Do Common Risk Adjustment Methods Do Their Job Well if Center Effects are Correlated With the Center-Specific Mean Values of Patient Characteristics?

BACKGROUND: Direct and indirect standardization are well-established approaches to performing risk adjustment when comparing outcomes between healthcare providers. However, it is an open question whether they work well when there is an association between the center effects and the distributions of the patient characteristics in these centers. OBJECTIVES AND METHODS: We try to shed further light on the impact of such an association. We construct an artificial case study with a single covariate, in which centers can be classified as performing above, on, or below average, and the center effects correlate with center-specific mean values of a patient characteristic, as a consequence of differential quality improvement. Based on this case study, direct standardization and indirect standardization-based on marginal as well as conditional models-are compared with respect to systematic differences between their results. RESULTS: Systematic differences between the methods were observed. All methods produced results that partially reflect differences in mean age across the centers. This may mask the classification as above, on, or below average. The differences could be explained by an inspection of the parameter estimates in the models fitted. CONCLUSIONS: In case of correlations of center effects with center-specific mean values of a covariate, different risk adjustment methods can produce systematically differing results. This suggests the routine use of sensitivity analyses. Center effects in a conditional model need not reflect the position of a center above or below average, questioning its use in defining the truth. Further empirical investigations are necessary to judge the practical relevance of these findings.

Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC). METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity. RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI. CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

A Novel Methodological Approach to Measure Linear Trends in Health Inequalities: Proof of Concept With Adolescent Smoking in Europe.

We describe a new method for presenting and interpreting linear trends in health inequalities, and present a proof-of-concept analysis of inequalities in smoking among adolescents in Europe. We estimated the regression line of the assumed linear relationship between smoking prevalence in low- and high-socioeconomic status (SES) youth over time. Using simulation, we constructed a 95% confidence interval (CI) for the smoking prevalence in low-SES youth for when this would be 0% in high-SES youth, and we calculated the likelihood of eradicating smoking inequality (<5% for both low and high SES). This method was applied to data on adolescents aged 15-16 years (n = 250,326) from 23 European countries, derived from the 2003-2015 European Survey Project on Alcohol and Other Drugs. Smoking prevalence decreased more slowly among low- than among high-SES adolescents. The estimated smoking prevalence was 9.4% (95% CI: 6.1, 12.7) for boys and 5.4% (95% CI: 1.4, 9.2) for girls with low SES when 0% with high SES. The likelihood of eradicating smoking inequality was <1% for boys and 37% for girls. We conclude that this novel methodological approach to trends in health inequalities is feasible in practice. Applying it to trends in smoking inequalities among adolescents in Europe, we found that Europe is currently not on track to eradicate youth smoking across SES groups.

A2Sign: Agnostic Algorithms for Signatures-a universal method for identifying molecular signatures from transcriptomic datasets prior to cell-type deconvolution.

MOTIVATION: Molecular signatures are critical for inferring the proportions of cell types from bulk transcriptomics data. However, the identification of these signatures is based on a methodology that relies on prior biological knowledge of the cell types being studied. When working with less known biological material, a data-driven approach is required to uncover the underlying classes and generate ad hoc signatures from healthy or pathogenic tissue. RESULTS: We present a new approach, A2Sign: Agnostic Algorithms for Signatures, based on a non-negative tensor factorization (NTF) strategy that allows us to identify cell-type-specific molecular signatures, greatly reduce collinearities and also account for inter-individual variability. We propose a global framework that can be applied to uncover molecular signatures for cell-type deconvolution in arbitrary tissues using bulk transcriptome data. We also present two new molecular signatures for deconvolution of up to 16 immune cell types using microarray or RNA-seq data. AVAILABILITY AND IMPLEMENTATION: All steps of our analysis were implemented in annotated Python notebooks (https://github.com/paulfogel/A2SIGN). To perform NTF, we used the NMTF package, which can be downloaded using Python pip install. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Development and Evaluation of Brief Web-Based Education for Primary Care Providers to Address Inequities in Lung Cancer Screening and Smoking Cessation Treatment.

Annual lung cancer screening (LCS) is recommended for individuals at high risk for lung cancer. However, primary care provider-initiated discussions about LCS and referrals for screening are low overall, particularly among Black or African Americans and other minoritized racial and ethnic groups. Disparities also exist in receiving provider advice to quit smoking. Effective methods are needed to improve provider knowledge about LCS and tobacco-related disparities, and to provide resources to achieve equity in LCS rates. We report the feasibility and impact of pairing a self-directed Lung Cancer Health Disparities (HD) Web-based course with the National Training Network Lung Cancer Screening (LuCa) course on primary care providers' knowledge about LCS and the health disparities associated with LCS. In a quasi-experimental study, primary care providers (N = 91) recruited from the MedStar Health System were assigned to complete the LuCa course only vs. the LuCa + HD courses. We measured pre-post-LCS-related knowledge and opinions about the courses. The majority (60.4%) of providers were resident physicians. There was no significant difference between groups on post-test knowledge (p > 0.05). However, within groups, there was an improvement in knowledge from pre- to post-test (LuCa only (p = 0.03); LuCa + HD (p < 0.001)). The majority of providers (81%) indicated they planned to improve their screening and preventive practices after having reviewed the educational modules. These findings provide preliminary evidence that this e-learning course can be used to educate providers on LCS, smoking cessation, and related disparities impacting patients.

Using Protection Motivation Theory to Predict Intentions for Breast Cancer Risk Management: Intervention Mechanisms from a Randomized Controlled Trial.

The purpose of this study is to evaluate the direct and indirect effects of a web-based, Protection Motivation Theory (PMT)-informed breast cancer education and decision support tool on intentions for risk-reducing medication and breast MRI among high-risk women. Women with ≥ 1.67% 5-year breast cancer risk (N = 995) were randomized to (1) control or (2) the PMT-informed intervention. Six weeks post-intervention, 924 (93% retention) self-reported PMT constructs and behavioral intentions. Bootstrapped mediations evaluated the direct effect of the intervention on behavioral intentions and the mediating role of PMT constructs. There was no direct intervention effect on intentions for risk-reducing medication or MRI (p's ≥ 0.12). There were significant indirect effects on risk-reducing medication intentions via perceived risk, self-efficacy, and response efficacy, and on MRI intentions via perceived risk and response efficacy (p's ≤ 0.04). The PMT-informed intervention effected behavioral intentions via perceived breast cancer risk, self-efficacy, and response efficacy. Future research should extend these findings from intentions to behavior. ClinicalTrials.gov Identifier: NCT03029286 (date of registration: January 24, 2017).

Lung cancer screening use and implications of varying eligibility criteria by race and ethnicity: 2019 Behavioral Risk Factor Surveillance System data.

BACKGROUND: In 2021, the US Preventive Services Task Force (USPSTF) expanded the eligibility criteria for low-dose computed tomographic lung cancer screening (LCS) to reduce racial disparities that resulted from the 2013 USPSTF criteria. The annual LCS rate has risen slowly since the 2013 USPSTF screening recommendations. Using the 2019 Behavioral Risk Factor Surveillance System (BRFSS), this study 1) describes LCS use in 2019, 2) compares the percent eligible for LCS using the 2013 versus 2021 USPSTF criteria, and 3) determines the percent eligible using the more detailed PLCOm2012Race3L risk-prediction model. METHODS: The analysis included 41,544 individuals with a smoking history from states participating in the BRFSS LCS module who were ≥50 years old. RESULTS: Using the 2013 USPSTF criteria, 20.7% (95% confidence interval [CI], 19.0-22.4) of eligible individuals underwent LCS in 2019. The 2013 USPSTF criteria was compared to the 2021 USPSTF criteria, and the overall proportion eligible increased from 21.0% (95% CI, 20.2-21.8) to 34.7% (95 CI, 33.8-35.6). Applying the 2021 criteria, the proportion eligible by race was 35.8% (95% CI, 34.8-36.7) among Whites, 28.5% (95% CI, 25.2-31.9) among Blacks, and 18.0% (95% CI, 12.4-23.7) among Hispanics. Using the 1.0% 6-year threshold that is comparable to the 2021 USPSTF criteria, the PLCOm2012Race3L model selected more individuals overall and by race. CONCLUSIONS: Using data from 20 states and using multiple imputation, higher LCS rates have been reported compared to prior BRFSS data. The 2021 expanded criteria will result in a greater number of screen-eligible individuals. However, risk-based screening that uses additional risk factors may be more inclusive overall and across subgroups. LAY SUMMARY: In 2013, lung cancer screening (lung screening) was recommended for high risk individuals. The annual rate of lung screening has risen slowly, particularly among Black individuals. In part, this racial disparity resulted in expanded 2021 criteria. Survey data was used to: 1) describe the number of people screened in 2019, 2) compare the percent eligible for lung screening using the 2013 versus 2021 guidelines, and 3) determine the percent eligible using more detailed criteria. Lung screening rates increased in 2019, and the 2021 criteria will result in more individuals eligible for screening. Using additional criteria may identify more individuals eligible for lung screening.

Improved motivation and readiness to quit shortly after lung cancer screening: Evidence for a teachable moment.

BACKGROUND: For patients at high risk for lung cancer, screening using low-dose computed tomography (lung cancer screening [LCS]) is recommended. The purpose of this study was to examine whether screening may serve as a teachable moment for smoking-related outcomes. METHODS: In a smoking-cessation trial, participants (N = 843) completed 2 phone interviews before randomization: before LCS (T0) and after LCS (T1). By using logistic and linear regression, the authors examined teachable moment variables (perceived risk, lung cancer worry) and outcomes (readiness, motivation, and cigarettes per day [CPD]). RESULTS: Participants were a mean ± SD age of 63.7 ± 5.9 years, had 47.8 ± 7.1 pack-years of smoking, 35.2% had a high school diploma or General Educational Development (high school equivalency) degree or less, and 42.3% were undergoing their first scan. Between T0 and T1, 25.7% of participants increased readiness to quit, 9.6% decreased readiness, and 64.7% reported no change (P < .001). Motivation to quit increased (P < .05) and CPD decreased between assessments (P < .001), but only 1.3% self-reported quitting. Compared with individuals who reported no lung cancer worry/little worry, extreme worry was associated with readiness to quit in the next 30 days (odds ratio, 1.8; 95% CI, 1.1-3.0) and with higher motivation (b = 0.83; P < .001) at T1. Individuals undergoing a baseline (vs annual) scan were more ready to quit in the next 30 days (odds ratio, 1.8; 95% CI, 1.3-2.5). CONCLUSIONS: During the brief window between registering for LCS and receiving the results, the authors observed that very few participants quit smoking, but a significant proportion improved on readiness and motivation to quit, particularly among individuals who were undergoing their first scan and those who were extremely worried about lung cancer. These results indicate that providing evidence-based tobacco treatment can build upon this teachable moment.

Predictors of Enrollment of Older Smokers in Six Smoking Cessation Trials in the Lung Cancer Screening Setting: The Smoking Cessation at Lung Examination (SCALE) Collaboration.

SIGNIFICANCE: Increased rates of smoking cessation will be essential to maximize the population benefit of low-dose CT screening for lung cancer. The NCI's Smoking Cessation at Lung Examination (SCALE) Collaboration includes eight randomized trials, each assessing evidence-based interventions among smokers undergoing lung cancer screening (LCS). We examined predictors of trial enrollment to improve future outreach efforts for cessation interventions offered to older smokers in this and other clinical settings. METHODS: We included the six SCALE trials that randomized individual participants. We assessed demographics, intervention modalities, LCS site and trial administration characteristics, and reasons for declining. RESULTS: Of 6285 trial- and LCS-eligible individuals, 3897 (62%) declined and 2388 (38%) enrolled. In multivariable logistic regression analyses, Blacks had higher enrollment rates (OR 1.5, 95% CI 1.2,1.8) compared to Whites. Compared to "NRT Only" trials, those approached for "NRT + prescription medication" trials had higher odds of enrollment (OR 6.1, 95% CI 4.7,7.9). Regarding enrollment methods, trials using "Phone + In Person" methods had higher odds of enrollment (OR 1.6, 95% CI 1.2,1.9) compared to trials using "Phone Only" methods. Some of the reasons for declining enrollment included "too busy" (36.6%), "not ready to quit" (8.2%), "not interested in research" (7.7%), and "not interested in the intervention offered" (6.2%). CONCLUSION: Enrolling smokers in cessation interventions in the LCS setting is a major priority that requires multiple enrollment and intervention modalities. Barriers to enrollment provide insights that can be addressed and applied to future cessation interventions to improve implementation in LCS and other clinical settings with older smokers. IMPLICATIONS: We explored enrollment rates and reasons for declining across six smoking cessation trials in the lung cancer screening setting. Offering multiple accrual methods and pharmacotherapy options predicted increased enrollment across trials. Enrollment rates were also greater among Blacks compared to Whites. The findings offer practical information for the implementation of cessation trials and interventions in the lung cancer screening context and other clinical settings, regarding intervention modalities that may be most appealing to older, long-term smokers.

Process evaluation of a culturally targeted video for Latinas at risk of hereditary breast and ovarian cancer.

This paper presents a process evaluation of a culturally targeted narrative video about hereditary breast and ovarian cancer (HBOC) for Latina women at risk for HBOC. Spanish-speaking Latina women at risk for HBOC participated in a single arm study (n = 40). Participants watched the video developed by the authors and responded to surveys. We used mixed methods to assess theoretical constructs that are hypothesized mediators of narrative interventions (i.e., transportation or engagement, identification with characters, emotions) and implementation outcomes (e.g., acceptability). Descriptive statistics summarized theoretical constructs and implementation outcomes. We conducted Mann-Whitney U tests to assess the differences in theoretical and implementation outcomes between participants who were affected versus. unaffected and participants with different levels of education and health literacy. We used the consensual qualitative research framework to analyze qualitative data. Participants' mean age was 47.1 years (SD = 9.48). Most participants were high school graduates or less (62.5%). Acceptability of the video was extremely high (Md = 10.0, IQR = 0.2, scale 1-10). Most (82.5%) suggested video dissemination be through social media. Participants were highly engaged (Md = 5.7, IQR = 1.5, scale 1-7), strongly identified with the main character (Md = 8.7, IQR = 2.6, scale 1-10), and reported experiencing mostly positive emotions (Md = 9.5, IQR = 2.8, scale 1-10). Participants with low health literacy and affected participants reported a significantly higher identification with the main character (p<.05). Qualitative data reinforced the quantitative findings. Women reported gaining knowledge, correcting misconceptions, and feeling empowered. Our culturally targeted video is highly acceptable and targets mechanisms of behavior change for narrative interventions. The video is easily disseminable and can be used as an education tool for patients including affected and unaffected women and patients with different education and health literacy levels. Future studies should test the impact of the video in enhancing genetic counseling and testing uptake.

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study.

BACKGROUND: Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS: The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS: All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention.

Cognitive function prior to systemic therapy and subsequent well-being in older breast cancer survivors: Longitudinal findings from the Thinking and Living with Cancer Study.

OBJECTIVE: To investigate the relationships between self-reported and objectively measured cognitive function prior to systemic therapy and subsequent well-being outcomes over 24 months in older breast cancer survivors. METHODS: Data were from 397 women aged 60 to 98 diagnosed with non-metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010-2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self-reported FACT-Cog scale. Well-being was measured using the FACT-G functional, physical, social, and emotional well-being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed-effects models assessed the relationships between each of baseline APE, LM, and FACT-Cog quartiles with well-being scores over 24 months, adjusted for confounding variables. RESULTS: At baseline, older survivors in the lowest APE, LM, and FACT-Cog score quartiles experienced poorer global well-being than those in the highest quartiles. At 24 months, older survivors tended to improve in well-being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well-being was 80.3 (95% CI: 76.2-84.3) among those in the lowest vs 86.6 (95% CI: 83.1-90.1) in the highest FACT-cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5-11.1). CONCLUSIONS: Among older breast cancer survivors, self-reported, but not objective cognitive impairments, were associated with lower global well-being over the first 2 years of survivorship.

Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype.

BACKGROUND: Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. METHODS: Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. RESULTS: One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE ε4 interaction (P = .001) in which patients with the APOE ε4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE ε4-negative and without sleep disturbances. There was also a sleep disturbance-COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. CONCLUSIONS: Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.

Marketing Influences on Perceptions of Reduced Nicotine Content Cigarettes.

INTRODUCTION: The Food and Drug Administration announced intent to reduce the nicotine content in cigarettes. There is limited evidence on how reduced nicotine content cigarette (RNC) marketing affects product beliefs and use, and research on this is needed to inform regulations. METHODS: In an online experiment, 426 young adult cigarette smokers (aged 18-30 years) were randomized in a 2 (implicit: red package vs. blue package) × 2 (explicit: corrective message vs. no corrective message) design to view an advertisement for previously commercially available RNCs. Outcomes were advertisement content recall, product beliefs, and use intentions. Participants' responses to open-ended assessment of their beliefs about the stimuli were coded to identify prevailing themes. RESULTS: Red packaging and corrective messaging were independently associated with greater advertisement content recall (p = .01 and p = .04, respectively). There were no significant main or interaction effects on product beliefs or use intentions. Controlling for condition, advertisement content recall was significantly associated with less favorable product beliefs (p < .001) and favorable product beliefs were associated with intent to use the product (p < .001). Open-ended responses converged on the finding that respondents were interested in RNCs, but expressed skepticism about effectiveness and value. CONCLUSIONS: Brief exposure to an RNC advertisement with red packaging and corrective messaging were each independently associated with greater advertisement content recall. The results indicate: (1) interest and confusion among young adult smokers regarding RNCs, (2) beliefs about RNCs are influenced by marketing, and (3) beliefs are associated with intention to use RNCs. IMPLICATIONS: Findings from this study demonstrate the importance of advertising effects on beliefs about RNC products and support the need to regulate advertising and labeling alongside product regulation. More detailed study of advertisement features that affect consumers' beliefs about RNCs and how they impact their processing of explicit messaging about product risks will be important to guide regulatory decision-making.

Decision-making processes among men with low-risk prostate cancer: A survey study.

OBJECTIVE: To characterize decision-making processes and outcomes among men expressing early-treatment preferences for low-risk prostate cancer. METHODS: We conducted telephone surveys of men newly diagnosed with low-risk prostate cancer in 2012 to 2014. We analyzed subjects who had discussed prostate cancer treatment with a clinician and expressed a treatment preference. We asked about decision-making processes, including physician discussions, prostate-cancer knowledge, decision-making styles, treatment preference, and decisional conflict. We compared the responses across treatment groups with χ2 or ANOVA. RESULTS: Participants (n = 761) had a median age of 62; 82% were white, 45% had a college education, and 35% had no comorbidities. Surveys were conducted at a median of 25 days (range 9-100) post diagnosis. Overall, 55% preferred active surveillance (AS), 26% preferred surgery, and 19% preferred radiotherapy. Participants reported routinely considering surgery, radiotherapy, and AS. Most were aware of their low-risk status (97%) and the option for AS (96%). However, men preferring active treatment (AT) were often unaware of treatment complications, including sexual dysfunction (23%) and urinary complications (41%). Most men (63%) wanted to make their own decision after considering the doctor's opinion, and about 90% reported being sufficiently involved in the treatment discussion. Men preferring AS had slightly more uncertainty about their decisions than those preferring AT. CONCLUSIONS: Subjects were actively engaged in decision making and considered a range of treatments. However, we found knowledge gaps about treatment complications among those preferring AT and slightly more decisional uncertainty among those preferring AS, suggesting the need for early decision support.

Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance).

PURPOSE: Breast cancer patients aged 65+ ("older") vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality. METHODS: Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting. RESULTS: Patients were 65-91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2-2.4) and 2.4 (95% CI 1.5-4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n-99) was 3.1 (95% CI 1.6-5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality. CONCLUSIONS: Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

PURPOSE: To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). METHODS: Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1-3 years); and late discontinuation (>3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. RESULTS: Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods. CONCLUSIONS: Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis.

Objectives: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA. Methods: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Results: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates. Conclusion: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. Systematic review registration number: PROSPERO CRD42014014842.