Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.

BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. OBJECTIVE: To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. METHODS: A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. RESULTS: From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. CONCLUSION: An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.

Identifying longitudinal healthcare pathways and subsequent mortality for people living with dementia in England: an observational group-based trajectory analysis.

BACKGROUND: The number of people living with dementia (PLWD) continues to increase, particularly those with severe symptomatology. Severe symptoms and greater ill-health result in more acute care need. Early healthcare interventions can prove beneficial. Healthcare use has not been analysed as a holistic set of interlinked events. This study explores different healthcare pathways among PLWD, social or spatial inequalities in healthcare pathways and subsequent mortality risk. METHODS: Group-based trajectory models (GBTM) were applied to electronic healthcare records. We generated clusters of PLWD with similar five-year, post-diagnosis trajectories in rates of primary and secondary healthcare use. Potential social and spatial variations in healthcare use clusters were examined. Cox Proportional Hazards used to explore variation in subsequent mortality risk between healthcare use clusters. RESULTS: Four healthcare use clusters were identified in both early- (n = 3732) and late-onset (n = 6224) dementia populations. Healthcare use variations were noted; consistent or diminishing healthcare use was associated with lower subsequent mortality risk. Increasing healthcare use was associated with increased mortality risk. Descriptive analyses indicated social and spatial variation in healthcare use cluster membership. CONCLUSION: Healthcare pathways can help indicate changing need and variation in need, with differential patterns in initial healthcare use post-diagnosis, producing similar subsequent mortality risk. Care in dementia needs to be more accessible and appropriate, with care catered to specific and changing needs. Better continuity of care and greater awareness of dementia in primary can enhance prospects for PLWD. Research needs to further illuminate holistic care need for PLWD, including health and social care use, inequalities in care, health and outcomes.

Pharmacist-led intervention for older people with atrial fibrillation in long-term care (PIVOTALL study): a randomised pilot and feasibility study.

BACKGROUND: Older care home residents are a vulnerable group of people with atrial fibrillation (AF) at high risk of adverse health events. The Atrial Fibrillation Better Care (ABC: Avoid stroke; Better symptom management; Cardiovascular and other comorbidity management) pathway is the gold-standard approach toward integrated AF care, and pharmacists are a potential resource with regards to its' implementation. The aim of this study was to determine the feasibility of pharmacist-led medicines optimisation in care home residents, based on the ABC pathway compared to usual care. METHODS: Individually randomised, prospective pilot and feasibility study of older (aged ≥ 65 years) care home residents with AF (ISRCTN14747952); residents randomised to ABC pathway optimised care versus usual care. The primary outcome was a description of study feasibility (resident and care home recruitment and retention). Secondary outcomes included the number and type of pharmacist medication recommendations and general practitioner (GP) implementation. RESULTS: Twenty-one residents were recruited and 11 (mean age [standard deviation] 85.0 [6.5] years, 63.6% female) were randomised to receive pharmacist-led medicines optimisation. Only 3/11 residents were adherent to all three components of the ABC pathway. Adherence was higher to 'A' (9/11 residents) and 'B' (9/11 residents) components compared to 'C' (3/11 residents). Four ABC-specific medicines recommendations were made for three residents, and two were implemented by residents' GPs. Overall ABC adherence rates did not change after pharmacist medication review, but adherence to 'A' increased (from 9/11 to 10/11 residents). Other ABC recommendations were inappropriate given residents' co-morbidities and risk of medication-related adverse effects. CONCLUSIONS: The ABC pathway as a framework was feasible to implement for pharmacist medication review, but most residents' medications were already optimised. Low rates of adherence to guideline-recommended therapy were a result of active decisions not to treat after assessment of the net risk-benefit.

Social and spatial inequalities in healthcare use among people living with dementia in England (2002-2016).

OBJECTIVES: Healthcare services for people living with dementia (PLWD) are stretched, and government promises of increased funding remain undelivered. With the UK dementia population to surpass 1 million by 2024, and dementia care costs predicted to almost treble by 2040, it is essential we understand differences in healthcare use among PLWD. This study aimed to explore social and spatial variations in healthcare use among people diagnosed with dementia (2002-2016). METHODS: Data were derived from Electronic Health Records of Clinical Practice Research Datalink GP patients in England (n = 142,302). To standardise healthcare contacts, rates of healthcare contacts per year were calculated for three primary (GP observations and medications) and three secondary healthcare types [Accident & Emergency (A&E) attendances and, emergency and elective hospital admissions]. Fully-adjusted generalised linear regression models were used to identify healthcare use variation by social and spatial groups. Twelve models were generated, one for each healthcare type in early- and late-onset populations separately. RESULTS: This study highlights numerous social and spatial variations in healthcare use among PLWD. Among PLWD, several groups tended to have healthcare service use more closely associated with negative outcomes, including a greater likelihood of A&E attendances and emergency and elective hospital admissions. These groups include: men, people from White ethnicity groups and people from more deprived and rural areas. CONCLUSIONS: Systemic and social measures are needed to reduce variations in healthcare use inequalities in PWLD. These include greater healthcare continuity, health checks and medicines reviews, culturally appropriate services, better and more accessible treatment and improved infrastructure.

Treatment priorities and regret in older adults with head and neck cancer: A systematic review.

BACKGROUND: The majority of head and neck cancer (HNC) diagnoses are seen in people aged 70 and older; these numbers are set to increase. Greater understanding of treatment needs of older patients with HNC is essential. These older patients often have co-existing health conditions, are prone to frailty and may not prioritise survival when considering treatment options. This systematic review examines the current research with regard to priorities and factors influencing treatment regret in older people with HNC. METHODS: Studies were eligible for inclusion if they (i) reported data from patients with a mean age of 65 years or older who had a confirmed diagnosis of HNC and had been treated using surgery, chemotherapy and/or radiotherapy with either palliative or curative intent, (ii) considered patient's priorities or preferences or examined treatment regret as one of the primary outcomes of the study (iii) were published in English. RESULTS: Pilot search identified n = 7222 articles; however, following screening, only four papers met the inclusion criteria. Narrative synthesis was indicated to analyse quantitative and qualitative evidence in parallel, as meta-analyses were not possible. DISCUSSION: There is a paucity in the literature examining older adults with HNC. There is an indication that older adults prioritise maintaining independence when making treatment decisions and treatment regret is seen in those with high levels of depression with level of frailty also a contributing factor. Clinicians should consider patient's social circumstances, premorbid status and priorities in maintaining independence and managing symptoms when making treatment decisions in this cohort.

Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.

OBJECTIVE: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. METHODS: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. RESULTS: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001). CONCLUSIONS: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.

Reducing hospital admissions in older care home residents: a 4-year evaluation of the care home innovation Programme (CHIP).

BACKGROUND: Older care home residents frequently attend emergency departments with a high conversion to admissions. For this purpose, a novel Care Home Innovation Programme (CHIP) was introduced with the aim of reducing potentially avoidable hospital admissions by 30%. The aim of this study is to evaluate the implementation of this innovative service in practice. METHODS: A total of 32 care homes with 1314 beds in South Sefton, Merseyside were invited to sign up to CHIP which was launched in April 2015 and continued in its entirety until June 2018. As part of the CHIP, care home matrons were introduced, new protocols were developed to address common presentations, a 24-h 7-day a week televideo system installed across all homes, and a quarterly training collaborative brought care homes together to learn and share good practices together. Data on emergency calls and calls resulting in conveyances were recorded over a four-year period, and analysed using frequency analysis. RESULTS: In comparison to the 12 months prior to launch, over a four-year period, implementation of the CHIP resulted in a 15% reduction of emergency calls, and in a 19% reduction of conveyances to hospital. CONCLUSIONS: The South Sefton CHIP demonstrated itself an effective programme in reducing conveyances and consequently, hospital admissions of care home residents. This model will be superseded by the enhanced health in care homes being promoted by the NHS Long Term Care Plan.

Standard set of health outcome measures for older persons.

BACKGROUND: The International Consortium for Health Outcomes Measurement (ICHOM) was founded in 2012 to propose consensus-based measurement tools and documentation for different conditions and populations.This article describes how the ICHOM Older Person Working Group followed a consensus-driven modified Delphi technique to develop multiple global outcome measures in older persons. The standard set of outcome measures developed by this group will support the ability of healthcare systems to improve their care pathways and quality of care. An additional benefit will be the opportunity to compare variations in outcomes which encourages and supports learning between different health care systems that drives quality improvement. These outcome measures were not developed for use in research. They are aimed at non researchers in healthcare provision and those who pay for these services. METHODS: A modified Delphi technique utilising a value based healthcare framework was applied by an international panel to arrive at consensus decisions.To inform the panel meetings, information was sought from literature reviews, longitudinal ageing surveys and a focus group. RESULTS: The outcome measures developed and recommended were participation in decision making, autonomy and control, mood and emotional health, loneliness and isolation, pain, activities of daily living, frailty, time spent in hospital, overall survival, carer burden, polypharmacy, falls and place of death mapped to a three tier value based healthcare framework. CONCLUSIONS: The first global health standard set of outcome measures in older persons has been developed to enable health care systems improve the quality of care provided to older persons.

New insights into healthy ageing, inflammageing and frailty using metabolomics.

Human ageing is a normal process and does not necessarily result in the development of frailty. A mix of genetic, environmental, dietary, and lifestyle factors can have an impact on ageing, and whether an individual develops frailty. Frailty is defined as the loss of physiological reserve both at the physical and cellular levels, where systemic processes such as oxidative stress and inflammation contribute to physical decline. The newest "omics" technology and systems biology discipline, metabolomics, enables thorough characterisation of small-molecule metabolites in biological systems at a particular time and condition. In a biological system, metabolites-cellular intermediate products of metabolic reactions-reflect the system's final response to genomic, transcriptomic, proteomic, epigenetic, or environmental alterations. As a relatively newer technique to characterise metabolites and biomarkers in ageing and illness, metabolomics has gained popularity and has a wide range of applications. We will give a comprehensive summary of what is currently known about metabolomics in studies of ageing, with a focus on biomarkers for frailty. Metabolites related to amino acids, lipids, carbohydrates, and redox metabolism may function as biomarkers of ageing and/or frailty development, based on data obtained from human studies. However, there is a complexity that underpins biological ageing, due to both genetic and environmental factors that play a role in orchestrating the ageing process. Therefore, there is a critical need to identify pathways that contribute to functional decline in people with frailty.

Frailty: a global health challenge in need of local action.

Frailty is a complex, age-related clinical condition that involves multiple contributing factors and raises the risk of adverse outcomes in older people. Given global population ageing trends, the growing prevalence and incidence of frailty pose significant challenges to health and social care systems in both high-income and lower-income countries. In this review, we highlight the disproportionate representation of research on frailty screening and management from high-income countries, despite how lower-income countries are projected to have a larger share of older people aged ≥60. However, more frailty research has been emerging from lower-income countries in recent years, paving the way for more context-specific guidelines and studies that validate frailty assessment tools and evaluate frailty interventions in the population. We then present further considerations for contextualising frailty in research and practice in lower-income countries. First, the heterogeneous manifestations of frailty call for research that reflects different geographies, populations, health systems, community settings and policy priorities; this can be driven by supportive collaborative systems between high-income and lower-income countries. Second, the global narrative around frailty and ageing needs re-evaluation, given the negative connotations linked with frailty and the introduction of intrinsic capacity by the World Health Organization as a measure of functional reserves throughout the life course. Finally, the social determinants of health as possible risk factors for frailty in lower-income countries and global majority populations, and potential socioeconomic threats of frailty to national economies warrant proactive frailty screening in these populations.

Nitric oxide releasing coatings for the prevention of viral and bacterial infections.

Healthcare associated infections (HCAI) represent a significant burden worldwide contributing to morbidity and mortality and result in substantial economic consequences equating to billions annually. Although the impacts of HCAI have been felt for many years, the coronavirus pandemic has had a profound effect, escalating rates of HCAI, even with extensive preventative measures such as vaccination, personal protective equipment, and deep cleaning regimes. Therefore, there is an urgent need for new solutions to mitigate this serious health emergency. In this paper, the fabrication of nitric oxide (NO) releasing dual action polymer coatings for use in healthcare applications is described. The coatings are doped with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and release high payloads of NO in a sustained manner for in excess of 50 hours. These coatings are extensively characterized in multiple biologically relevant solutions and the antibacterial/antiviral efficacy is studied. For the first time, we assess antibacterial activity in a time course study (1, 2, 4 and 24 h) in both nutrient rich and nutrient poor conditions. Coatings exhibit excellent activity against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA), with up to complete reduction observed over 24 hours. Additionally, when tested against SARS-CoV-2, the coatings significantly reduced active virus in as little as 10 minutes. These promising results suggest that these coatings could be a valuable addition to existing preventative measures in the fight against HCAIs.

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

INTRODUCTION: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. METHODS: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. RESULTS: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). CONCLUSION: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Managing older people with atrial fibrillation and preventing stroke: a review of anticoagulation approaches.

INTRODUCTION: Oral anticoagulants (OACs) are the cornerstone of stroke prevention in atrial fibrillation (AF), but prescribing decisions in older people are complicated. Clinicians must assess the net clinical benefit of OAC in the context of multiple chronic conditions, polypharmacy, frailty and life expectancy. The under-representation of high-risk, older adult sub-populations in clinical trials presents the challenge of choosing the right OAC, where a 'one-size-fits-all' approach cannot be taken. AREAS COVERED: This review discusses OAC approaches for stroke prevention in older people with AF and presents a prescribing aid to support clinicians' decision-making. High-risk older adults with multiple chronic conditions, specifically chronic kidney disease, dementia/cognitive impairment, previous stroke/transient ischemic attack or intracranial hemorrhage, polypharmacy, frailty, low body weight, high falls risk, and those aged ≥75 years are considered. EXPERT OPINION: Non-vitamin K antagonist OACs are the preferred first-line OAC in older adults with AF, including high-risk subpopulations, after individual assessment of stroke and bleeding risk, except those with mechanical heart valves and moderate-to-severe mitral stenosis. Head-to-head comparisons of NOACs are not available, therefore the choice of drug (and dose) should be based on an individual's risk (stroke and bleeding) and incorporate their treatment preferences. Treatment decisions must be person-centered and principles of shared decision-making applied.

General Framework to Quantitatively Predict Pharmacokinetic Induction Drug-Drug Interactions Using In Vitro Data.

INTRODUCTION: Metabolic inducers can expose people with polypharmacy to adverse health outcomes. A limited fraction of potential drug-drug interactions (DDIs) have been or can ethically be studied in clinical trials, leaving the vast majority unexplored. In the present study, an algorithm has been developed to predict the induction DDI magnitude, integrating data related to drug-metabolising enzymes. METHODS: The area under the curve ratio (AUCratio) resulting from the DDI with a victim drug in the presence and absence of an inducer (rifampicin, rifabutin, efavirenz, or carbamazepine) was predicted from various in vitro parameters and then correlated with the clinical AUCratio (N = 319). In vitro data including fraction unbound in plasma, substrate specificity and induction potential for cytochrome P450s, phase II enzymes and uptake, and efflux transporters were integrated. To represent the interaction potential, the in vitro metabolic metric (IVMM) was generated by combining the fraction of substrate metabolised by each hepatic enzyme of interest with the corresponding in vitro fold increase in enzyme activity (E) value for the inducer. RESULTS: Two independent variables were deemed significant and included in the algorithm: IVMM and fraction unbound in plasma. The observed and predicted magnitudes of the DDIs were categorised accordingly: no induction, mild, moderate, and strong induction. DDIs were assumed to be well classified if the predictions were in the same category as the observations, or if the ratio between these two was < 1.5-fold. This algorithm correctly classified 70.5% of the DDIs. CONCLUSION: This research presents a rapid screening tool to identify the magnitude of potential DDIs utilising in vitro data which can be highly advantageous in early drug development.

Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.

BACKGROUND: Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents. AIM: To explore factors associated with OAC prescription. DESIGN AND SETTING: Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18. METHOD: Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank. RESULTS: Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription. CONCLUSION: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

BACKGROUND: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. METHODS: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. RESULTS: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. CONCLUSION: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

Managing patients with comorbidities: future models of care.

One in four adults in the UK have two or more medical conditions. One in three adults admitted to hospital in the UK have five or more conditions. People with multimorbidity have poorer functional status, quality of life and health outcomes, and are higher users of ambulatory and inpatient care than those without multimorbidity. The entire healthcare system needs to change so that it can provide a better service for patients with multimorbidity. The system of healthcare professional education needs to change also. Clinical decision support has a clear role in the management of patients with multimorbidity. But, until now, clinical decision support tools have offered no support when dealing with patients with comorbidities; they have covered single conditions only. In light of this, BMJ Best Practice recently launched the Comorbidities Manager. This enables healthcare professionals to add a patient's comorbidities to an existing management plan and get a tailored plan instantly. This article outlines the importance of taking into account comorbidities when managing patients and the role that the BMJ Comorbidities Manager can play in this regard.

Exercise and nutritional interventions on sarcopenia and frailty in heart failure: a narrative review of systematic reviews and meta-analyses.

The purpose of this review is to describe the present evidence for exercise and nutritional interventions as potential contributors in the treatment of sarcopenia and frailty (i.e. muscle mass and physical function decline) and the risk of cardiorenal metabolic comorbidity in people with heart failure (HF). Evidence primarily from cross-sectional studies suggests that the prevalence of sarcopenia in people with HF is 37% for men and 33% for women, which contributes to cardiac cachexia, frailty, lower quality of life, and increased mortality rate. We explored the impact of resistance and aerobic exercise, and nutrition on measures of sarcopenia and frailty, and quality of life following the assessment of 35 systematic reviews and meta-analyses. The majority of clinical trials have focused on resistance, aerobic, and concurrent exercise to counteract the progressive loss of muscle mass and strength in people with HF, while promising effects have also been shown via utilization of vitamin D and iron supplementation by reducing tumour necrosis factor-alpha (TNF-a), c-reactive protein (CRP), and interleukin-6 (IL-6) levels. Experimental studies combining the concomitant effect of exercise and nutrition on measures of sarcopenia and frailty in people with HF are scarce. There is a pressing need for further research and well-designed clinical trials incorporating the anabolic and anti-catabolic effects of concurrent exercise and nutrition strategies in people with HF.

The Impact of Frailty and Comorbidities on Heart Failure Outcomes.

Frailty is a multisystemic process leading to reduction of physiological reserve and a reduction in physical activity. Heart failure (HF) is recognised as a global cause of morbidity and mortality, increasing in prevalence over recent decades. Because of shared phenotypes and comorbidities, there is significant overlap and a bidirectional relationship, with frail patients being at increased risk of developing HF and vice versa. Despite this, frailty is not routinely assessed in patients with HF. Identification of these patients to direct multidisciplinary care is key, and the development of a frailty assessment tool validated in a large HF population is also an unmet need that would be of considerable benefit in directing multidisciplinary-team management. Non-pharmacological treatment should be included, as exercise and physical rehabilitation programmes offer dual benefit in frail HF patients, by treating both conditions simultaneously. The evidence for nutritional supplementation is mixed, but there is evidence that a personalised approach to nutritional support in frail HF patients can improve outcomes.