Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability.

BACKGROUND: Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years. METHODS: Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate. RESULTS: Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability. CONCLUSION: Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.

Gender-specific aspects of socialisation and risk of cardiovascular disease among community-dwelling older adults: a prospective cohort study using machine learning algorithms and a conventional method.

BACKGROUND: Gender influences cardiovascular disease (CVD) through norms, social relations, roles and behaviours. This study identified gender-specific aspects of socialisation associated with CVD. METHODS: A longitudinal study was conducted, involving 9936 (5,231 women and 4705 men) initially healthy, community-dwelling Australians aged 70 years or more from the ASPirin in Reducing Events in the Elderly (ASPREE) study and ASPREE Longitudinal Study of Older Persons, with a median follow-up time of 6.4 years. Variable categorisation, variable selection (using machine learning (ML) models; Elastic Net and extreme gradient boosting) and Cox-regression were employed separately by binary gender to identity socialisation factors (n=25 considered) associated with CVD. RESULTS: Different socialisation factors were identified using the ML models. In the Cox model, for both genders, being married/partnered was associated with a reduced risk of CVD (men: HR 0.76, 95% CI 0.60 to 0.96; women: HR 0.67, 95% CI 0.58 to 0.95). For men, having 3-8 relatives they felt close to and could call on for help (HR 0.76, 95% CI 0.58 to 0.99; reference <3 relatives), having 3-8 relatives they felt at ease talking with about private matters (HR 0.70, 95% CI 0.55 to 0.90; reference <3 relatives) or playing games such as chess or cards (HR 0.82, 95% CI 0.67 to 1.00) was associated with reduced risk of CVD. For women, living with others (HR 0.71, 95% CI 0.55 to 0.91) or having ≥3 friends they felt at ease talking with about private matters (HR 0.74, 95% CI 0.58 to 0.95; reference <3 friends) was associated with a lower risk of CVD. CONCLUSIONS: This study demonstrates the need to prioritise gender-specific social factors to improve cardiovascular health in older adults.

Sex differences in biological aging and the association with clinical measures in older adults.

Females live longer than males, and there are sex disparities in physical health and disease incidence. However, sex differences in biological aging have not been consistently reported and may differ depending on the measure used. This study aimed to determine the correlations between epigenetic age acceleration (AA), and other markers of biological aging, separately in males and females. We additionally explored the extent to which these AA measures differed according to socioeconomic characteristics, clinical markers, and diseases. Epigenetic clocks (HorvathAge, HannumAge, PhenoAge, GrimAge, GrimAge2, and DunedinPACE) were estimated in blood from 560 relatively healthy Australians aged ≥ 70 years (females, 50.7%) enrolled in the ASPREE study. A system-wide deficit accumulation frailty index (FI) composed of 67 health-related measures was generated. Brain age and subsequently brain-predicted age difference (brain-PAD) were estimated from neuroimaging. Females had significantly reduced AA than males, but higher FI, and there was no difference in brain-PAD. FI had the strongest correlation with DunedinPACE (range r: 0.21 to 0.24 in both sexes). Brain-PAD was not correlated with any biological aging measures. Significant correlations between AA and sociodemographic characteristics and health markers were more commonly found in females (e.g., for DunedinPACE and systolic blood pressure r = 0.2, p < 0.001) than in males. GrimAA and Grim2AA were significantly associated with obesity and depression in females, while in males, hypertension, diabetes, and chronic kidney disease were associated with these clocks, as well as DunedinPACE. Our findings highlight the importance of considering sex differences when investigating the link between biological age and clinical measures.

The Role of Social Determinants of Health in Cardiovascular Diseases: An Umbrella Review.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Addressing social determinants of health (SDoH) may be the next forefront of reducing the enormous burden of CVD. SDoH can be defined as any social, economic, or environmental factor that influences a health outcome. Comprehensive evidence of the role of SDoH in CVD is lacking, nevertheless. This umbrella review aims to give a comprehensive overview of the role of SDoH in CVD. We searched systematic reviews (with or without meta-analyses) using 8 databases and included review reference lists. Four themes (economic circumstances, social/community context, early childhood development, and neighbourhood/built environment) and health literacy in the health/health care theme were considered. Seventy reviews were eligible. Despite the quality of the included reviews being low or critically low, there was consistent evidence that factors relating to economic circumstances and early childhood development themes were associated with an increased risk of CVD and CVD mortality. We also found evidence that factors in the social/community context and neighbourhood/built environment themes, such as social isolation, fewer social roles, loneliness, discrimination, ethnicity, neighborhood socioeconomic status, violence, and environmental attributes, had a role in CVD. SDoH factors without (or with minimal) evidence synthesis for CVD were also identified. In sum, this umbrella review offers evidence that SDoH, especially economic circumstance and early childhood development, play a significant role in CVD. This calls for the strengthening of nonmedical interventions that address multiple factors simultaneously and the inclusion of SDoH in future CVD risk prediction models. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022346994.

Lifetime posttraumatic stress disorder as a predictor of mortality: a systematic review and meta-analysis.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) could potentially increase the risk of mortality, and there is a need for a meta-analysis to quantify this association. This study aims to determine the extent to which PTSD is a predictor of mortality. METHODS: EMBASE, MEDLINE, and PsycINFO were searched systematically on 12th February 2020, with updated searches conducted in July 2021, and December 2022 (PROSPERO CRD42019142971). Studies involving community-dwelling participants with a diagnosis of PTSD or PTSD symptoms, and a comparator group of individuals without PTSD, and which assessed mortality risk, were included. A random-effects meta-analysis was conducted on studies reporting Odds Ratio (OR), Hazard Ratio (HR), and Risk Ratio (RR), and subgroup analysis was also performed by age, sex, type of trauma experienced, PTSD diagnosis, and cause of death. RESULTS: A total of 30 eligible studies of mostly good methodological quality were identified, with a total of more than 2.1 million participants with PTSD. The majority of studies involved male-dominated, veteran populations. PTSD was associated with a 47% (95% CI: 1.06-2.04) greater risk of mortality across six studies that reported OR/RR, and a 32% increased risk across 18 studies which reported time to death (HR: 1.32, 95% CI: 1.10-1.59). There was very high study heterogeneity (I2 > 94%) and this was not explained by the prespecified subgroup analysis. CONCLUSION: PTSD is associated with increased mortality risk, however further research is required amongst civilians, involving women, and in individuals from underdeveloped countries.

The relationship between social isolation, social support, and loneliness with cardiovascular disease and shared risk factors: A narrative review.

BACKGROUND: Cardiovascular disease (CVD) is the greatest contributor to global morbidity and mortality. Poor social health plays a critical role in CVD incidence. Additionally, the relationship between social health and CVD may be mediated through CVD risk factors. However, the underlying mechanisms between social health and CVD are poorly understood. Certain social health constructs (social isolation, low social support and loneliness) have complicated the characterisation of a causal relationship between social health and CVD. AIM: To provide an overview of the relationship between social health and CVD (and its shared risk factors). METHOD: In this narrative review, we examined published literature on the relationship between three social health constructs (social isolation, social support, and loneliness) and CVD. Evidence was synthesised in a narrative format, focusing on the potential ways in which social health affects CVD, including shared risk factors. RESULTS: The current literature highlights an established relationship between social health and CVD with a likelihood for bi-directionality. However, there is speculation and varied evidence regarding how these relationships may be mediated through CVD risk factors. CONCLUSIONS: Social health can be considered an established risk factor for CVD. However, the potential bi-directional pathways of social health with CVD risk factors are less established. Further research is needed to understand whether targeting certain constructs of social health may directly improve the management of CVD risk factors. Given the health and economic burdens of poor social health and CVD, improvements to addressing or preventing these interrelated health conditions would have societal benefits.

Social Isolation and Social Support Influence Health Service Utilisation and Survival after a Cardiovascular Disease Event: A Systematic Review.

Both cardiovascular disease (CVD) and social health carry high health and economic burdens. We undertook a systematic review to investigate the association between social isolation, low social support, and loneliness with health service utilisation and survival after a CVD event among people living in Australia and New Zealand. Four electronic databases were systematically searched for the period before June 2020. Two reviewers undertook the title/abstract screen. One reviewer undertook a full-text screen and data extraction. A second author checked data extraction. Of 756 records, 25 papers met our inclusion criteria. Included studies recruited 10-12,821 participants, aged 18-98 years, and the majority were males. Greater social support was consistently associated with better outcomes on four of the five themes (discharge destination, outpatient rehabilitation attendance, rehospitalisation and survival outcomes; no papers assessed the length of inpatient stay). Positive social health was consistently associated with better discharge designation to higher independent living. As partner status and living status did not align with social isolation and social support findings in this review, we recommend they not be used as social health proxies. Our systematic review demonstrates that social health is considered in cardiac care decisions and plays a role in how healthcare is being delivered (i.e., outpatient, rehabilitation, or nursing home). This likely contributes to our finding that lower social support is associated with high-intensity healthcare services, lower outpatient rehabilitation attendance, greater rehospitalisation and poorer survival. Given our evidence, the first step to improve cardiac outcomes is acknowledging that social health is part of the decision-making process. Incorporating a formal assessment of social support into healthcare management plans will likely improve cardiac outcomes and survival. Further research is required to assess if support person/s need to engage in the risk reduction behaviours themselves for outpatient rehabilitation to be effective. Further synthesis of the impact of social isolation and loneliness on health service utilisation and survival after a CVD event is required.

Are social isolation, lack of social support or loneliness risk factors for cardiovascular disease in Australia and New Zealand? A systematic review and meta-analysis.

BACKGROUND: An international systematic review concluded that individuals with poor social health (social isolation, lack of social support or loneliness) are 30% more likely to develop coronary heart disease (CHD) and stroke. Notably, the two included Australian papers reported no association between social health and CHD or stroke. OBJECTIVE: We undertook a systematic review and meta-analysis to investigate the association between social isolation, lack of social support and loneliness and cardiovascular disease (CVD) incidence among people living in Australia and New Zealand. METHODS: Four electronic databases were systematically searched for longitudinal studies published until June 2020. Two reviewers undertook title/abstract screen and one reviewer undertook full-text screen and data extraction. Quality was assessed using the Newcastle - Ottawa Quality Assessment Scale. RESULTS: Of the 725 unique records retrieved, five papers met our inclusion criteria. These papers reported data from three Australian longitudinal datasets, with a total of 2137 CHD and 590 stroke events recorded over follow-up periods ranging from 3 to 16 years. Reports of two CHD and two stroke outcomes were suitable for meta-analysis. The included papers reported no association between social health and incidence of CVD in all fully adjusted models and most unadjusted models. CONCLUSIONS: Our systematic review is inconclusive as it identified only a few studies, which relied heavily on self-reported CVD. Further studies using medical diagnosis of CVD, and assessing the potential influence of residential remoteness, are needed to better understand the relationship between social health and CVD incidence in Australia and New Zealand.

Trajectories of physical health-related quality of life and the risk of incident cardiovascular disease events and all-cause mortality in older people.

Study objective: The aim of this study was to identify whether physical component score (PCS) of health-related quality of life trajectories over 4.7-years predicted subsequent risk of incident fatal and non-fatal CVD events, and all-cause mortality. Methods: This study included 16,871 community-dwelling people aged ≥65 years enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) trial. PCS was assessed annually using the SF-12 (version-2) over a median 4.7-years (i.e. from baseline (2010-2014) till June 2017). Incident CVD events and all-cause mortality occurring after June 2017 until the second-year after the end of the trial were considered. Growth mixture and logistic regression modelling were used. Results: Four PCS trajectories were identified: high (66.5%), intermediate (13.3%), decline (13.8%), and low (6.5%), and there was subsequently a total of 406 (2.50%) incident CVD events, 197 (1.17%) fatal CVD, and 751 (4.45%) deaths. The declining PCS trajectory group had the highest risk of incident CVD (adjusted OR, 1.51; 95% CI 1.14, 1.99), while the low PCS trajectory group had the greatest risk of fatal CVD (adjusted OR, 1.74; 95%CI 1.06, 2.85) and all-cause mortality (adjusted OR, 1.83; 95%CI 1.40, 2.40). After further adjustment for the baseline PCS score, only the association between declining PCS trajectory and incident CVD (adjusted OR, 1.51; 95%CI 1.11, 2.07) remained. Conclusion: Our study strengthens the importance of PCS as a predictive measure of CVD and all-cause mortality in older people and also highlights that a declining PCS trajectory could be considered an early predictor of future CVD events.

Does social isolation, social support or loneliness influence health or well-being after a cardiovascular disease event? A narrative thematic systematic review.

Identification of factors which influence health after a cardiovascular disease (CVD) event will assist with reducing the high health and economic burden of CVD. We undertook a systematic review to investigate the association between social health (lower social isolation, higher social support and lower loneliness) and health and well-being after a CVD event among people living in Australia and New Zealand. Four electronic databases were systematically searched until June 2020. Two reviewers undertook title/abstract screen. One reviewer undertook full-text screen and data extraction. A second author either independently extracted or checked data. Narrative thematic analysis was undertaken. Of the 752 unique records retrieved, 39 papers from 29 studies met our inclusion criteria. Included studies recruited between 10 and 1,455 participants, aged 12-96 years, and the majority were male. Greater social health was consistently associated with better mental health outcomes (lower depressive symptoms, anxiety symptoms and psychological distress). Lower social isolation and higher social support were associated with the extent to which patient needs were being met. Living situation was not associated with mental health outcomes, and being married or living with someone was associated with greater medication adherence. Our systematic review demonstrates that greater social health is associated with better mental health outcomes and met patient needs among cardiac patients. As partner status and living status did not align with social isolation and social support findings in this review, we recommend they not be used as social health proxies when assessing health outcomes among CVD patients. Our review highlights the need for more research focused on women and the importance of gender-disaggregated reporting. Further assessment is required to evaluate whether loneliness is associated with health and well-being outcomes after a CVD event.

Impact of economic factors, social health and stressful life events on physical health-related quality of life trajectories in older Australians.

PURPOSE: Physical health-related quality of life (HRQoL) is associated with adverse health outcomes, including hospitalizations and all-cause mortality. However, little is known about how physical HRQoL changes over time in older people and the predictors of this trajectory. This study (a) identified trajectories of physical HRQoL among older people and (b) explored whether economic factors, social health or stressful life events impact physical HRQoL trajectories. METHOD: A cohort of 12,506 relatively 'healthy' community-dwelling Australians aged ≥ 70 years (54.4% females), enrolled in the ASPREE Longitudinal Study of Older Persons (ALSOP) study and was followed for six years. Economic factors, social health and life events in the last 12 months were assessed through a questionnaire at baseline. Physical HRQoL was measured by using the 12-item short form at baseline and annual follow-ups. Growth mixture and structural equation modelling were used to identify physical HRQoL trajectories and their predictors. RESULTS: Four physical HRQoL trajectories were identified-stable low (7.1%), declining (9.0%), stable intermediate (17.9%) and stable high (66.0%). Living in more disadvantaged areas, having a lower household income, no paid work, no voluntary work, loneliness and stressful life events (i.e. spousal illness, friend/family illness, financial problem) were associated with a 10%-152% higher likelihood of being in the stable low or declining physical HRQoL trajectory than the stable high group. CONCLUSION: Specific stressful life events had a greater impact on adverse physical HRQoL trajectories in older people than other factors. Volunteering may prevent physical HRQoL decline and requires further investigation.

Health-related quality of life and incident cardiovascular disease events in community-dwelling older people: A prospective cohort study.

BACKGROUND: Lower health-related quality of life (HRQoL) has been shown to predict a higher risk of hospital readmission and mortality in patients with cardiovascular disease (CVD). Few studies have explored the associations between HRQoL and incident CVD. We explored the associations between baseline HRQoL and incident and fatal CVD in community-dwelling older people in Australia and the United States. METHODS: Longitudinal study using ASPirin in Reducing Events in the Elderly (ASPREE) trial data. This includes 19,106 individuals aged 65-98 years, initially free of CVD, dementia, or disability, and followed between March 2010 and June 2017. The physical (PCS) and mental component scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Incident major adverse CVD events included fatal CVD (death due to atherothrombotic CVD), hospitalizations for heart failure, myocardial infarction or stroke. Analyses were performed using Cox proportional-hazard regression. RESULTS: Over a median 4.7 follow-up years, there were 922 incident CVD events, 203 fatal CVD events, 171 hospitalizations for heart failure, 355 fatal or nonfatal myocardial infarction and 403 fatal or nonfatal strokes. After adjustment for sociodemographic, health-related behaviours and clinical measures, a 10-unit higher PCS, but not MCS, was associated with a 14% lower risk of incident CVD, 28% lower risk of hospitalization for heart failure and 15% lower risk of myocardial infarction. Neither PCS nor MCS was associated with fatal CVD events or stroke. CONCLUSION: Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older individuals.

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia.

BACKGROUND: Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population. OBJECTIVE: We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences. METHODS: 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65-98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010-2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively. RESULTS: At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender. CONCLUSION: Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling older people.

Health-related quality of life and all-cause mortality among older healthy individuals in Australia and the United States: a prospective cohort study.

PURPOSE: Previous research has demonstrated that lower health-related quality of life (HRQoL) is associated with higher morbidity and mortality, especially in-patient groups. The association of HRQoL with all-cause mortality in community samples requires further investigation. This study aimed to examine whether HRQoL predicts all-cause mortality in older healthy community-dwelling people from Australia and the United States (U.S.) enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial. We also explored whether this association varies by gender or country. METHOD: A prospective cohort of 19,106 individuals aged 65-98 years, who were without a dementia diagnosis or a known major life-limiting disease, and completed the 12-item short-form-HRQoL at recruitment (2010-2014). They were followed until June 2017. Cox proportional-hazard models were used to determine the association between the physical (PCS) and mental component scores (MCS) of HRQoL and all-cause mortality, adjusting for sociodemographic factors, health-related behaviours and clinical measures. Hazards ratios were estimated for every 10-unit increase in PCS or MCS. RESULTS: There were 1052 deaths over a median 4.7-years (interquartile range 3.6-5.7) of follow-up, with 11.9 events per 1000 person-years. Higher PCS was associated with lower all-cause mortality (HR 0.83, 95% CI 0.77, 0.89) in the entire sample, while higher MCS was associated with lower mortality among U.S. participants only (HR 0.78, 95% CI 0.63, 0.95). Gender differences in the association of either PCS or MCS with mortality were not observed. CONCLUSION: Our large study provides evidence that HRQoL is inversely associated with all-cause mortality among initially healthy older people.

Distinct Cognitive Trajectories in Late Life and Associated Predictors and Outcomes: A Systematic Review.

BACKGROUND: Cognitive aging is a dynamic process in late life with significant heterogeneity across individuals. OBJECTIVE: To review the evidence for latent classes of cognitive trajectories and to identify the associated predictors and outcomes. METHODS: A systematic search was performed in MEDLINE and EMBASE for articles that identified two or more cognitive trajectories in adults. The study was conducted following the PRISMA statement. RESULTS: Thirty-seven studies were included, ranging from 219 to 9,704 participants, with a mean age of 60 to 93.4 years. Most studies (n = 30) identified distinct cognitive trajectories using latent class growth analysis. The trajectory profile commonly consisted of three to four classes with progressively decreasing baseline and increasing rate of decline-a 'stable-high' class characterized as maintenance of cognitive function at high level, a 'minor-decline' class or 'stable-medium' class that declines gradually over time, and a 'rapid-decline' class with the steepest downward slope. Generally, membership of better classes was predicted by younger age, being female, more years of education, better health, healthier lifestyle, higher social engagement and lack of genetic risk variants. Some factors (e.g., education) were found to be associated with cognitive function over time only within individual classes. CONCLUSION: Cognitive aging in late life is a dynamic process with significant inter-individual variability. However, it remains unclear whether similar patterns of cognitive aging are observed across all cognitive domains. Further research into unique factors which promote the maintenance of high-cognitive function is needed to help inform public policy.

Quality of life and mortality in the general population: a systematic review and meta-analysis.

BACKGROUND: Quality of life (QoL) is multi-dimensional concept of an individual' general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. METHODS: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. RESULTS: Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992). CONCLUSION: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.

Differential multiple sclerosis treatment allocation between Australia and New Zealand associated with clinical outcomes but not mood or quality of life.

BACKGROUND: Differential treatment allocation may impact on clinical phenotype in MS and in turn upon quality of life (QoL). OBJECTIVES: (a) Investigate the association between disease-modifying drugs (DMDs) use and relapse frequency, disability, clinically significant fatigue, and physical and mental health-related QoL among participants with MS residing in Australia and New Zealand (NZ); (b) assess whether these associations differed between Australia and NZ. METHODS: Disability and fatigue were measured by PDDS and FSS, respectively. QoL was assessed by MSQOL-54. Associations were assessed by binomial and multinomial logistic regression, as appropriate. Multivariable models were adjusted for demographic and clinical covariates, as appropriate. RESULTS: 837 participants (627 from Australia; 210 from NZ) were identified from an online cohort of people with MS. First- and second-generation DMD use was associated with higher adjusted-odds of fatigue and disability, though not with 12-month relapse number. DMD use was not independently associated with physical or mental QoL. The association of first-generation DMD use with moderate disability differed between nations, such that treatment was associated with lower odds in Australia but not in NZ; a similar but a small difference was found for severe disability. No differences were seen in the DMD association with relapse number, nor with fatigue or QoL, between Australia and NZ. CONCLUSION: The differential treatment allocation associations in NZ are evident in the DMD-disability association, but there is no evidence that this treatment regimen has negative associations with fatigue, mood, or QoL.

The Efficacy of Psychological Interventions for Managing Fatigue in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system. Fatigue is commonly reported by people with MS (PwMS). MS-related fatigue severely affects daily activities, employment, socioeconomic status, and quality of life. OBJECTIVE: We conducted this systematic review and meta-analysis to determine whether psychological interventions are effective in managing fatigue in PwMS. DATA SOURCES: We performed systematic searches of Medline, EMBASE, PsycINFO, and CINAHL to identify relevant articles published from database inception to April 5, 2017. Reference lists from relevant reviews were also searched. STUDY SELECTION AND DESIGN: Two independent reviewers screened the papers, extracted data, and appraised the included studies. A clinical psychologist verified whether interventions were psychological approaches. A narrative synthesis was conducted for all included studies. For relevant randomized controlled trials that reported sufficient information to determine standardized mean differences (SMDs) and 95% confidence intervals (CIs), meta-analyses were conducted using a random-effects model. RESULTS: Of the 353 identified articles, 20 studies with 1,249 PwMS were included in this systematic review. Narrative synthesis revealed that psychological interventions reduced fatigue in PwMS. Meta-analyses revealed that cognitive behavioral therapy decreased levels of fatigue compared with non-active controls (SMD = -0.32; 95% CI: -0.63 to -0.01) and compared with active controls (relaxation or psychotherapy) (SMD = -0.71; 95% CI: -1.05 to -0.37). Meta-analyses further showed that both relaxation (SMD = -0.90; 95% CI: -1.30 to -0.51), and mindfulness interventions (SMD = -0.62; 95% CI: -1.12 to -0.12), compared with non-active control, decreased fatigue levels. The estimates of heterogeneity for the four meta-analyses varied between none and moderate. CONCLUSION: This study found that the use of psychological interventions for MS-related fatigue management reduced fatigue in PwMS. While psychological interventions are generally considered first-line therapy for MS-related fatigue, further studies are needed to explore the long-term effect of this therapy.