The association between social vulnerability and geriatric assessment impairments among older adults with gastrointestinal cancers-The CARE Registry.

BACKGROUND: Older adults comprise the majority of patients with gastrointestinal (GI) cancer. Geriatric assessments (GAs) are recommended for older adults with cancer in part to detect aging-related impairments (e.g., frailty) associated with early mortality. Social factors like social vulnerability may also influence aging-related impairments. However, the association between social vulnerability and aging outcomes among older adults with cancer is understudied. METHODS: The authors included 908 older adults aged 60 years and older who were recently diagnosed with GI cancer undergoing GA at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. The primary exposure of interest was the social vulnerability index (SVI). Outcomes were frailty (frail vs. robust/prefrail) and total number of GA impairments (range, 0-13). The authors examined the association between SVI and outcomes using Poisson regression with robust variance estimation and generalized estimating equations. RESULTS: The median age at GA was 69 years (interquartile range, 64-75 years), 58.2% of patients were male, 22.6% were non-Hispanic Black, 29.1% had colorectal cancer, 28.2% had pancreatic cancer, and 70.3% had stage III/IV disease. Adjusting for age, sex, cancer type, and disease stage, each decile increase in the SVI was associated with an 8% higher prevalence of frailty (prevalence ratio, 1.08; 95% confidence interval, 1.05-1.11) and a 4% higher average count of total GA impairments (risk ratio, 1.04; 95% confidence interval, 1.02-1.06). The results were attenuated after further adjustment for race and education. CONCLUSIONS: Greater social vulnerability was associated with a higher prevalence of frailty and an increasing average number of GA impairments among older adults with GI cancers before systemic treatment. Intervening on social vulnerability may be a target for improving the risk of frailty and GA impairments, but associations of race and education should be further evaluated.

Racial differences in body composition and survival among older adults with gastrointestinal malignancies.

INTRODUCTION: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies. MATERIALS AND METHODS: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification. RESULTS: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm2/m2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival. DISCUSSION: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival.

Comorbid Dementia and Cancer Therapy Decision-Making: A Scoping Review.

Comorbid dementia complicates cancer therapy decision-making in older adults. We aimed to synthesize the recent literature (<5 years) on the challenges associated with cancer therapy decision-making among older people living with dementia (PLWD) and their caregivers. Of the 20,763 references, 8767 had their title and abstract screened, and eight met the inclusion criteria. Six studies were qualitative, one study employed mixed methods, and one study was quasi-experimental. Most studies were conducted in the UK (89%) and reported homogeneity in race and geography. Breast (56%) and prostate (45%) were the most frequent reported cancers. Five studies (56%) reported multiple types of dementia, with two (22%) indicating stages. The studies indicated that communication between patients, caregivers, and clinical teams might alleviate stress caused by worsening health prospects and potential ethical concerns. Information from this review can lead to better-informed, patient-centered treatment decision processes among older PLWD and cancer, their caregivers, and clinicians.

The association between food access and frailty among older adults with gastrointestinal malignancies-The CARE Registry.

BACKGROUND: Food access is associated with higher gastrointestinal (GI) cancer mortality; however, its association with frailty, which is a predictor of premature mortality among older adults with cancer, is less understood. METHODS: The authors included 880 adults aged 60 years and older who were recently diagnosed with GI cancers and were undergoing self-reported geriatric assessment at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. Food access was measured using the 2019 US Department of Agriculture Economic Research Service designation low-income, low-access (LILA), classifying census tracts based on income and/or access to food stores at various distances. The primary outcome was frailty on the CARE (Cancer and Aging Resilience Evaluation) Frailty Index, a composite of the proportion of impaired geriatric assessment measures. The authors examined the LILA-frailty association with modified Poisson regression accounting for census-tract clustering. RESULTS: The median patient age was 69 years, 58.1% were men, 22.5% were non-Hispanic Black, 29.2% had colorectal cancer, 28.0% had pancreatic cancer, 70.1% presented with stage III/IV disease, and 34.9% were frail. A higher proportion in LILA areas were non-Hispanic Black (44.1% vs. 10.8%; p < .001) and had less education (high school or less: 48.1% vs. 37.9%; p = .020). Adjusting for age, race and ethnicity, sex, cancer type and stage, and education, an LILA designation was associated with 58% greater odds of worsening frailty status (95% confidence interval, 1.18-2.12). An analysis of LILA subcategories revealed that associations were maintained across all LILA measures. CONCLUSIONS: Poor food access was associated with a greater risk of frailty among newly diagnosed older adults with GI cancers before they received systemic treatment. Intervening on local food access, particularly in LILA areas, may be a target for improving rates of frailty and promoting health equity in this population.

Management of Older Adults With Colorectal Cancer: The Role of Geriatric Assessment.

Older adults share a growing burden of cancer morbidity and mortality. This is present across the spectrum of oncologic diagnoses and is particularly true with colorectal cancer (CRC), where older adults continue to share the burden of diagnoses. However, optimal cancer treatment decision making in older adults remains a significant challenge, as the majority of previous clinical trials shaping the current treatment landscape have focused on younger patients, often with more robust performance status and fewer medical comorbid conditions. The heterogeneous aging process of older adults with CRC necessitates a personalized treatment approach, as approximately three-quarters of older adults with CRC also have a concominant geriatric syndrome and more than half of older adults with CRC are pre-frail or frail. Treatment decisions shoud be multifaceted, including consultation with the patient and their familes regarding their wishes, with consideration of the patient's quality of life, functional status, medical comorbid conditions, social support, and treatment toxicity risk. Geriatric assessment is a systematic and validated approach to assess an older adults's potential strengths and vulnerabilities, which can in turn be used to assist with comprehensive cancer care planning and support. In this review, we will summarize current treatment approaches for older adults with CRC, with a particular focus on the incorporation of the geriatric assessment.

Anxiety is Associated With Geriatric Assessment Impairments and Reduced Quality of Life Among Older Adults With Colorectal Cancer: Results From the CARE Registry.

BACKGROUND: Colorectal cancer (CRC) preferentially affects older adults. Modifiable factors, such as anxiety, can be measured as part of cancer-specific geriatric assessments (GA) completed prior to the start of treatment. We hypothesized that anxiety is prevalent among older adults with CRC and is associated with increased depression, increased frailty, and impaired health-related quality of life (HRQOL). PATIENTS AND METHODS: Patients ≥60 years old with newly diagnosed CRC completed a cancer-specific GA called the Cancer and Aging Resilience Evaluation (CARE). Between September 2017 and February 2023, we analyzed patients with CRC who had not yet received any systemic treatment. Anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4-item short form and reported as t-scores. We used modified Poisson models with robust variance estimation to assess for differences in the prevalence of depression, frailty, and impaired HRQOL. RESULTS: We analyzed 277 older adults with CRC. The median age of the study sample was 68 years. 57% were male, 72% were non-Hispanic White, and most had advanced CRC (35% stage III and 39% stage IV). Moderate/severe anxiety was present in 17% of older adults with newly diagnosed CRC. In adjusted models, as compared to patients without moderate/severe anxiety, patients with moderate/severe anxiety had significantly increased risk of depression (prevalence ratio [PR] 7.60, CI 4.90-11.78), frailty (PR 4.93, CI 3.01-8.07), impaired physical HRQOL (PR 3.57, CI 2.03-6.28), and impaired mental HRQOL (PR 3.82, CI 2.12-6.89). CONCLUSION: Among older adults with CRC, anxiety is associated with increased depression and frailty as well as reduced HRQOL.

Association of emotional support with quality of life, mental health, and survival in older adults with gastrointestinal malignancies-Results from the CARE registry.

BACKGROUND: Emotional support (ES) is the most frequently reported support need among older adults with cancer. Yet, the association of ES with cancer outcomes is largely unknown. This study examined the association of ES with health-related quality of life (HRQoL), mental health, and survival among older adults with gastrointestinal (GI) malignancies. METHODS: We included newly diagnosed older adults (≥60 years) with GI cancer undergoing self-reported geriatric assessment at their first clinic visit. ES was measured using an adaptation of the Medical Outcomes Study (dichotomized adequate ES vs. inadequate ES). Outcomes included physical and mental HRQoL, anxiety, depression, and survival. Multivariable linear regression evaluated the association between ES and HRQoL scores. Multivariable logistic regression evaluated the association of ES with anxiety and depression. All models were adjusted for age at geriatric assessments, race, sex, and cancer type/stage. RESULTS: 795 participants were included. Median patient age was 68 years (IQR: 64-74), 58% were male, and most cancers were either colorectal (37.9%) or pancreatic (30.8%). Most (77.6%) had adequate ES. Patients with inadequate ES were more likely to be Black (31.5 vs. 20.8%, p = 0.005), disabled (24.1 vs. 10.4%, p < 0.001), widowed/divorced (54.2 vs. 24.8%, p < 0.001) and had lower physical and mental HRQoL t-scores (Physical ß: -3.35, 95% CI: -5.25, -1.46; Mental ß: -2.46, 95% CI: -4.11, -0.81) and higher odds of depression (aOR: 2.22, CI: 1.34-3.69). This study found no difference between those with adequate ES versus inadequate ES in the proportion of deaths within 1 year of diagnosis (24.3% vs. 24.2%, p = 0.966), or within 2 years of diagnosis (32.4% vs. 33.2%, p = 0.126). CONCLUSIONS: Older adults with inadequate ES have worse physical and mental HRQoL and higher odds of depression compared to those with adequate ES.

Rural-urban disparities in mortality and geriatric assessment among older adults with cancer: The cancer & aging resilience evaluation (CARE) registry.

INTRODUCTION: Rural-urban disparities persist in cancer mortality, despite improvement in cancer screening and treatment. Although older adults represent the majority of cancer cases and are over-represented in rural areas, few studies have explored rural-urban disparities in mortality and age-related impairments among older adults with cancer. MATERIALS AND METHODS: We included 962 newly-diagnosed older adults (≥60 years) with cancer who underwent geriatric assessment (GA) at their first pre-chemotherapy visit to an academic medical center in the Southeastern United States. We used Rural-Urban Commuting Area (RUCA) codes to classify residence at time of diagnosis into urban and rural areas. We used one-year survival and pre-treatment frailty as outcomes. We used Cox proportional hazards regression to evaluate the association between residence and one-year mortality, and logistic regression to evaluate the association between residence and pre-treatment frailty. All tests were two-sided. RESULTS: Median age at GA was 68.0 (interquartile rage [IQR]: 64.0, 74.0) years; most had colorectal cancer (24.3%) with advanced stage (III/IV 73.2%) disease. Overall, 11.4% resided in rural and 88.6% in urban areas. Rural areas had a higher proportion of White and less educated participants. After adjustment for age, sex, race, education, employment status, and cancer type/stage, rural residence was associated with higher hazard of one-year mortality (hazard ratio [HR] = 1.78, 95% confidence interval [CI] = 1.23, 2.57) compared to urban residence. Frailty was an effect modifier of this association (HROverall = 1.83, 95% CI = 1.27, 2.57; HRFrail = 2.05, 95% CI = 1.23, 3.41; HRNot Frail = 1.55, 95% CI = 0.90, 2.68). DISCUSSION: Among older adults with newly diagnosed cancer, rural residence was associated with reduced one-year survival, particularly among frail older adults. The rural-urban disparities observed in the current study may be due to frailty in conjunction with disparities in social determinants of health across rural and urban areas. Future studies should focus on understanding and intervening on underlying causes of these disparities.

Hospital-associated disability due to avoidable hospitalizations among older adults.

BACKGROUND: Hospital-associated disability (HAD) is a common complication during the course of acute care hospitalizations in older adults. Many admissions are for ambulatory care sensitive conditions (ACSCs), considered potentially avoidable hospitalizations-conditions that might be treated in outpatient settings to prevent hospitalization and HAD. We compared the incidence of HAD between older adults hospitalized for ACSCs versus those hospitalized for other diagnoses. METHODS: We conducted a retrospective cohort study in inpatient (non-ICU) medical and surgical units of a large southeastern regional academic medical center. Participants were 38,960 older adults ≥ 65 years of age admitted from January 1, 2015, to December 31, 2019. The primary outcome was HAD, defined as decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We used generalized linear mixed models to examine differences in HAD between hospitalizations with a primary diagnosis for an ACSC using standard definitions versus primary diagnosis for other conditions, adjusting for covariates and repeated observations for individuals with multiple hospitalizations. RESULTS: We found that 10% of older adults were admitted for an ACSC, with rates of HAD in those admitted for ACSCs lower than those admitted for other conditions (16% vs. 20.7%, p < 0.001). Age, comorbidity, admission functional status, and admission cognitive impairment were significant predictors for development of HAD. ACSC admissions to medical and medical/surgical services had lower odds of HAD compared with admissions for other conditions, with no significant differences between ACSC and non-ACSC admissions to surgical services. CONCLUSIONS: Rates of HAD among older adults hospitalized for ACSCs are substantial, though lower than rates of HAD with hospitalization for other conditions, reflecting that acute care hospitalization is not a benign event in this population. Treatment of ACSCs in the outpatient setting could be an important component of efforts to reduce HAD.

Differences in Pretreatment Frailty Across Gastrointestinal Cancers in Older Adults: Results From the Cancer and Aging Resilience Evaluation Registry.

PURPOSE: Frailty predicts poor outcomes in older adults with cancer, but how it differs between different cancer types is unknown. We examined differences in pretreatment frailty between colorectal (CRC), pancreatic, and hepatobiliary cancers. METHODS: We included older adults age 60 years or older with the above cancer types enrolled in the Cancer and Aging Resilience Evaluation registry. Frailty was defined using a 44-item Cancer and Aging Resilience Evaluation frailty index constructed on the basis of the principles of deficit accumulation (including several geriatric assessment impairments encompassing malnutrition, functional status, comorbidities, anxiety, depression, cognitive complaints, health-related quality of life, falls, ability to walk one block, interference in social activities, and polypharmacy). Multivariable logistic regression models were used to examine the adjusted odds ratio (aOR) of frailty between cancer types. RESULTS: A total of 505 patients were included (mean age 70 years, 59% male): 211 (41.8%) CRC, 178 (35.2%)pancreatic cancer, and 116 (23.0%) hepatobiliary cancer. Patients with pancreatic cancer had the highest prevalence of frailty (23.3% CRC, 40.6% pancreatic, 34.3% hepatobiliary; P = .001). Both pancreatic (aOR, 2.18; 95% CI, 1.38 to 3.45), and hepatobiliary cancer (aOR, 1.73; 95% CI, 1.03 to 2.93) were independently associated with higher odds of frailty relative to CRC. Frailty was driven by higher rates of malnutrition and instrumental activities of daily living impairments in patients with pancreatic cancer and higher number of comorbidities in patients with hepatobiliary cancer. CONCLUSION: Older adults with pancreatic and hepatobiliary cancers are at high-risk of pretreatment frailty. Early interventions to improve nutritional and functional status and optimization of comorbidities may help improve outcomes.

Longitudinal changes in patient-reported cognitive complaints among older adults with gastrointestinal malignancies - results from the Cancer and Aging Resilience Evaluation (CARE) Registry.

PURPOSE: Longitudinal change in patient-reported cognitive complaints (CC) in older adults with cancer is poorly understood. The purpose of this study was to evaluate early longitudinal CC and predictors among older adults with cancer. METHODS: We examined early CC change on the PROMIS® Short Form4a Cognitive Function among adults ≥ 60 years with GI cancer enrolled in the Cancer and Aging Resilience Evaluation (CARE) undergoing geriatric assessment (GA) at baseline and one 3-6-month follow-up. Multivariable linear regression examined associations of demographics, socioeconomics, GA domains, baseline cognitive score, and treatment toxicities on follow-up cognitive score. Bayesian analysis of covariance (ANCOVA) determined best fitting model. RESULTS: A total of 218 participants were included. The median follow-up was 3.7 months, the mean age was 69.2 ± 7.1, and 57.3% were male. The most common cancer was colorectal (30.7%) with most stage III/IV (73.7%). About half (51.8%) had stable cognition baseline to follow-up (follow-up t-score ± 5 points of baseline), 20.6% improved (≥ 5 increase), and 27.5% declined (≥ 5 decrease). After adjustment, there were no significant baseline predictors of follow-up cognitive t-score. Baseline t-score was the best-fitting predictor of follow-up t-score. CONCLUSIONS: In this first study, examining early change in CC among older adults with cancer, ~ 28% exhibited cognitive decline. Baseline cognition is the most important early predictor of follow-up cognition. Longer follow-up is needed to identify long-term predictors of CC change in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Cognitive decline, even early, may occur in many older adults with cancer. Baseline and regular follow-up assessments of cognitive symptoms are an important component of survivorship care.

The Relationship Between Prior Cancer Diagnosis and All-Cause Dementia Progression Among US Adults.

BACKGROUND: Cancer-related cognitive impairment (CRCI), a frequent effect of cancer and its treatments, shares common cognitive symptoms with dementia syndromes. Cross-sectional studies demonstrate an inverse relationship between cancer and dementia. However, the longitudinal relationship between dementia decline and cancer has not been investigated. OBJECTIVE: To evaluate the association between cancer and longitudinal progression of dementia. METHODS: We extracted electronic health record data from July 2003 to February 2020 from a single academic medical center. We identified dementia and cancer history prior to dementia using ICD-9/10 codes. We measured cognitive decline with the Alabama Brief Cognitive Screener (ABCs). We used adjusted linear mixed models to estimate baseline cognition and rate of progression by cancer history, including differences by race. RESULTS: The study included 3,809 participants with dementia, of which 672 (17.6%) had cancer history. Those with cancer history had higher baseline cognition (ß: 1.07, 95% CI: 0.45, 1.69), but similar rate of decline. Non-Hispanic Blacks had lower cognitive scores at baseline and throughout follow-up regardless of cancer status compared to non-Hispanic Whites and other races/ethnicities with and without cancer history. CONCLUSION: In this longitudinal retrospective study, participants with cancer history demonstrate better cognition at dementia diagnosis and no difference in cognitive decline than those without cancer history. Smoking and comorbidities attenuate this association and results indicate non-Hispanic Blacks have worse cognitive outcomes in dementia regardless of cancer history than other race/ethnicity groups. Further exploration of the role of smoking, comorbidities, and race/ethnicity on cancer and dementia-related cognitive decline is needed.

Reliability of self-report versus the capacity to consent to treatment instrument to make medical decisions in brain metastasis and other metastatic cancers.

OBJECTIVE: To evaluate the ability of persons with metastatic cancer to self-assess their medical decision-making capacity (MDC). To investigate this, we compared an objective measure of MDC with self-ratings and evaluated predictors of agreement. METHODS: Data were obtained from a cross-sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet's AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards. RESULTS: In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement. CONCLUSIONS: For less cognitively complex standards (e.g., appreciation), self-report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self-report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

Race/ethnicity, sex and insurance disparities in colorectal cancer screening among individuals with and without cardiovascular disease.

Colorectal cancer (CRC) and cardiovascular diseases (CVD) share several risk factors. We examined the relationships between CRC screening and CVD history by race/ethnicity and sex. Data from 15 states across the United States with high age-adjusted CVD rates from the 2012-2016 Behavioral Risk Factor Surveillance System were used to examine prevalence of self-reported screening for CRC among 179,276 adults ages 50-75 years with and without history of CVD. Multivariable logistic regression was used to evaluate the association between socio-demographics and CRC screening in the expansion and stable phases of the Affordable Care Act (ACA) era. Prevalence of CRC screening was high among those with history of CVD. After multivariable adjustment, Whites and Hispanics with CVD had 19% (95%[CI]: 1.13-1.26) and 50% (95%[CI]: 1.10-2.06) higher odds for CRC screening, respectively, versus those without CVD. Individuals in both sexes with CVD had higher odds for CRC screening compared those without CVD. Strikingly, the odds for CRC screening in Hispanics with history of CVD were 72% higher in the stable phase of the ACA era for the fully adjusted model. Whites and Hispanics with history of CVD are more likely to undergo CRC screening, perhaps due to greater exposure to the healthcare system due to CVD. This association was not observed in Blacks. Interventions are needed to improve CRC screening rates among Blacks, especially due to their well-documented higher risk of CVD.

Progression of Alzheimer's Disease by Self-Reported Cancer History in the Alzheimer's Disease Neuroimaging Initiative.

BACKGROUND: Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer's disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies. OBJECTIVE: To determine self-reported cancer history's effect on longitudinal AD progression in an observational study. METHODS: We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to evaluate progression to AD by self-reported all-cancer, breast, prostate, colorectal, or non-melanoma skin cancer history. Linear mixed effects models were used to examine baseline differences and rates of progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) by self-reported cancer history. Age at AD onset was examined using consensus clinical diagnoses with Cox proportional hazards regression. RESULTS: Among 1,271 participants, models revealed no significant differences in progression over time but did reveal significantly lower baseline ADAS-Cog score, indicating better cognition at a given age in those with self-reported cancer history. Cox models indicated those with self-reported cancer history had significantly later age of AD onset (HR: 0.67, 95% CI: 0.53-0.85) after adjustment for covariates. CONCLUSION: Participants with self-reported cancer history entered ADNI with better cognition and later age of AD onset, but progressed similarly to participants without such history, indicating differences in AD between those with and without self-reported cancer history emerge early in the disease course. Such differences in longitudinal progression by self-reported cancer history could affect AD trials and observational studies, given the current focus on early disease course. Further investigation is warranted with detailed longitudinal assessment of cancer and AD.

Using practice effects for targeted trials or sub-group analysis in Alzheimer's disease: How practice effects predict change over time.

OBJECTIVE: To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. METHODS: Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. RESULTS: The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. CONCLUSION: Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects.

Race, Socioeconomic Status, and Health-Care Access Disparities in Ovarian Cancer Treatment and Mortality: Systematic Review and Meta-Analysis.

BACKGROUND: Ovarian cancer remains a leading cause of death from gynecological malignancies. Race, socioeconomic status (SES), and access to health care are important predictors of quality treatment and survival. We provide a systematic review and meta-analysis on the role of these predictors on disparities in ovarian cancer treatment and mortality. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, EMBASE, and Scopus for relevant articles published between January 2000 and March 2017. We selected studies published in the United States that evaluated the role of race, SES, or health-care access on disparities in ovarian cancer treatment or survival. Pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated for each outcome using a random-effects model. RESULTS: A total of 41 studies met the inclusion criteria for systematic review. In meta-analysis, there was a 25% decrease (RR = 0.75, 95% CI = 0.66 to 0.84) in receipt of adherent ovarian cancer treatment and 18% increased risk (RR = 1.18, 95% CI = 1.11 to 1.26) of mortality for blacks compared to whites. Receipt of adherent ovarian cancer treatment was 15% lower (RR = 0.85, 95% CI = 0.77 to 0.94) in the lowest vs highest SES group and 30% lower (RR = 0.70, 95% CI = 0.58 to 0.85) among patients at lower vs higher hospital volumes. CONCLUSION: We found consistent and strong evidence for continued lack of quality ovarian cancer treatment and higher mortality among ovarian cancer patients who are black, are of low SES, and/or have poor access to care. Interventions focused on these groups targeting specific barriers to care are needed to reduce disparities in ovarian cancer treatment and mortality.

Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical Trials: A Meta-analysis.

Importance: Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. Objective: To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. Data Sources: Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. Study Selection: All studies with data on ChEI and memantine use that included assessment of specified outcome measures. Data Extraction and Synthesis: The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. Main Outcomes and Measures: Annual rate of change on the ADAS-cog. Results: Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). Conclusions and Relevance: Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.

Meta-analysis of the association between dietary inflammatory index (DII) and cancer outcomes.

Proinflammatory dietary patterns have been associated with increased cancer risk and mortality. We present a systematic review and meta-analysis of the current published literature on a dietary inflammatory index (DII) score and its association with cancer risk and mortality outcomes. Published articles from online databases (PubMed, Scopus, and Embase) examining the association between DII and any cancer risk, incidence, or mortality between 1980 and November 2016 were selected for review. Results of studies meeting inclusion criteria were summarized and meta-analyzed using STATA to generate summary measures of association across studies. Sixty-three published articles were identified from the search, and following title, abstract and full-text review, twenty-four studies met inclusion criteria. All articles calculated DII scores based on study-specific food-frequency questionnaires using methodology from the same article. Of the 24 included studies, 13 were case-control, 6 were prospective cohort, 1 was a retrospective cohort, 3 were RCTs, and 1 did not specify study design. The most common cancers examined were colorectal, breast, lung, and prostate. Individuals in the highest versus lowest DII categories had 25% increased risk of overall cancer incidence (RR: 1.25, 95% CI: 1.16-1.35), 75% higher odds of cancer (OR: 1.75, 95% CI: 1.43-2.16) and 67% increased risk of cancer mortality (RR: 1.67, 95% CI: 1.13-2.48). Upon stratification for cancer type, positive associations remained (RRbreast : RR: 1.12, 95% CI: 1.03-1.22) (RRcolorectal : 1.33, 95% CI: 1.22-1.46) (RRlung : 1.30, 95% CI: 1.13-1.50). There were consistent and significant positive associations between higher DII and cancer incidence and mortality across cancer types, study populations, and study design.