = 16,918) used the button. Using inverse probability of treatment weights, we found that those who used the button had 3.8 times the odds of completing a kit compared to participants who did not (odds ratio, 3.77; 95% confidence interval, 3.57-3.98). Within the button group, 63% of those eligible completed a FIT kit in the year prior to the button compared to 87% in the year after the button became available (p < 0.0001). CONCLUSION: The ability to self-order screening kits may act as a commitment device that increases CRC screening. Scalable tools leveraging existing patient portals such as this can complement existing CRC outreach strategies.

Patient and Physician Perspectives of Deprescribing Potentially Inappropriate Medications in Older Adults with a History of Falls: a Qualitative Study.

BACKGROUND: High-risk medications pose serious safety risks to older adults, including increasing the risk of falls. Deprescribing potentially inappropriate medications (PIMs) in older adults who have experienced a fall is a key element of fall reduction strategies. However, continued use of PIMs in older adults is common, and clinicians may face substantial deprescribing barriers. OBJECTIVE: Explore patient and clinician experiences with and perceptions of deprescribing PIMs in patients with a history of falls. DESIGN: We led guided patient feedback sessions to explore deprescribing scenarios with patient stakeholders and conducted semi-structured interviews with primary care physicians (PCPs) to explore knowledge and awareness of fall risk guidelines, deprescribing experiences, and barriers and facilitators to deprescribing. PARTICIPANTS: PCPs from Kaiser Permanente Southern California (KPSC) and patient members of the KPSC Regional Patient Advisory Committee. APPROACH: We used maximum variation sampling to identify PCPs with patients who had a fall, then categorized the resulting PIM dispense distribution for those patients into high and low frequency. We analyzed the data using a hybrid deductive-inductive approach. Coders applied initial deductively derived codes to the data, simultaneously using an open-code inductive approach to capture emergent themes. KEY RESULTS: Physicians perceived deprescribing discussions as potentially contentious, even among patients with falls. Physicians reported varying comfort levels with deprescribing strategies: some felt that the conversations might be better suited to others (e.g., pharmacists), while others had well-planned negotiation strategies. Patients reported lack of clarity as to the reasons and goals of deprescribing and poor understanding of the seriousness of falls. CONCLUSIONS: Our study suggests that key barriers to deprescribing include PCP trepidation about raising a contentious topic and insufficient patient awareness of the potential seriousness of falls. Findings suggest the need for multifaceted, multilevel deprescribing approaches with clinician training strategies, patient educational resources, and a focus on building trusting patient-clinician relationships.

Impact of COVID-19 on Cervical Cancer Screening Rates Among Women Aged 21-65 Years in a Large Integrated Health Care System - Southern California, January 1-September 30, 2019, and January 1-September 30, 2020.

On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,† including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.§ Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.¶ Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.

Embedded Research in the Learning Healthcare System: Ongoing Challenges and Recommendations for Researchers, Clinicians, and Health System Leaders.

Embedded research is an innovative means to improve performance in the learning healthcare system (LHS). However, few descriptions of successful embedded research programs have been published. In this perspective, we describe the Care Improvement Research Team, a mature partnership between researchers and clinicians at Kaiser Permanente Southern California. The program supports a core team of researchers and staff with dedicated resources to partner with health system leaders and practicing clinicians, using diverse methods to identify and rectify gaps in clinical practice. For example, recent projects helped clinicians to provide better care by reducing prescribing of unnecessary antibiotics for acute sinusitis and by preventing readmissions among the elderly. Embedded in operational workgroups, the team helps formulate research questions and enhances the rigor and relevance of data collection and analysis. A recent business-case analysis cited savings to the organization of over $10 million. We conclude that embedded research programs can play a key role in fulfilling the promise of the LHS. Program success depends on dedicated funding, robust data systems, and strong relationships between researchers and clinical stakeholders. Embedded researchers must be responsive to health system priorities and timelines, while clinicians should embrace researchers as partners in problem solving.

Use of recommended posttreatment services for adolescent and young adult survivors of Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) is a leading cancer diagnosis for adolescents and young adults (AYAs), with an overall 5-year survival rate of >80%. However, to the authors' knowledge, little is known regarding posttreatment patterns of care. In the current study, the authors characterized the use of guideline-recommended services in a cohort of AYA survivors of HL in Kaiser Permanente Southern California. METHODS: Patients with HL who were diagnosed between ages 15 and 39 years between 2000 and 2010 were identified. The authors calculated the number of patients who received recommended short-term care within 2 years after treatment cessation for those who remained enrolled and alive from 2001 through 2015. Use of recommended late-effects screening for breast cancer and cardiovascular disease was examined. Logistic regression was used to evaluate the association between receipt of recommended care and patient, cancer, and treatment characteristics. RESULTS: A total of 354 patients were identified, with a mean age at the time of diagnosis of 26 years (standard deviation, 6.9 years). Approximately 12% of patients had stage I disease, 59% had stage II disease, 17% had stage III disease, and 13% of patients had stage IV disease. Nearly all patients received chemotherapy (95%), 51% received radiotherapy, and 5% received care from a pediatric oncologist. Overall, approximately 49% of patients received recommended short-term care. Of those patients eligible for cardiovascular screening at 10 years posttreatment (60 patients), 53% received at least 1 screening. Of those patients eligible for breast cancer screening (21 patients), approximately 50% underwent at least 1 screening. Regression results indicated that those patients treated by a pediatric oncologist were >3 times as likely to receive recommended short-term care. CONCLUSIONS: The results of the current study highlight gaps in the delivery of posttreatment care to AYA survivors of HL. By determining areas in need of improvement, these findings can guide the development of tailored interventions with which to improve care.

Follow-up of Abnormal Estimated GFR Results Within a Large Integrated Health Care Delivery System: A Mixed-Methods Study.

BACKGROUND: Timely follow-up of abnormal laboratory results is important for high-quality care. We sought to identify risk factors, facilitators, and barriers to timely follow-up of an abnormal estimated glomerular filtration rate (eGFR) for the diagnosis of chronic kidney disease. STUDY DESIGN: Mixed-methods study: retrospective electronic health record (EHR) analyses, physician interviews. SETTING & PARTICIPANTS: Large integrated health care delivery system. Quantitative analyses included 244,540 patients 21 years or older with incident abnormal eGFRs from January 1, 2010, to December 31, 2015, ordered by 7,164 providers. Qualitative analyses included 15 physician interviews. EXPOSURES: Patient-, physician-, and system-level factors. OUTCOME: Timely follow-up of incident abnormal eGFRs, defined as repeat eGFR obtained within 60 to 150 days, follow-up testing before 60 days that indicated normal kidney function, or diagnosis before 60 days of chronic kidney disease or kidney cancer. ANALYTICAL APPROACH: Multivariable robust Poisson regression models accounting for clustering within provider were used to estimate risk ratios (RRs) and 95% CIs for lack of timely follow-up. Team coding was used to identify themes from physician interviews. RESULTS: 58% of patients lacked timely follow-up of their incident abnormal eGFRs (ie, had a care gap). An abnormal creatinine result flag in the EHR was associated with better follow-up (RR for care gap, 0.65; 95% CI, 0.64-0.66). Patient online portal use and physician panel size were weakly associated with follow-up. Patients seen by providers behind on managing their EHR message box were at higher risk for care gaps. Physician interviews identified system-level (eg, panel size and assistance in managing laboratory results) and provider-level (eg, proficiency using EHR tools) factors that influence laboratory result management. LIMITATIONS: Unable to capture intentional delays in follow-up testing. CONCLUSIONS: Timely follow-up of abnormal results remains challenging in an EHR-based integrated health care delivery system. Strategies improving provider EHR message box management and leveraging health information technology (eg, flagging abnormal eGFR results), making organizational/staffing changes (eg, increasing the role of nurses in managing laboratory results), and boosting patient engagement through better patient portals may improve test follow-up.

Developing innovative models of care for cancer survivors: use of implementation science to guide evaluation of appropriateness and feasibility.

PURPOSE: Limited understanding of factors affecting uptake and outcomes of different cancer survivorship care models hampers implementation of best practices. We conducted a formative evaluation of stakeholder-perceived acceptability and feasibility of an embedded primary care provider (PCP) survivorship care model. METHODS: We identified clinical, operational, and patient stakeholders within Kaiser Permanente Southern California and conducted semi-structured interviews. Analyses were guided by the Consolidated Framework for Implementation Research (CFIR), an integrated framework from the field of implementation science. Deductive thematic categories were derived a priori from CFIR domains; thematic sub-categories were developed inductively. RESULTS: We interviewed 12 stakeholders; multiple themes were identified. Acceptability: oncologists and operational leaders perceived that the model was an acceptable solution to issues of capacity and efficiency with the potential to improve quality; however, several oncologists perceived negative consequences including "[loss of] the joy of medicine." Patients were less enthusiastic, fearing the introduction of "[someone] who doesn't know me." Feasibility: confidence was high that this model can succeed, although there was concern about finding the right PCP and investment in training and staff support. Culture/climate: numerous system-level facilitators were identified, including encouragement of innovation and familiarity with developing new models. CONCLUSIONS: Formative evaluation is a critical pre-implementation process. Acceptability and feasibility for this model were high among oncologists and operational leaders but patients were ambivalent. Keys to successful implementation include training and support of engaged PCPs and a patient transition plan introduced early in the care trajectory.

Understanding Comorbidity Profiles and Their Effect on Treatment and Survival in Patients With Colorectal Cancer.

Background: Patients with colorectal cancer (CRC) commonly present at an older age with multiple comorbid conditions and complex care needs at the time of diagnosis. Clusters of comorbid conditions, or profiles, have not been systematically identified in this patient population. This study aimed to identify clinically distinct comorbidity profiles in a large sample of patients with CRC from an integrated healthcare system, and to examine the effect of comorbidity profiles on treatment and survival. Methods: In this retrospective cohort study, we used latent class analysis (LCA) to identify comorbidity profiles in a sample of 7,803 patients with CRC diagnosed between 2008 and 2013. We identified treatment received from electronic health records and used Cox proportional hazards analysis to examine the effect of comorbidity class on survival. We also examined the effect of comorbidity profile on receipt of guideline-recommended treatment. Results: Median age at diagnosis was 66 years, 52% of patients were male, and 48% were nonwhite. A plurality had stage 0-I disease (42%), with 22% stage II, 22% stage III, and 14% stage IV. More than half (59%) had ≤1 comorbid condition, whereas 19% had ≥4 comorbidities. LCA identified 4 distinct comorbidity classes. Classes were distinguished by the presence or absence of vascular and/or respiratory disease and diabetes with complications, as well as progressively greater Charlson comorbidity index scores. Comorbidity class was independently associated with treatment selection (P<.001) and survival (P<.001). Conclusions: Patients with CRC can be described by 4 distinct comorbidity profiles that are independent predictors of treatment and survival. These results provide insight into how comorbidities cluster within patients with CRC. This work represents a shift away from simple counting of comorbid conditions and toward a more nuanced understanding of how comorbidities cluster within groups of patients with CRC.

Use of posttreatment imaging and biomarkers in survivors of early-stage breast cancer: Inappropriate surveillance or necessary care?

BACKGROUND: Advanced imaging and serum biomarkers are commonly used for surveillance in patients with early-stage breast cancer, despite recommendations against this practice. Incentives to perform such low-value testing may be less prominent in integrated health care delivery systems. The purpose of the current study was to evaluate and compare the use of these services within 2 integrated systems: Kaiser Permanente (KP) and Intermountain Healthcare (IH). The authors also sought to distinguish the indication for testing: diagnostic purposes or routine surveillance. METHODS: Patients with American Joint Committee on Cancer stage 0 to II breast cancer diagnosed between 2009 and 2010 were identified and the use of imaging and biomarker tests over an 18-month period were quantified, starting at 1 year after diagnosis. Chart abstraction was performed on a random sample of patients who received testing to identify the indication for testing. Multivariate regression was used to explore associations with the use of nonrecommended care. RESULTS: A total of 6585 patients were identified; 22% had stage 0 disease, 44% had stage I disease, and 34% had stage II disease. Overall, 24% of patients received at least 1 imaging test (25% at KP vs 22% at IH; P = .009) and 28% of patients received at least 1 biomarker (36% at KP vs 13% at IH; P<.001). Chart abstraction revealed that 84% of imaging tests were performed to evaluate symptoms or signs. Virtually all biomarkers were ordered for routine surveillance. Stage of disease, medical center that provided the services, and provider experience were found to be significantly associated with the use of biomarkers. CONCLUSIONS: Advanced imaging was most often performed for appropriate indications, but biomarkers were used for nonrecommended surveillance. Distinguishing between inappropriate use for surveillance and appropriate diagnostic testing is essential when evaluating adherence to recommendations.

Integrating qualitative research methods into care improvement efforts within a learning health system: addressing antibiotic overuse.

BACKGROUND: Despite reports advocating for integration of research into healthcare delivery, scant literature exists describing how this can be accomplished. Examples highlighting application of qualitative research methods embedded into a healthcare system are particularly needed. This article describes the process and value of embedding qualitative research as the second phase of an explanatory, sequential, mixed methods study to improve antibiotic stewardship for acute sinusitis. METHODS: Purposive sampling of providers for in-depth interviews improved understanding of unwarranted antibiotic prescribing and elicited stakeholder recommendations for improvement. Qualitative data collection, transcription and constant comparative analyses occurred iteratively. RESULTS: Emerging themes and sub-themes identified primary drivers of unwarranted antibiotic prescribing patterns and recommendations for improving practice. These findings informed the design of a health system intervention to improve antibiotic stewardship for acute sinusitis. Core components of the intervention are also described. CONCLUSION: Qualitative research can be effectively applied in learning healthcare systems to elucidate quantitative results and inform improvement efforts.

Post-traumatic stress symptoms in cancer survivors: relationship to the impact of cancer scale and other associated risk factors.

PURPOSE: The purpose of this study was to determine the prevalence of post-traumatic stress symptoms in a sample of cancer survivors and to investigate their association with the impact of cancer, depressive symptoms, and social support. METHODS: We administered a survey to participants in a cancer survivor registry. It included: Post-Traumatic Stress Disorder Checklist-Civilian version (PCL-C), Impact of Cancer Scale (IOC) v.2, and measures of social support, income, and long-term effects of cancer. We performed multivariate analyses to estimate associations between PCL-C and other variables. PCL-C score was examined as a continuous dependent variable and categorically. RESULTS: Responses were available from 162 cancer survivors. Mean age was 51 years (standard deviation (SD) 16); mean time since diagnosis was 11 years (SD 10). Mean PCL-C score was 27 (SD 9, range 17-64); 29% of the sample scored 30 and above, 13% scored 38 and above, 7% scored 44 and above. Linear regression indicated that PCL-C scores were significantly associated with the IOC negative impact summary scale (NIS) (p < 0.001), depressive symptoms (p = 0.003), less social support (p = 0.02), and lower income (p = 0.03). NIS subscale analyses showed that two subscales, life interference (LI) and worry (W), were significantly correlated with PCL-C score (LI: p < 0.001; W: p = 0.02). CONCLUSIONS: In this study, the IOC NIS was associated with endorsement of PTSD symptoms. Assessing survivors for PTSD symptoms with the PCL-C could detect those individuals in need of psychosocial support. The IOC may be useful for identifying target areas for interventions to reduce these symptoms among cancer survivors.

Hot alkaline lysis gDNA extraction from formalin-fixed archival tissues.

Formalin fixation of natural history specimens and histopathological material has historically been viewed as an impediment to successful genomic analysis. However, the development of extraction methods specifically tailored to contend with heavily crosslinked archival tissues, re-contextualises millions of previously overlooked specimens as viable molecular assets. Here, we present an easy-to-follow protocol for screening archival wet specimens for molecular viability and subsequent genomic DNA extraction suitable for sequencing. The protocol begins with non-destructive assessment of specimen degradation and preservation media conditions to allow both museum curators and researchers to select specimens most likely to yield an acceptable proportion (20-60%) of mappable endogenous DNA during short-read DNA sequencing. The extraction protocol uses hot alkaline lysis in buffer (0.1M NaOH, 1% SDS, pH 13) to simultaneously lyse and de-crosslink the tissue. To maximise DNA recovery, phenol:chloroform extraction is coupled with a small-fragment optimised SPRI bead clean up. Applied to well-preserved archival tissues, the protocol can yield 1-2 µg DNA per 50 mg of tissue with mean fragment sizes typically ranging from 50-150 bp, which is suitable to recover genomic DNA sufficient to reconstruct complete mitochondrial genomes and achieve up to 25X nuclear genome coverage. We provide guidance for read mapping to a reference genome and discuss the limitations of relying on small fragments for SNP genotyping and de novo genome assembly. This protocol opens the door to broader-scale genetic and phylogenetic analysis of historical specimens, contributing to a deeper understanding of evolutionary trends and adaptation in response to changing environments.

Unsatisfactory Fecal Immunochemical Tests for Colorectal Cancer Screening: Prevalence, Reasons, and Subsequent Testing.

BACKGROUND: Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling. METHODS: Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within 15 months of the unsatisfactory FIT. RESULTS: Of 56,980 individuals completing an index FIT, 10.2% had an unsatisfactory FIT. Reasons included inadequate specimen (51%), incomplete labeling (27%), old specimen (13%), and broken/leaking container (8%). Unsatisfactory FIT was associated with being male [OR, 1.10; confidence interval (CI), 1.03-1.16], Black (OR, 1.46; CI, 1.33-1.61), Spanish speaking (OR, 1.12; CI, 1.01-1.24), on Medicaid (OR, 1.42; CI, 1.28-1.58), and received FIT by mail (OR, 2.66; CI, 2.35-3.01). Among those with an unsatisfactory FIT, fewer than half (41%) completed a subsequent test within 15 months (median, 4.4 months). Adults aged 50-54 years (OR, 1.16; CI, 1.01-1.39) and those who received FIT by mail (OR, 1.92; CI, 1.49-2.09) were more likely to complete a subsequent test. CONCLUSIONS: One in ten returned a FIT that could not be processed, mostly due to patient-related reasons. Fewer than half completed a subsequent test after unsatisfactory FIT. IMPACT: Screening programs should address these breakdowns such as specimen collection and labeling to improve real-world effectiveness. See related In the Spotlight, p. 183.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Emergency Department Use in Adolescent and Young Adult Cancer Early Survivors from 2006 to 2020.

Purpose: Understanding emergency department (ED) use in adolescent and young adult (AYA) survivors could identify gaps in AYA survivorship. Methods: We conducted a cohort study of 7925 AYA survivors (aged 15-39 years at diagnosis) who were 2-5 years from diagnosis in 2006-2020 at Kaiser Permanente Southern California. We calculated ED utilization rates overall and by indication of the encounter (headache, cardiac issues, and suicide attempts). We estimated rate changes by survivorship year and patient factors associated with ED visit using a Poisson model. Results: Cohort was 65.4% women, 45.8% Hispanic, with mean age at diagnosis at 31.3 years. Overall, 38% of AYA survivors had ≥1 ED visit (95th percentile: 5 ED visits). Unadjusted ED rates declined from 374.2/1000 person-years (PY) in Y2 to 327.2 in Y5 (p change < 0.001). Unadjusted rates declined for headache, cardiac issues, and suicide attempts. Factors associated with increased ED use included: age 20-24 at diagnosis [relative risk (RR) = 1.30, 95% CI 1.09-1.56 vs. 35-39 years]; female (RR = 1.27, 95% CI 1.11-1.47 vs. male); non-Hispanic Black race/ethnicity (RR 1.64, 95% CI 1.38-1.95 vs. non-Hispanic white); comorbidity (RR = 1.34, 95% CI 1.16-1.55 for 1 and RR 1.80, 95% CI 1.40-2.30 for 2+ vs. none); and public insurance (RR = 1.99, 95% CI 1.70-2.32 vs. private). Compared with thyroid cancer, cancers associated with increased ED use were breast (RR = 1.45, 95% CI 1.24-1.70), cervical (RR = 2.18, 95% CI 1.76-2.71), colorectal (RR = 2.34, 95% CI 1.94-2.81), and sarcoma (RR = 1.39, 95% CI 1.03-1.88). Conclusion: ED utilization declined as time from diagnosis elapsed, but higher utilization was associated with social determinants of health and cancer types.