Interactions between caregiving and sex and the antibody response to COVID-19 vaccination.

OBJECTIVE: Antibody response to vaccination is a powerful paradigm for studying the effects of chronic stress on immune function. In the present study, we used this paradigm to examine the interaction between caregiving (as a type of chronic stress) and sex on the antibody response to a single dose of a COVID-19 vaccination; recent research has called for examination of sex differences on health outcomes among family caregivers. A three-way interaction between caregiving, sex and psychological distress was also examined. METHODS: COVID-19 antibody data was extracted from 165 caregivers (98 females) and 386 non-caregivers (244 females) from the UK's Understanding Society COVID-19 study. Relevant socio-demographics, health and lifestyle, and distress variables were gathered as potential covariates. RESULTS: In a 2 x 2 ANOVA we found the interaction between caregiving and sex was significant; male caregivers had a lower antibody response to the vaccine compared to female caregivers F (1,547), =24.82, p < .001, η2 = .043. Following adjustment, male caregivers had the lowest antibody response relative to all other groups. The three-way interaction model, controlling for covariates was also significant, R2 = .013, p = .049; the conditional effects for the three-way interaction revealed that male caregivers, compared to the other groups had a lower antibody response at both low and medium levels of psychological distress. CONCLUSION: This study found evidence of a three-way interaction between caregiving, sex and distress on antibody response. Male caregivers had poorer antibody response to a single shot of the COVID-19 vaccination than female caregivers and male and female non-caregivers and this was evident at low and medium levels of distress. Our findings will be discussed in relation to the caregiver-and sex interactions during the pandemic.

A Mixed Methods Feasibility Study of Machine-Based Resistance Training With Prefrail Older Adults in Residential Care: The Keeping Active in Residential Elderly Trial II.

Physical activity is an effective, proactive intervention to reduce or reverse frailty and functional decline. However, uncertainty exists about the feasibility and impact of resistance training on multidimensional health in prefrail older adults in residential care. This mixed methods feasibility study assessed practicability with limited efficacy testing on health and functional outcomes. Eleven prefrail older adults participated in a 6-week progressive resistance training protocol three times per week. The intervention and measures were found to be appropriate and acceptable by those who completed the trial, with participants self-reporting improved well-being, mood, and function. Analysis identified several barriers to recruitment, including prior commitments, seasonal impact, and session timing, and offered potential solutions with further recommendations for program refinement prior to a definitive randomized controlled trial. These findings add to our understanding of prefrail older adults' preferences regarding participation in physical activity research and the perceived benefits of resistance training. This trial was registered with ClinicalTrials.gov: NCT03141879.

Beyond the Beta Rebound: Post-Task Responses in Oscillatory Activity follow Cessation of Working Memory Processes.

Post-task responses (PTRs) are transitionary responses occurring for several seconds between the end of a stimulus/task and a period of rest. The most well-studied of these are beta band (13 - 30 Hz) PTRs in motor networks following movement, often called post-movement beta rebounds, which have been shown to differ in patients with schizophrenia and autism. Previous studies have proposed that beta PTRs reflect inhibition of task-positive networks to enable a return to resting brain activity, scaling with cognitive demand and reflecting cortical self-regulation. It is unknown whether PTRs are a phenomenon of the motor system, or whether they are a more general self-modulatory property of cortex that occur following cessation of higher cognitive processes as well as movement. To test this, we recorded magnetoencephalography (MEG) responses in 20 healthy participants to a working-memory task, known to recruit cortical networks associated with higher cognition. Our results revealed PTRs in the theta, alpha and beta bands across many regions of the brain, including the dorsal attention network (DAN) and lateral visual regions. These PTRs increased significantly (p < 0.05) in magnitude with working-memory load, an effect which is independent of oscillatory modulations occurring over the task period as well as those following individual stimuli. Furthermore, we showed that PTRs are functionally related to reaction times in left lateral visual (p < 0.05) and left parietal (p < 0.1) regions, while the oscillatory responses measured during the task period are not. Importantly, motor PTRs following button presses did not modulate with task condition, suggesting that PTRs in different networks are driven by different aspects of cognition. Our findings show that PTRs are not limited to motor networks but are widespread in regions which are recruited during the task. We provide evidence that PTRs have unique properties, scaling with cognitive load and correlating significantly with behaviour. Based on the evidence, we suggest that PTRs inhibit task-positive network activity to enable a transition to rest, however, further investigation is required to uncover their role in neuroscience and pathology.

Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World.

The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.

The reliability and suitability of strength assessments in frail and pre-frail older adults: recommendations for strength testing in older populations.

BACKGROUND: Lifelong strength is fundamental to physical function, health, and quality of life. Reliable appropriate strength assessment measures for older adults play an important role in effective evaluation of baseline ability and exercise prescription to counter disease and disuse. This study aimed to investigate the within-session reliability of maximal isometric knee extension and flexion, hip abduction and adduction, and handgrip strength measures in frail and pre-frail older adults. METHOD: The study was conducted at a residential care home in Birmingham, UK. All care home residents aged ≥ 65 years; pre-frail or frail according to the Fried Frailty phenotype criteria; able to speak and read English; not currently involved in any other clinical trial; without severe sensory impairments; and with a predicted life expectancy greater than the trial length were eligible. Maximal isometric lower limb testing was performed using specialised resistance training equipment and a portable measurement device, and grip strength was assessed using a portable dynamometer. All eligible participants attended a single testing session and performed three trials per measure. Peak force measures were obtained for analysis. Within-session reliability for each measure was calculated from repeated-measures analysis of variance, intraclass correlation coefficients (ICC), and coefficients of variation (CV) with 95% confidence intervals. RESULTS: Eleven frail and eleven pre-frail older adults participated in the study. Within-session absolute and relative measures were found to be reliable with the highest overall repeatability indicated between trial 2 and trial 3 for knee extension, hip abduction, and handgrip (CV ≤ 4.65%, ICC ≥ 0.96) with variation evident across all measures, except knee extension, from trial 1 to 2. CONCLUSIONS: Overall, maximal isometric strength in frail and pre-frail older adults with no previous testing experience can be measured with good to high reliability within their first testing session. An initial two familiarisation trials followed by two measurement trials is recommended to achieve the highest level of overall repeatability. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov: NCT03141879 on 05/05/2017.

Physical Activity Influences Cortisol and Dehydroepiandrosterone (Sulfate) Levels in Older Adults: A Systematic Review and Meta-Analysis.

Age-related changes affect the ratio between two steroid hormones of the hypothalamic-pituitary-adrenal axis, cortisol and dehydroepiandrosterone (sulfate) (DHEA[S]). Physical activity (PA) may buffer the effects of chronic stress and counteract the aging decline of DHEA(S). Therefore, a systematic review was conducted to understand how PA influences physiological markers of cortisol and/or DHEA(S) and whether there is a difference in observational associations or experimental effects in older adults aged 65 years and older. A narrative synthesis was performed on nine observational studies, and meta-analyses were performed on 22 randomized controlled trials. There was low- to moderate-quality evidence that regular PA beneficially reduces cortisol and increases DHEA(S) levels. Subgroup analyses showed no clinically important differences between men and women, different exercise modalities, or health states. The findings cautiously suggest that regular PA of older adults' own choice that they find enjoyable could be recommended to improve cortisol and/or DHEA(S) levels.

Dimensions of Physical Activity Are Important in Managing Anxiety in Older Adults: A Systematic Review and Meta-Analysis.

Physical activity (PA) is a known approach for managing anxiety symptoms in older adults. This systematic review and meta-analysis address the benefits of PA and its dimensions (frequency, session time, type, and intervention period) on anxiety symptoms in older adults aged 65 years and above. Searches covered eight databases reporting eight randomized controlled trials (RCTs) and five non-RCTs. Meta-analysis of RCTs (standardized mean difference = -0.41; 95% confidence interval [-0.58, -0.24]; p < .00001) and Fisher's method of combining p values for non-RCTs supported the effectiveness of PA for managing anxiety symptoms in older adults. Subgroup analysis revealed significant effects for all PA types, session times, frequency, and intervention periods compared with control groups, albeit with different magnitudes of effect. In conclusion, although some dimensions of PA contribute to its effectiveness for anxiety, PA intensity and mode required to maximize PA effects remain unclear.

Social cohesion and loneliness are associated with the antibody response to COVID-19 vaccination.

BACKGROUND: Recent research has suggested that psychosocial factors influence the antibody response to vaccine, including SARS-CoV-2 (COVID-19) vaccines. Here we investigated whether social cohesion and loneliness were predictive of antibody response to a single dose of a COVID-19 vaccine. We also tested if the association between social cohesion and antibody response was mediated by feelings of loneliness. METHODS: Participants (N = 676) COVID-19 antibody data were extracted from March 2021 wave of the Understanding Society COVID-19 study from the UK. Relevant socio-demographics, health and lifestyle, loneliness, social cohesion indices were also used in a series of hierarchical linear regression to test our main hypotheses. RESULTS: After controlling for covariates (e.g., age and chronic health conditions), lower social cohesion was associated with a lower antibody response. Further, the association between social cohesion and poorer antibody responses was mediated by loneliness; those reporting lower social cohesion also reported higher loneliness, which in turn was associated with lower antibody response. CONCLUSION: This study confirms that feelings of 'being in it together' relate to the strength of the antibody response to COVID-19 vaccination, emphasising the importance of the social cohesion agenda during the pandemic.

A Randomized Controlled Feasibility Trial Evaluating a Resistance Training Intervention With Frail Older Adults in Residential Care: The Keeping Active in Residential Elderly Trial.

Frailty is associated with negative health outcomes, disability, and mortality. Physical activity is an effective intervention to improve functional health status. However, the effect of resistance training on multidimensional health in frail older adults remains unclear. This randomized controlled trial was conducted in a U.K. residential care home to assess feasibility with limited efficacy testing on health and functional outcomes and to inform a future definitive randomized controlled trial. Eleven frail older adults (>65 years) completed a 6-week machine-based resistance training protocol three times a week. Uptake and retention were greater than 80%. The measures and intervention were found to be acceptable and practicable. The analyses indicated large improvements in functional capacity, frailty, and strength in the intervention group compared with the controls. These findings support the feasibility of a definitive randomized controlled trial and reinforce the value of resistance training in this population. This trial was registered with ClinicalTrials.gov: NCT03141879.

Cardiovascular Stress Reactivity and Health: Recent Questions and Future Directions.

OBJECTIVE: High cardiovascular reactions to psychological stress are associated with the development of hypertension, systemic atherosclerosis, and cardiovascular disease. However, it has become apparent that low biological stress reactivity also may have serious consequences for health, although less is known about the mechanisms of this. The objectives of this narrative review and opinion article are to summarize and consider where we are now in terms of the usefulness of the reactivity hypothesis and reactivity research, given that both ends of the reactivity spectrum seem to be associated with poor health, and to address some of the key criticisms and future challenges for the research area. METHODS: This review is authored by the members of a panel discussion held at the American Psychosomatic Society meeting in 2019, which included questions such as the following: How do we measure high and low reactivity? Can high reactivity ever indicate better health? Does low or blunted reactivity simply reflect less effort on task challenges? Where does low reactivity originate from, and what is a low reactor? RESULTS: Cardiovascular (and cortisol) stress reactivity are used as a model to demonstrate an increased understanding of the different individual pathways from stress responses to health/disease and show the challenges of how to understand and best use the reconstruction of the long-standing reactivity hypothesis given recent data. CONCLUSIONS: This discussion elucidates the gaps in knowledge and key research issues that still remain to be addressed in this field, and that systematic reviews and meta-analyses continue to be required.

Daily stair climbing is associated with decreased risk for the metabolic syndrome.

BACKGROUND: Stair climbing can be a vigorous lifestyle physical activity, and is associated with healthier lipoprotein profiles, lower body weight and blood pressure, as well as higher aerobic fitness. The present analysis of data from a cohort of late middle-aged men and women examined the association between daily stair climbing and the metabolic syndrome. METHODS: Data from 782 (423 women) participants (mean (SD) age 58.3 (0.95) years in the Dutch Famine Birth Cohort Study (2002-2004) were used to examine the cross-sectional association between self-reported daily stair climbing and the metabolic syndrome. Stair climbing was assessed by the question 'Do you climb stairs daily?' and the metabolic syndrome was defined using the established five components relating to lipid fractions, blood glucose levels, blood pressure and abdominal obesity. RESULTS: Not climbing stairs daily was associated with an increased incidence of the metabolic syndrome (OR = 1.90, 95% CI = 1.23, 2.92, p = 0.004) and a greater number of its components (F1,780 = 8.48, p = 0.004): these associations were still evident after adjusting for a variety of potential confounders. CONCLUSIONS: The most likely explanation for the current findings is that daily stair climbing may be protective against the metabolic syndrome. This result reinforces public health recommendations for increased stair climbing with evidence from physiological outcomes.

The CO2 stimulus duration and steady-state time point used for data extraction alters the cerebrovascular reactivity outcome measure.

NEW FINDINGS: What is the central question of this study? Cerebrovascular reactivity (CVR) is a common functional test to assess brain health, and impaired CVR has been associated with all-cause cardiovascular mortality: does the duration of the CO2 stimulus and the time point used for data extraction alter the CVR outcome measure? What is the main finding and its importance? This study demonstrated CVR measures calculated from 1 and 2 min CO2 stimulus durations were significantly higher than CVR calculated from a 4 min CO2 stimulus. CVRs calculated from the first 2 min of the CO2 stimulus were significantly higher than CVR values calculated from the final minute if the duration was ≥4 min. This study highlights the need for consistent methodological approaches. ABSTRACT: Cerebrovascular reactivity to carbon dioxide (CVR) is a common functional test to assess brain vascular health, though conflicting age and fitness effects have been reported. Studies have used different CO2 stimulus durations to induce CVR and extracted data from different time points for analysis. Therefore, this study examined whether these differences alter CVR and explain conflicting findings. Eighteen healthy volunteers (24 ± 5 years) inhaled CO2 for four stimulus durations (1, 2, 4 and 5 min) of 5% CO2 (in air) via the open-circuit Douglas bag method, in a randomized order. CVR data were derived from transcranial Doppler (TCD) measures of middle cerebral artery blood velocity (MCAv), with concurrent ventilatory sensitivity to the CO2 stimulus ( V̇E,CO2 ). Repeated measures ANOVAs compared CVR and V̇E,CO2 measures between stimulus durations and steady-state time points. An effect of stimulus duration was observed (P = 0.002, η² = 0.140), with 1 min (P = 0.010) and 2 min (P < 0.001) differing from 4 min, and 2 min differing from 5 min (P = 0.019) durations. V̇E,CO2 sensitivity increased ∼3-fold from 1 min to 4 and 5 min durations (P < 0.001, η² = 0.485). CVRs calculated from different steady-state time points within each stimulus duration were different (P < 0.001, η² = 0.454), specifically for 4 min (P = 0.001) and 5 min (P < 0.001), but not 2 min stimulus durations (P = 0.273). These findings demonstrate that methodological differences alter the CVR measure.

Malnutrition is associated with dynamic physical performance.

BACKGROUND: Malnutrition and poor physical performance are both conditions that increase in prevalence with age; however, their interrelation in a clinically relevant population has not been thoroughly studied. AIMS: This study aimed to determine the strength of the association between malnutrition and measures of both static and dynamic physical performance in a cohort of geriatric outpatients. METHODS: This cross-sectional study included 286 older adults (mean age 81.8, SD 7.2 years, and 40.6% male) who were referred to geriatric outpatient mobility clinics. The presence of malnutrition was determined using the Short Nutritional Assessment Questionnaire (SNAQ, cut-off ≥ 2 points). Measures of dynamic physical performance included timed up and go (TUG), 4-m walk test, and chair stand test (CST). Static performance encompassed balance tests and hand grip strength (HGS). Physical performance was standardized into sex-specific Z-scores. The association between malnutrition and each individual measure of physical performance was assessed using linear regression analysis. RESULTS: 19.9% of the cohort was identified as malnourished. Malnutrition was most strongly associated with CST and gait speed; less strong but significant associations were found between malnutrition and TUG. There was no significant association between malnutrition and HGS or balance. DISCUSSION: Physical performance was associated with malnutrition, specifically, dynamic rather than static measures. This may reflect muscle power being more impacted by nutritional status than muscle strength; however, this needs to be further addressed. CONCLUSIONS: Malnutrition is associated with dynamic physical performance in geriatric outpatients, which should inform diagnosis and treatment/prevention strategies.

A novel behavioural INTErvention to REduce Sitting Time in older adults undergoing orthopaedic surgery (INTEREST): results of a randomised-controlled feasibility study.

BACKGROUND: Osteoarthritis is a prevalent condition in older adults that causes many patients to require a hip or knee replacement. Reducing patients' sedentariness prior to surgery may improve physical function and post-operative outcomes. METHODS: We conducted a pragmatic randomised-controlled feasibility study with 2:1 allocation into intervention or usual care groups. The intervention, based on Self-Determination Theory, involved techniques to reduce sedentary behaviour, including motivational interviewing, setting of behavioural goals, and more. The primary outcome was feasibility, assessed using mixed methods. We included exploratory measures to inform a future definitive trial, such as ActivPal3 accelerometry to measure movement, the Short Physical Performance Battery (SPPB), Basic Psychological Needs, and cardiometabolic biomarkers. Assessments were at baseline, 1-week pre-surgery, and 6-week post-surgery. RESULTS: We recruited 35 participants aged ≥ 60 years approximately 8 weeks before hip or knee arthroplasty. Participant uptake rate was 14.2%, and retention rate 85.7%. Participants were very satisfied with the study which was found to be feasible with some modifications. Exploratory within-group comparisons found that the intervention has potential to improve SPPB by 0.71 points from baseline to pre-surgery, a clinically significant increase, and reduce sedentary time by up to 66 min d-1. CONCLUSION: In this older surgical population, it is feasible to use behavioural techniques to displace sedentary time to activity and to conduct a trial spanning the period of surgical intervention. This may improve physical function and surgical outcomes. The INTEREST intervention is now ready for evaluation in a full-scale randomised-controlled trial. REGISTRATION: This trial was registered on Clinicaltrials.gov on 13/11/2018. ID: NCT03740412.

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research.

The Associations of Muscle Strength, Muscle Mass, and Adiposity With Clinical Outcomes and Quality of Life in Prevalent Kidney Transplant Recipients.

OBJECTIVE: Sarcopenia, defined as loss of both muscle strength and mass, is associated with inferior clinical outcomes and quality of life (QoL) in chronic kidney disease, but its effects are unknown in kidney transplantation. Obesity confers increased mortality risk and compromises QoL in kidney transplant recipients (KTRs), but the impacts of sarcopenic obesity remain unexplored. This study aimed to evaluate the associations of muscle strength and mass, sarcopenia, and sarcopenic obesity with clinical outcomes and QoL in KTRs. METHODS: This prospective longitudinal study enrolled 128 KTRs ≥1-year posttransplantation. Low muscle strength (by handgrip strength) and mass (by bioimpedance analysis), and a combination of both (sarcopenia) were defined as < reference cutoffs for corresponding indices. Sarcopenic obesity was defined as sarcopenia combined with fulfillment of ≥2 out of 3 criteria from (1) body mass index ≥30 kg/m2, (2) bioimpedance analysis-derived fat mass > reference cutoffs, and (3) waist circumference > World Health Organization cutoffs. Prospective follow-up data on mortality and hospitalization were collected. QoL was evaluated using Medical Outcomes Study Short Form-36 questionnaire. RESULTS: Median follow-up duration was 64 (60-72) months. Low muscle strength was independently associated with the composite endpoint of mortality and hospitalization (hazard ratio = 2.45; P = .006), and QoL (physical-related: ß = -12.2; P = .04; mental-related: ß = -9.9; P = .04). Low muscle mass (ß = -8.8; P = .04) and sarcopenia (ß = -14.7; P = .03) were associated with physical-related QoL only. No independent associations were found between muscle mass, sarcopenia, and sarcopenic obesity with the composite outcome of mortality and hospitalization. CONCLUSION: Low muscle strength is common among KTRs, conferring poor prognosis in the medium term. Future research on strength training may prove valuable in improving kidney transplantation outcomes.

Undiagnosed Obstructive Sleep Apnea and Physical Activity in Older Manual Workers.

Cardiovascular disease is a negative health outcome of obstructive sleep apnea (OSA). Risk factors associated with OSA development include low physical activity (PA), high body mass index (BMI), and increasing age (>50 years), and weight loss is usually recommended as treatment. This cross-sectional study examined the association between PA, BMI, and OSA severity in manual workers. Fifty-five participants (23 females and 32 males; mean age 55.2 years), were examined for OSA and completed a PA and anthropometric assessment. On average, OSA severity was mild, PA levels were moderate, and 32% of the sample was classified as obese. PA was negatively associated with OSA severity, but BMI strongly independently predicted OSA severity, with no evidence of mediation. As both PA and BMI were significantly associated with OSA in older manual workers, increasing PA should also be a focus of treatment for OSA.

Anxiety, history of childhood adversity, and experiencing chronic pain in adulthood: A systematic literature review and meta-analysis.

BACKGROUND: When considering factors that may impact chronic pain experiences in adulthood, adverse childhood experiences (ACEs) and anxiety should be considered. The literature on the associations between these 3 variables remains unclear. OBJECTIVE: To summarize the existing literature on the relationship between ACEs and anxiety on chronic pain experience in adults, and examine the association between ACEs and anxiety. METHODS: A systematic literature review (SLR) and meta-analysis was used to examine adults (≥18) with a reported history of ACEs, self-reported and/or diagnosed anxiety, and chronic pain. The SLR included quality appraisal according to the Joanna Briggs Institute tool. RESULTS: The narrative summary indicated a significant association between ACEs, anxiety, and chronic pain experiences in adults. Of 52 selected studies, 79% reported a moderate-strong association. For ACE prevalence, the majority reported experiencing sexual abuse (50% [SD 16.01]), followed by physical abuse (46% [SD 20.7]). Other ACEs included emotional abuse (33% [SD 17.17]), emotional neglect (25% [SD 21.02]), and physical neglect (23% [SD 22.44]). Meta-analyses showed moderate associations between anxiety and chronic pain (r = 0.30; 95% CI = [0.14, 0.45], p < 0.01) and between ACEs and anxiety (r = 0.26; 95% CI = [0.15, 0.36], p < 0.01), and that participants who experienced ACEs are around twice as likely to present chronic pain during adulthood (OR = 1.99; 95% CI = [1.53, 2.60], p < 0.01). CONCLUSION: The results of the SLR and meta-analysis indicated that ACEs and anxiety influence chronic pain experience in adults. Given the relationship between ACEs and anxiety, there would be value in exploring this as a potential mediator in future studies. SIGNIFICANCE: There was an unmet need to summarize the existing literature on the relationship between ACEs and anxiety on chronic pain experience in adults and the association between ACEs and anxiety. The results of this systematic review and meta-analysis indicated that both ACEs and anxiety influenced chronic pain experience in adults and helped to inform the diverse literature on these potential relationships to date.