Pain Intensity and Pain Interference in Older Adults: Role of Gender, Obesity and High-Sensitivity C-Reactive Protein.

BACKGROUND: Among older adults, pain intensity and pain interference are more common in women than men and associated with obesity and inflammatory markers. OBJECTIVE: We examined whether the obesity and pain relationship is mediated by the high-sensitivity C-reactive protein (hsCRP), a nonspecific marker of systemic inflammation, and whether this relationship differs by sex. METHODS: Items from Medical Outcomes Study Short Form-36 were used to measure pain intensity and pain interference in daily life. Ordinal logistic regression was used to assess the cross-sectional association among body mass index (BMI), hsCRP levels, pain intensity and pain interference using gender-stratified models adjusted for demographic variables. RESULTS: Participants included 667 community-residing adults over the age of 70 years, free of dementia, enrolled in the Einstein Aging Study (EAS). In women (n = 410), pain intensity was associated with obesity [BMI ≥30 vs. normal, odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.43-3.68] and higher hsCRP (OR = 1.28, 95% CI 1.08-1.51). In a model with obesity and hsCRP, both remained significant, but the association between hsCRP and pain intensity was somewhat attenuated. Obesity (OR = 3.04, 95% CI 1.81-5.11) and higher hsCRP levels (OR = 1.30, 95% CI 1.08-1.56) were also independently associated with greater pain interference in women. After adjustment for pain intensity and BMI, hsCRP was no longer associated with pain interference in women. Greater pain intensity and being overweight or obese continued to be significantly associated with pain interference in women. In men (n = 257), obesity and hsCRP were not associated with pain intensity or pain interference. CONCLUSIONS: In women, the relationship between obesity and higher levels of pain intensity or interference may be accounted for by factors related to hsCRP.

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation Therapy and Chemotherapy.

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.

Improving Adjuvant Liver-Directed Treatment Recommendations for Unresectable Hepatocellular Carcinoma: An Artificial Intelligence-Based Decision-Making Tool.

PURPOSE: Liver-directed therapy after transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine learning (ML) model for treatment recommendation in patients previously treated with TACE and select patients who might benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA). METHODS: This retrospective observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008, to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. A feedforward, ML ensemble model provided a treatment recommendation on the basis of pairwise assessments evaluating each potential treatment option and estimated benefit in survival. RESULTS: Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination of TACE and SBRT or TACE and RFA, respectively. The ML model suggested a different consolidative modality in 32.7% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had significant improvement in progression-free survival (hazard ratio 0.5; P = .007). The most important features for model prediction were cause of cirrhosis, stage of disease, and albumin-bilirubin grade (a measure of liver function). CONCLUSION: In this proof-of-concept study, an ensemble ML model was able to provide treatment recommendations for HCC who had undergone prior TACE. Additional treatment in line with model recommendations was associated with significant improvement in progression-free survival, suggesting a potential benefit for ML-guided medical decision making.

Centers with more therapeutic modalities are associated with improved outcomes for patients with hepatocellular carcinoma.

BACKGROUND: Higher facility volume is correlated to better overall survival (OS), but there is little knowledge on the effect of facility treatment modality number on OS in hepatocellular carcinoma (HCC). METHODS: This is a retrospective analysis of data from the National Cancer Database (NCDB) from 2004-2014 on patients with non-metastatic HCC. Treatment modalities assessed were surgical resection, transplantation, ablation, radioembolization, stereotactic body radiation therapy (SBRT), single-agent chemotherapy, and multi-agent chemotherapy. Facilities were dichotomized at the median of the listed treatment modalities. RESULTS: There were a total of 112,512 patients with non-metastatic HCC. Of a total of 1,230 sites, 830 (67.5%) used four or fewer modalities. Average survival for patients treated at facilities using fewer modalities was 12.0 and 23.5 months for those treated at facilities with more modalities [hazard ratio (HR) =0.52, 95% confidence interval (CI): 0.51-0.53, P<0.001]. After adjusting for facility volume, liver function, tumor and patient characteristics and other prognostic factors in a multivariable Cox model, treatment at a multi-modality facility still provided a survival advantage (HR =0.60, 95% CI: 0.52-0.70, P<0.001). This benefit also persisted after propensity score matching. Sensitivity analysis varying the cut point from 2 to 6 modalities for dichotomization showed that the benefit persisted. Subgroup stratified analyses based on stage showed that the benefit in OS was highest for patients with stage I and II (P≤0.002) but was not significant for stage III or IVa. CONCLUSIONS: Institutions that offered more treatment modalities had improved OS for patients with non-metastatic HCC, especially for those with stage I and II.

Evaluation of the Reliability, Validity, and Predictive Validity of the Subscales of the Perceived Stress Scale in Older Adults.

BACKGROUND: The Perceived Stress Scale (PSS) is made up of two subscales but is typically used as a single summary measure. However, research has shown that the two subscales may have differential properties in older adults. OBJECTIVE: To evaluate the internal consistency, test-retest reliability, and the concurrent and predictive validity for development of amnestic mild cognitive impairment (aMCI) of the positively-worded (PSS-PW) and negatively-worded (PSS-NW) subscale scores of the PSS in older adults. METHODS: We recruited community residing older adults free of dementia from the Einstein Aging Study. Reliability of the PSS-PW and PSS-NW was assessed using Cronbach's alpha for internal consistency and intraclass correlation for one year test-retest reliability. Concurrent validity was evaluated by examining the relationship between the PSS subscales and depression, anxiety, neuroticism, and positive and negative affect. Predictive validity was assessed using multivariate Cox regression analyses to examine the relationship between baseline PSS-PW and PSS-NW score and subsequent onset of aMCI. RESULTS: Both PSS-PW and PSS-NW showed adequate internal consistency and retest reliabilities. Both the PSS-PW and PSS-NW were associated with depression, neuroticism, and negative affect. The PSS-NW was uniquely associated with anxiety while the PSS-PW was uniquely associated with positive affect. Only the PSS-PW was associated with a statistically significant increased risk of incident aMCI (HR = 1.27; 95% CI: 1.06-1.51 for every 5-point increase in PSS-PW). CONCLUSIONS: Evaluating the separate effects of the two PSS subscales may reveal more information than simply using a single summation score. Future research should investigate the PSS-PW and PSS-NW as separate subscales.

Positively worded subscale score of the Perceived Stress Scale is associated with cognitive domain function.

OBJECTIVES: To examine the cross-sectional associations of the separate subscales of the Perceived Stress Scale (PSS) and tests measuring cognitive domains in older adults. METHODS: 897 adults over the age of 70 free of amnestic mild cognitive impairment and dementia and enrolled in the Einstein Aging Study made up the study sample. The PSS-14 was used to measure stress. Three cognitive domains (language, episodic memory, and frontal-executive) had previously been found using principle component analysis. Linear regression analyses were used to determine the relationship between the PSS subscales and cognitive domain function. RESULTS: The study sample had a mean age of 79.1 years and 62.8% were female. Bivariate correlations show that the PSS-14 positively worded subscale of the PSS (PSS-PW) was significantly associated with all three cognitive domains (language: r = -0.15, p < 0.001; episodic memory: r = -0.16, p < 0.001; frontal-executive: r = -0.21, p <0.001) while the negatively worded subscale of the PSS (PSS-NW) was not significantly associated with any cognitive domain. In linear regression analyses adjusted for age, white race, gender, years of education, and depressive symptoms, the PSS-PW remained significantly associated with each of the cognitive domains. The PSS-NW was not associated with any cognitive domains in any model. The PSS-14 was significantly associated with language and episodic memory, but not the frontal-executive domain. CONCLUSION: Worse PSS-PW scores are associated with reduced cognitive function in the executive, memory, and language domains in nondemented older adults. The PSS-PW subscale correlated better with cognitive function than the overall PSS-14. Future research should evaluate the temporality of the association and if stress reduction therapies improve cognitive performance.