Symptom burden and quality of life among patient and family caregiver dyads in advanced cancer.

PURPOSE: Symptom management among patients diagnosed with advanced cancer is a high priority in clinical care that often involves the support of a family caregiver. However, limited studies have examined parallel patient and caregiver symptom burden and associations with their own and each other's quality of life (QOL). This study seeks to identify patient and caregiver symptom clusters and investigate associations between identified clusters and demographic, clinical, and psychosocial factors (cognitive appraisals and QOL). METHODS: This study was a secondary analysis of self-reported baseline survey data collected from a randomized clinical trial of 484 adult advanced cancer patients and their caregivers. Latent class analysis and factor analysis were used to identify symptom clusters. Bivariate statistics tested associations between symptom clusters and demographic, clinical, and psychosocial variables. RESULTS: The most prevalent symptom for patients was energy loss/fatigue and for caregivers, mental distress. Low, moderate, and high symptom burden subgroups were identified at the patient, caregiver, and dyad level. Age, gender, race, income, chronic conditions, cancer type, and treatment type were associated with symptom burden subgroups. Higher symptom burden was associated with more negative appraisals of the cancer and caregiving experience, and poorer QOL (physical, social, emotional, functional, and overall QOL). Dyads whose caregivers had more chronic conditions were more likely to be in the high symptom burden subgroup. CONCLUSION: Patient and caregiver symptom burden influence their own and each other's QOL. These findings reinforce the need to approach symptom management from a dyadic perspective.

Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Potentially Preventable Hospitalizations Among Older Adults: 2010-2014.

PURPOSE: We undertook a study to examine national trends in potentially preventable hospitalizations-those for ambulatory care-sensitive conditions that could have been avoided if patients had timely access to primary care-across 3,200 counties and various subpopulations of older adults in the United States. METHODS: We used 2010-2014 Medicare claims data to examine trends in potentially preventable hospitalizations among beneficiaries aged 65 years and older and developed heat maps to examine county-level variation. We used a generalized estimating equation and adjusted the model for demographics, comorbidities, dual eligibility (Medicare and Medicaid), ZIP code-level income, and county-level number of primary care physicians and hospitals. RESULTS: Across the 3,200 study counties, potentially preventable hospitalizations decreased in 327 counties, increased in 123 counties, and did not change in the rest. At the population level, the adjusted rate of potentially preventable hospitalizations declined by 3.45 percentage points from 19.42% (95% CI, 18.4%-20.5%) in 2010 to 15.97% (95% CI, 15.3%-16.6%) in 2014; it declined by 2.93, 2.87, and 3.33 percentage points among White, Black, and Hispanic patients to 14.96% (95% CI, 14.67%-15.24%), 17.92% (95% CI, 17.27%-18.58%), and 17.10% (95% CI, 16.25%-18.0%), respectively. Similarly, the rate for dually eligible patients fell by 3.71 percentage points from 21.62% (95% CI, 20.5%-22.8%) in 2010 to 17.91% (95% CI, 17.2%-18.7%) in 2014. (P <.001 for all). CONCLUSIONS: During 2010-2014, rates of potentially preventable hospitalization did not change in the majority of counties. At the population level, although the rate declined among all subpopulations, dually eligible patients and Black and Hispanic patients continued to have substantially higher rates compared with non-dually eligible and White patients, respectively.

Review and Comparison of Computational Approaches for Joint Longitudinal and Time-to-Event Models.

Joint models for longitudinal and time-to-event data are useful in situations where an association exists between a longitudinal marker and an event time. These models are typically complicated due to the presence of shared random effects and multiple submodels. As a consequence, software implementation is warranted that is not prohibitively time consuming. While methodological research in this area continues, several statistical software procedures exist to assist in the fitting of some joint models. We review the available implementation for frequentist and Bayesian models in the statistical programming languages R, SAS, and Stata. A description of each procedure is given including estimation techniques, input and data requirements, available options for customization, and some available extensions, such as competing risks models. The software implementations are compared and contrasted through extensive simulation, highlighting their strengths and weaknesses. Data from an ongoing trial on adrenal cancer patients is used to study different nuances of software fitting on a practical example.

Genetic Counseling, Testing, and Family Communication Into Survivorship After Diagnosis of Breast Cancer.

PURPOSE: To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS: Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS: A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication (P < .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications (P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively (P < .001). CONCLUSION: Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.

The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014.

INTRODUCTION: Often misperceived as solely a dental disease, periodontitis is a chronic condition characterized by inflammation of the support structures of the tooth and associated with chronic systemic inflammation and endothelial dysfunction. Despite affecting almost 40% of US adults 30 years of age or older, periodontitis is rarely considered when quantifying the multimorbidity (the presence of 2 or more chronic conditions in an individual) burden for our patients. Multimorbidity represents a major challenge for primary care and is associated with increasing health care expenditure and increased hospitalizations. We hypothesized that periodontitis was associated with multimorbidity. METHODS: To interrogate our hypothesis, we performed a secondary data analysis of a population-based cross-sectional survey, the NHANES 2011 to 2014 dataset. The study population included US adults aged 30 years or older who underwent a periodontal examination. Prevalence of periodontitis in individuals with and without multimorbidity was calculated using likelihood estimates and adjusting for confounding variables with logistic regression models. RESULTS: Individuals with multimorbidity were more likely than the general population and individuals without multimorbidity to have periodontitis. However, in adjusted analyses, there was no independent association between periodontitis and multimorbidity. Given the absence of an association, we included periodontitis as a qualifying condition for the diagnosis of multimorbidity. As a result, the prevalence of multimorbidity in US adults 30 years and older increased from 54.1% to 65.8%. DISCUSSION: Periodontitis is a highly prevalent, preventable chronic inflammatory condition. It shares many common risk factors with multimorbidity but was not independently associated with multimorbidity in our study. Further research is required to understand these observations and whether treating periodontitis in patients with multimorbidity may improve health care outcomes.

Increased Nerve Density Adversely Affects Outcome in Oral Cancer.

PURPOSE: Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND. EXPERIMENTAL DESIGN: To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment. RESULTS: Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977. CONCLUSIONS: High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.

Socially Distanced Teaching: Faculty Feedback on Teaching During Telemedicine.

Background: The purpose of our study was to evaluate the perceptions of clinical faculty while working with medical students in a novel setting of virtual care following the COVID-19 pandemic. Activity: A survey of faculty, fellows, and residents was conducted to assess educators' perceptions of virtual teaching before trying it and after 3 months of experience. Results: Perceived effectiveness of teaching students acute care significantly improved as did perceived effectiveness of teaching chronic care. Discussion: We anticipate that continued experience and comfort with virtual platforms would boost this perception further, allowing faculty development to be honed for optimal teaching in this new paradigm. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01685-9.

Telemedicine versus face-to-face delivery of cognitive behavioral therapy for insomnia: a randomized controlled noninferiority trial.

STUDY OBJECTIVES: In a randomized controlled noninferiority trial, we compared face-to-face and telemedicine delivery (via the AASM SleepTM platform) of cognitive-behavioral therapy (CBT) for insomnia for improving insomnia/sleep and daytime functioning at posttreatment and 3-month follow-up. A secondary objective compared the modalities on treatment credibility, satisfaction, and therapeutic alliance. METHODS: A total of 65 adults with chronic insomnia (46 women, 47.2 ± 16.3 years of age) were randomized to 6 sessions of CBT for insomnia delivered individually via AASM SleepTM (n = 33, CBT-TM) or face-to-face (n = 32, CBT-F2F). Participants completed sleep diaries, the Insomnia Severity Index (ISI), and daytime functioning measures at pretreatment, posttreatment, and 3-month follow-up. Treatment credibility, satisfaction, and therapeutic alliance were compared between treatment modalities. The ISI was the primary noninferiority outcome. RESULTS: Based on a noninferiority margin of four points on the ISI and, after adjusting for confounders, CBT-TM was noninferior to CBT-F2F at posttreatment (ß = 0.54, SE = 1.10, 95% CI = 1.64 to 2.72) and follow-up (ß = 0.34, SE = 1.10, 95% CI = 1.83 to 2.53). Daytime functioning measures, except the physical composite scale of the SF-12, were significantly improved at posttreatment and follow-up, with no difference between treatment formats. CBT-TM sessions were, on average, nearly 10 min shorter, yet participant ratings of therapeutic alliance were similar to CBT-F2F. CONCLUSIONS: Telemedicine delivery of CBT for insomnia is not inferior to face-to-face for insomnia severity and yields similar improvements on other sleep and daytime functioning outcomes. Further, telemedicine allows for more efficient treatment delivery while not compromising therapeutic alliance. CLINICAL TRIAL REGISTRATION NUMBER: NCT03293745.

Differences between frequent emergency department users in a secondary rural hospital and a tertiary suburban hospital in central Japan: a prevalence study.

OBJECTIVES: Although frequent emergency department (ED) use is a global issue, little research has been conducted in a country like Japan where universal health insurance is available. The study aims to (1) document the proportion of ED visits that are by frequent users and (2) describe the differences in characteristics of frequent ED users and other ED users including expenditures between a secondary and a tertiary hospital. DESIGN: A prevalence study for a period of 1 year. SETTING: A secondary hospital and a tertiary hospital in central Japan. PARTICIPANTS: All patients who presented to the EDs. PRIMARY OUTCOME MEASURES: We defined frequent ED user as a patient who visited the ED≥5 times/year. The main outcome measures were the proportion of frequent ED users among all ED users and the proportion of healthcare expenditures by the frequent ED users among all ED expenditures. RESULTS: Of 25 231 ED visits over 1 year, 134 frequent ED users accounted for 1043 visits-0.66% of all ED users, comprised 4.1% of all ED visits, and accounted for 1.9% of total healthcare expenditures. Median ED visits per one frequent ED user was 7.9. At the patient level, after adjusting for age, gender and receiving public assistance, older age (OR 1.01, 95% CI: 1.00 to 1.02) and receiving public assistance (OR 7.19, 95% CI 2.87 to 18.07) had an association with frequent ED visits. At the visit-level analysis, evaluation by internal medicine (OR 1.27, 95% CI 1.02 to 1.57), psychiatry (OR 124.69, 95% CI 85.89 to 181.01) and obstetrics/gynaecology (OR 2.77, 95% CI 2.09 to 3.67) were associated with frequent ED visits. CONCLUSION: The proportion of frequent ED users, of total visits, and of expenditures attributable to them-while still in the low end of the distribution of published ranges-are lower in this study from Japan than in reports from many other countries.

Provider Involvement in Care During Initial Cancer Treatment and Patient Preferences for Provider Roles After Initial Treatment.

PURPOSE: Patients report strong preferences regarding which provider-oncologist or primary care provider (PCP)-handles their primary care after initial cancer treatment (eg, other cancer screenings, preventive care, comorbidity management). Little is known about associations between provider involvement during initial cancer treatment and patient preferences for provider roles after initial treatment. METHODS: Women who received a diagnosis of early-stage breast cancer in 2014 to 2015 were identified from the Georgia and Los Angeles County SEER registries and surveyed (N = 2,502; 68% response rate). Women reported the level of their providers' involvement in their care during initial cancer treatment. Associations between level of medical oncologist's participation and PCP's engagement during initial cancer treatment and patient preferences for oncologist led ( v PCP led) other cancer screenings after initial treatment were examined using multivariable logistic regression models. RESULTS: During their initial cancer treatment, 20% of women reported medical oncologists participated substantially in delivering primary care and 66% reported PCPs were highly engaged in their cancer care. Two-thirds (66%) of women preferred medical oncologists to handle other cancer screenings after initial treatment. Women who reported substantial medical oncologist participation in primary care were more likely (adjusted odds ratio, 1.42; 95% CI, 1.05 to 1.91) and those who reported high PCP engagement in cancer care were less likely (adjusted odds ratio, 0.41; 95% CI, 0.31 to 0.53) to prefer oncologist-led other cancer screenings after initial treatment. CONCLUSIONS: Providers' involvement during initial cancer treatment may affect patient preferences regarding provision of follow-up primary care. Clarifying provider roles as early as during cancer treatment may help to better delineate their roles throughout survivorship.

Individual and Population Comparisons of Surgery and Radiotherapy Outcomes in Prostate Cancer Using Bayesian Multistate Models.

Importance: Whether surgery or radiotherapy is the preferred treatment for patients with localized prostate cancer continues to be debated, and randomized clinical trials cannot yet fully address this question. Furthermore, there may be heterogeneity in responses, and the optimal treatment for a patient will depend on his clinical and tumor characteristics. Objectives: To use a unified statistical approach to compare the association of surgery and radiotherapy with both metastatic clinical failure (CF) and survival in localized prostate cancer and to develop an online calculator for individualized, treatment-specific outcome prediction. Design, Setting, and Participants: Cohort study for statistical analysis and development of individualized predictions using Bayesian multistate models that jointly consider both CF and survival and adjust for confounding factors. This study used data from patients treated at the University of Michigan between January 1, 1996, and July 1, 2013, with detailed information on treatment, patient and tumor characteristics, and outcomes. Primary analyses were performed in 2017 and 2018. Participants were a cohort of 4544 patients with localized prostate cancer undergoing primary treatment. Exposures: Radical prostatectomy and external beam radiotherapy. Main Outcomes and Measures: The clinical outcomes were metastatic CF, death after CF, and death from other causes. The adjustment factors were age, prostate gland volume, prostate-specific antigen level, comorbidities, Gleason score, perineural invasion, cT category, race, and treatment year. An online calculator was developed to estimate risks for multiple outcomes for any patient based on 2 treatment choices and on his clinical and tumor characteristics. Results: Among 4544 men (mean [SD] age, 61.2 [8.0] years), 3769 underwent radical prostatectomy, 775 received external beam radiotherapy, 157 (3.5%) had CF, 90 (2.0%) died after CF, and 378 (8.3%) died of other causes. Across all patients, there was no significant difference in risk of CF for surgery vs radiotherapy (hazard ratio, 0.80; 95% CI, 0.52-1.23). However, using multistate models, in some cases individualized predictions resulted in different expected outcomes between surgery and radiotherapy for a given patient. Conclusions and Relevance: In this study, after adjustment for measured confounders, the hazard of CF was similar between treatments on average. However, these data indicate a greater oncologic benefit for some individual patients if treated with surgery and for other patients if treated with radiotherapy. Individualized predictions provide a novel approach to facilitate treatment decision making.

Patient Preferences for Primary Care Provider Roles in Breast Cancer Survivorship Care.

Purpose Prior studies have suggested a need for greater clarity about provider roles in team-based cancer care; however, little is known about patients' preferences regarding which providers handle their care needs after primary cancer treatment. Methods We surveyed women with newly diagnosed stages 0 to II breast cancer who were treated in 2014 and 2015 as reported to the Georgia and Los Angeles SEER registries (N = 2,372; 68% response rate). Patient preferences regarding which provider handles the following care needs after treatment were ascertained: follow-up mammograms, screening for other cancers, general preventive care, and comorbidity management. Associations between patient demographic factors with preferences for provider roles-oncology-directed care versus primary care provider (PCP)-directed care-were assessed by using multivariable logistic regression. Results The majority of women preferred that their PCPs handle general preventive care (79%) and comorbidity care (84%), but a notable minority of women preferred that their oncologists direct this care (21% and 16%, respectively). Minority women-black and Asian versus white-and women with a high school education or less-versus undergraduate college education or more-displayed greater odds of preferring oncology-directed care-versus PCP-directed care-for their general preventive care (black odds ratio [OR], 2.01; 95% CI, 1.43 to 2.82; Asian OR, 1.74; 95% CI, 1.13 to 2.69; high school education or less OR, 1.51; 95% CI, 1.10 to 2.08). Similar variations existed for comorbidity care. Conclusion In this sample, minority women and those with less education more often preferred that oncologists direct certain aspects of their care after breast cancer treatment that are normally delivered by a PCP. Efforts to clarify provider roles in survivorship care to patients may be effective in improving team-based cancer care.