Effect of aspirin on cancer incidence and mortality in older adults

Abstract Background ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. Methods 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. Results 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). Conclusions In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group.

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Associations between Metformin and Aspirin Use on Cancer Incidence and Mortality in Older Adults

Innovation in Aging ◽

10.1093/geroni/igab046.2334 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 614-614

Author(s):

Suzanne Orchard ◽

Jonathan Broder ◽

Jessica Lockery ◽

Peter Gibbs ◽

Robyn Woods ◽

...

Keyword(s):

Older Adults ◽

Cancer Risk ◽

Cancer Incidence ◽

Community Dwelling ◽

Uncontrolled Diabetes ◽

Increased Risk ◽

Incidence And Mortality ◽

Significant Difference ◽

Risk Of Cancer ◽

Related Mortality

Abstract Diabetes increases risk of malignancies, and this association increases with age. Metformin may protect against cancer development and progression, but results are mixed and limited to younger cohorts. We examined whether metformin, in the presence or absence of aspirin, reduces incident cancer and cancer-related mortality in older adults. ASPirin in Reducing Events in the Elderly (ASPREE) was a primary prevention trial of daily aspirin vs placebo which enrolled community-dwelling adults from Australia (70+ years) and the US (65+ years for minorities) followed for a median of 4.7 years. Invasive cancer was adjudicated by an expert panel. Cox proportional-hazards models, controlling for age at randomization and known cancer risk factors, were used to analyse the relationship between baseline metformin use, randomized treatment arm, cancer incidence (first in-trial cancer) and mortality. For participants with controlled diabetes, there was a significant reduction in cancer mortality in metformin users compared to nonusers (Adjusted [Adj] HR=0.24, 95%CI=0.07, 0.80), but not for cancer incidence (Adj HR=0.61, 95%CI=0.29, 1.27). For participants with uncontrolled diabetes, there was no significant difference in cancer incidence (Adj HR=0.95, 95%CI=0.66, 1.38) or mortality (Adj HR=1.18, 95%CI=0.62, 2.26) between metformin and non-metformin users. Uncontrolled diabetes, irrespective of metformin use, increased risk of cancer incidence and mortality compared to non-diabetics. Aspirin did not modify the effect of metformin on cancer incidence or mortality. Our findings show that metformin may have protective effects against cancer-related mortality for those older persons whose diabetes is well-controlled, and underscores the importance of diabetes control to minimise cancer risk.

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The ACHIEVE Trial: Lessons Learned From Nesting a Randomized Controlled Trial Within an Observational Cohort Study

Innovation in Aging ◽

10.1093/geroni/igaa057.2950 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 811-811

Author(s):

Jennifer Deal ◽

Nicholas Reed ◽

David Couper ◽

Kathleen Hayden ◽

Thomas Mosley ◽

...

Keyword(s):

Older Adults ◽

Randomized Controlled Trial ◽

Observational Study ◽

Cognitive Decline ◽

Controlled Trial ◽

Lessons Learned ◽

Community Dwelling ◽

Randomized Controlled ◽

Study Staff ◽

Increased Risk

Abstract Hearing impairment in older adults is linked to accelerated cognitive decline and a 94% increased risk of incident dementia in population-based observational studies. Whether hearing treatment can delay cognitive decline is unknown but could have substantial clinical and public health impact. The NIH-funded ACHIEVE randomized controlled trial of 977 older adults aged 70-84 years with untreated mild-to-moderate hearing loss, is testing the efficacy of hearing treatment versus health education on cognitive decline over 3 years in community-dwelling older adults (Clinicaltrials.gov Identifier: NCT03243422.) This presentation will describe lessons learned from ACHIEVE’s unique study design. ACHIEVE is nested within a large, well-characterized multicenter observational study, the Atherosclerosis Risk in Communities Study. Such nesting within an observational study maximizes both operational and scientific efficiency. With trial results expected in 2022, this presentation will focus on the benefits gained in design and recruitment/retention, including dedicated study staff, well-established protocols, and established study staff-participant relationships. Part of a symposium sponsored by Sensory Health Interest Group.

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Dancing Against falls iN Community-dwElling older adults (DANCE): a study protocol of a stratified, block-randomised trial

Injury Prevention ◽

10.1136/injuryprev-2021-044224 ◽

2021 ◽

pp. injuryprev-2021-044224

Author(s):

Mikkel Jacobi Thomsen ◽

Matthew Liston ◽

Merete Grothe Christensen ◽

Peter Vestergaard ◽

Rogerio Pessoto Hirata

Keyword(s):

Older Adults ◽

Randomised Trial ◽

Community Dwelling ◽

Control Group ◽

Mineral Density ◽

Risk Of Death ◽

Dance Training ◽

Increased Risk ◽

Risk Factors For Falls ◽

Community Dwelling Older Adults

BackgroundUnintentional falls among older adults are of primary importance due to their impact on quality of life. Falling accounts for 95% of hip fractures, leading to an approximately six times increased risk of death within the first 3 months. Furthermore, physical and cognitive parameters are risk factors for falls. The purpose of this study is to examine the effect of a 6-month salsa dance training intervention, compared with regular fitness circuit training and a control group.MethodsThis study will include 180 older adults: 90 healthy patients and 90 patients with osteoporosis. Participants will be allocated randomly in either of the groups, stratified according to age. Training groups will receive 2 weekly 1-hour training sessions, continuously through 6 months. Participants will be tested at baseline and 6 and 18 months post baseline. Primary outcome will be number of falls and secondary outcomes include bone mineral density, body composition, pain evaluation, weekly physical activity, single-task and dual-task gait patterns, balance, Fullerton Functional Fitness Test and assessment of the mini-BESTest.DiscussionThis study will investigate the effects of a specially designed dance training programme (Dancing Against falls iN Community-dwElling older adults (DANCE)) to reduce the risk of falling among older adults. The study will investigate the effect against an active and passive comparator, resulting in the possibility to state, if DANCE training should be an alternative to traditional training.Trial registration numberNCT03683849.

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Comparing the Effects of Single-Task versus Dual-Task Balance Training on Gait Smoothness and Functional Balance in Community-Dwelling Older Adults: A Randomized Controlled Trial

Journal of Aging and Physical Activity ◽

10.1123/japa.2020-0523 ◽

2021 ◽

pp. 1-8

Author(s):

Samira Javadpour ◽

Ehsan Sinaei ◽

Reza Salehi ◽

Shahla Zahednejad ◽

Alireza Motealleh

Keyword(s):

Older Adults ◽

Dual Task ◽

Controlled Trial ◽

Balance Training ◽

Community Dwelling ◽

Control Group ◽

Timed Up And Go ◽

Training Groups ◽

Significant Difference ◽

Community Dwelling Older Adults

To compare the effects of single- versus dual-task balance training on the gait smoothness and balance of community-dwelling older adults, 69 volunteers were randomized to single-, dual-task training, and control (no intervention) groups. Exercises were received in 18 sessions through 6 weeks. The gait smoothness was measured by the harmonic ratio of trunk accelerations using a triaxial accelerometer. Balance performance was assessed through the Fullerton Advanced Balance scale, Timed Up and Go test, Activities-specific Balance Confidence, and gait speed. After the trial, all variables improved significantly in the training groups. Moreover, differences in the mean change of all variables, except the Timed Up and Go test, were statistically significant between the interventional groups and the control group, but no significant difference was reported between the two training groups. This study suggests that balance training can improve gait smoothness as well as balance status in healthy older adults.

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Effect of comorbidity on the risk of death associated with antipsychotic use among community-dwelling older adults

International Psychogeriatrics ◽

10.1017/s1041610212000117 ◽

2012 ◽

Vol 24 (7) ◽

pp. 1058-1064 ◽

Cited By ~ 7

Author(s):

Natasa Gisev ◽

Sirpa Hartikainen ◽

Timothy F. Chen ◽

Mikko Korhonen ◽

J. Simon Bell

Keyword(s):

Older Adults ◽

Respiratory Disease ◽

Population Based ◽

Community Dwelling ◽

Risk Of Death ◽

Hazard Ratios ◽

Increased Risk ◽

Cox Proportional Hazard Models ◽

Antidepressant Use ◽

Community Dwelling Older Adults

ABSTRACTBackground: Antipsychotics are associated with adverse events and mortality among older adults with dementia. The objective of this study was to evaluate the risk of death associated with antipsychotic use among community-dwelling older adults with a range of comorbidities.Methods: This was a population-based cohort study of all 2,224 residents of Leppävirta, Finland, aged ≥65 years on 1 January 2000. Records of all reimbursed drug purchases were extracted from the Finnish National Prescription Register and diagnostic data were obtained from the Special Reimbursement Register. All-cause mortality was evaluated over a nine-year follow-up period. Time-dependent Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality of antipsychotic use compared to non-use.Results: In total, 332 residents used antipsychotics between 2000 and 2008. The unadjusted HR for risk of death associated with antipsychotic use was 2.71 (95% CI = 2.3–3.2). After adjusting for baseline age, sex, antidepressant use, and diagnostic confounders, the HR was 2.07 (95% CI = 1.73–2.47). The adjusted HR was the highest among antipsychotic users with baseline respiratory disease (HR = 2.21, 95% CI = 1.30–3.76).Conclusions: The increased risk of death associated with antipsychotic use was similar across diagnostic categories, the highest being among those with baseline respiratory disease. However, the results should be interpreted with caution, as the overall sample size of antipsychotic users was small. As in other observational studies, residual confounding may account for the higher mortality observed among antipsychotic users. Further research is needed to confirm these findings.

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Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy

Life ◽

10.3390/life11101032 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1032

Author(s):

Oleksandr Oliynyk ◽

Wojciech Barg ◽

Anna Slifirczyk ◽

Yanina Oliynyk ◽

Serhij Dubrov ◽

...

Keyword(s):

Unfractionated Heparin ◽

Controlled Trial ◽

Logistic Regression Models ◽

Risk Of Death ◽

Increased Risk ◽

Significant Difference ◽

Coronavirus Infection ◽

Randomised Controlled ◽

Therapeutic Doses ◽

Different Doses

Background: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). Methods: A randomised, controlled trial enrolled 126 patients hospitalised in the intensive care unit with severe COVID-19 complicated by CAC. The effects of LMWH at preventive and therapeutic doses and UFH at therapeutic doses on mortality and intubation rates were compared. Results: The number of intubations and deaths showed no significant difference depending on the anticoagulant therapy used. However, multivariate logistic regression models revealed an increased risk of intubation (p = 0.026, odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.15–9.59), and an increased risk of death (p = 0.046, OR = 3.01, 95% CI 1.02–8.90), for patients treated with LMWH at a prophylactic dose but not at a therapeutic dose as compared to patients treated with UFH when controlling for other risk factors. Conclusions: The use of unfractionated heparin in the treatment of COVID-19-associated coagulopathy seems to be more effective at reducing the risk of intubation and death than enoxaparin at prophylactic doses.

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Tobacco still haunting Kentuckians: Adolescent and young adult (AYA) cancer trend from the Kentucky SEER database.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13626 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13626-e13626

Author(s):

Aasems Jacob ◽

Saurabh Parasramka ◽

Zhonglin Hao ◽

Eric B. Durbin

Keyword(s):

Cancer Incidence ◽

Cox Regression ◽

The State ◽

Adolescent And Young Adult ◽

Second Hand Smoke ◽

Cancer Center ◽

Seer Database ◽

Risk Of Death ◽

Incidence And Mortality ◽

Significant Difference

e13626 Background: Kentucky has the highest incidence and mortality for AYA cancers in the US. When the incidence of AYA cancers increased 4% between 2012-16 nationally, it was 12.3% in the state of Kentucky. Understanding the burden and factors associated with it may help develop effective risk reduction strategies. Methods: SEER database was used for analyzing population estimates (2012-2016) while records from the NCI-designated cancer center in the state was used to assess current trends and clinicopathologic features. Pearson test was used to estimate correlation and Kaplan-Meier and Cox regression models were used to compare survival outcomes. Results: A total of 5825 AYA patients were identified in the state’s SEER database between 2012-16. A majority (62.4%) were female, from non-Appalachian region (71%) and rural counties (64%). Thyroid, breast, melanoma, cervical and CNS malignancies were the most common. While sarcoma, leukemia and gastric cancer decreased in incidence, breast, melanoma, cervical and colorectal cancer have increased from 2012-2016, similar to a general trend nation-wide. County-wise estimation of cancer incidence showed a significant correlation with prevalence of smoking (Pearson r = 0.34, p < 0.001) independent of educational, employment or economic status. A total of 1129 AYA cancer patients treated between 2016-19 at the Markey Cancer Center were analyzed. Baseline characteristics were similar to statewide trend. About 10% of the cancers were metastatic at diagnosis and 14% died from the disease. Nearly half (44%) of the patients were smokers. Smoking was independently associated with higher risk of death (HR 0.46 95%CI 0.33, 0.64, p < 0.0001) and early cancer recurrence (HR 0.56, 95%CI 0.3, 0.9, p = 0.026). Metastatic disease at diagnosis was also more common among smokers compared to non-smokers. (58% vs 41%, p = 0.002). There was no significant difference in OS or risk of recurrence between rural/urban or Appalachian/Non-Appalachian counties. Conclusions: The high prevalence of smoking (24.3%), especially among youth (14.3%) could be the root of the higher incidence of AYA cancers in the state of KY although multiple socio-economic and geographic factors might be influencing. Second-hand smoke exposure at home is also the highest in the country at 32% with rates as high as 80% in some counties. Awareness about these disturbing statistics is required to set in motion more community and legislative interventions to reduce cancer incidence among the youth.

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Effects of Physical and Cognitive Training on Falls and Concern about Falling in Older Adults: Results from a Randomized Controlled Trial

The Journals of Gerontology Series A ◽

10.1093/gerona/glab375 ◽

2021 ◽

Author(s):

Katri M Turunen ◽

Anna Tirkkonen ◽

Tiina Savikangas ◽

Tuomo Hänninen ◽

Markku Alen ◽

...

Keyword(s):

Physical Activity ◽

Older Adults ◽

Randomized Controlled Trial ◽

Cognitive Training ◽

Physical Training ◽

Controlled Trial ◽

Community Dwelling ◽

Randomized Controlled ◽

Significant Difference

Abstract Background The aim of this study is to investigate whether combined cognitive and physical training provides additional benefits to fall prevention when compared with physical training alone in older adults. Methods This is a prespecified secondary analysis of a single-blind, randomized controlled trial involving community-dwelling men and women aged 70 to 85 years who did not meet the physical activity guidelines. The participants were randomized into combined physical and cognitive training (PTCT, n=155) and physical training (PT, n=159) groups. PT included supervised and home-based physical exercises following the physical activity recommendations. PTCT included PT and computer-based cognitive training. The outcome was the rate of falls over the 12-month intervention (PTCT, n=151 and PT, n=155) and 12-month postintervention follow-up (PTCT, n=143 and PT, n=148). Falls were ascertained from monthly diaries. Exploratory outcomes included the rate of injurious falls, faller/recurrent faller/fall-related fracture status, and concern about falling. Results Estimated incidence rates of falls per person-year were 0.8 (95% CI 0.7–1.1) in the PTCT and 1.1 (95% CI 0.9–1.3) in the PT during the intervention and 0.8 (95% CI 0.7–1.0) versus 1.0 (95% CI 0.8–1.1), respectively, during the postintervention follow-up. There was no significant difference in the rate of falls during the intervention (incidence rate ratio [IRR] 0.78; 95% CI 0.56–1.10, p=0.152) or in the follow-up (IRR=0.83; 95% CI 0.59–1.15, p=0.263). No significant between-group differences were observed in any exploratory outcomes. Conclusion A yearlong PTCT intervention did not result in a significantly lower rate of falls or concern about falling than PT alone in older community-dwelling adults.

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Incident mobility disability, parkinsonism, and mortality in community-dwelling older adults

PLoS ONE ◽

10.1371/journal.pone.0246206 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246206

Author(s):

Shahram Oveisgharan ◽

Lei Yu ◽

David A. Bennett ◽

Aron S. Buchman

Keyword(s):

Older Adults ◽

Rating Scale ◽

Cox Model ◽

Motor Impairment ◽

Community Dwelling ◽

Mobility Disability ◽

Risk Of Death ◽

Increased Risk ◽

Disease Rating ◽

Community Dwelling Older Adults

Background Mobility disability and parkinsonism are associated with decreased survival in older adults. This study examined the transition from no motor impairment to mobility disability and parkinsonism and their associations with death. Methods 867 community-dwelling older adults without mobility disability or parkinsonism at baseline were examined annually. Mobility disability was based on annual measured gait speed. Parkinsonism was based on the annual assessment of 26 items from the motor portion of the Unified Parkinson’s Disease Rating Scale. A multistate Cox model simultaneously examined the incidences of mobility disability and parkinsonism and their associations with death. Results Average age at baseline was 75 years old and 318 (37%) died during 10 years of follow-up. Mobility disability was almost 2-fold more common than parkinsonism. Some participants developed mobility disability alone (42%), or parkinsonism alone (5%), while many developed both (41%). Individuals with mobility disability or parkinsonism alone had an increased risk of death, but their risk was less than the risk in individuals with both impairments. The risk of death did not depend on the order in which impairments occurred. Conclusion The varied patterns of transitions from no motor impairment to motor impairment highlights the heterogeneity of late-life motor impairment and its contribution to survival. Further studies are needed to elucidate the underlying biology of these different transitions and how they might impact survival.

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The (cost-)effectiveness of an implemented fall prevention intervention on falls and fall-related injuries among community-dwelling older adults with an increased risk of falls: protocol for the in balance randomized controlled trial

BMC Geriatrics ◽

10.1186/s12877-021-02334-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maaike van Gameren ◽

Daniël Bossen ◽

Judith E. Bosmans ◽

Bart Visser ◽

Sanne W. T. Frazer ◽

...

Keyword(s):

Older Adults ◽

Cost Effectiveness ◽

Fall Prevention ◽

Controlled Trial ◽

Cost Effective ◽

Community Dwelling ◽

Prevention Intervention ◽

Increased Risk ◽

Risk Of Falls ◽

Fall Prevention Intervention

Abstract Background Falls and fall-related injuries among older adults are a serious threat to the quality of life and result in high healthcare and societal costs. Despite evidence that falls can be prevented by fall prevention programmes, practical barriers may challenge the implementation of these programmes. In this study, we will investigate the effectiveness and cost-effectiveness of In Balance, a fourteen-week, low-cost group fall prevention intervention, that is widely implemented in community-dwelling older adults with an increased fall risk in the Netherlands. Moreover, we will be the first to include cost-effectiveness for this intervention. Based on previous evidence of the In Balance intervention in pre-frail older adults, we expect this intervention to be (cost-)effective after implementation-related adjustments on the target population and duration of the intervention. Methods This study is a single-blinded, multicenter randomized controlled trial. The target sample will consist of 256 community-dwelling non-frail and pre-frail adults of 65 years or older with an increased risk of falls. The intervention group receives the In Balance intervention as it is currently widely implemented in Dutch healthcare, which includes an educational component and physical exercises. The physical exercises are based on Tai Chi principles and focus on balance and strength. The control group receives general written physical activity recommendations. Primary outcomes are the number of falls and fall-related injuries over 12 months follow-up. Secondary outcomes consist of physical performance measures, physical activity, confidence, health status, quality of life, process evaluation and societal costs. Mixed model analyses will be conducted for both primary and secondary outcomes and will be stratified for non-frail and pre-frail adults. Discussion This trial will provide insight into the clinical and societal impact of an implemented Dutch fall prevention intervention and will have major benefits for older adults, society and health insurance companies. In addition, results of this study will inform healthcare professionals and policy makers about timely and (cost-)effective prevention of falls in older adults. Trial registration Netherlands Trial Register: NL9248 (registered February 13, 2021).

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