Homeostatic Reserve Research Articles

Factors Associated With Frailty Among Older Adults Attending a Rural Public Primary Care Clinic in Malaysia

Introduction: Frailty is a condition occurring in older age with a reduction in homeostatic reserve and inability to react against external stressors. This resulted in falls, disability, loss of independence and mortality. At present, there are limited studies on frailty in the rural settings in Malaysia. We aimed to determine the proportion of frailty and the factors associated with frailty among older adults attending a rural clinic in Selangor. Methods: A cross-sectional study involving older adults aged >60 years who attended a rural public healthcare clinic were recruited from February-April 2018 using a systematic random sampling method. Face-to-face interview using structured pretested questionnaires and physical assessment was conducted. Data collected included socio-demography, frailty status, functional status, cognitive function, self-reported chronic diseases and polypharmacy. All analyses were done using SPSS software version 22.0. Results: The response rate was 93% with 250 participants. A total of 29 (11.6%) participants were frail and 75 (30%) were pre-frail. The factors associated with pre-frail and frail among older adults were the presence of two chronic diseases or more (aOR=4.89; 95%CI=1.29, 18.51; p=0.019), presence of polypharmacy (aOR=1.97; 95%CI=1.05, 3.72; p=0.035), abnormal walking speed based on Time Up and Go test (aOR=12.80; 95%CI=4.57, 35.86; p<0.001), and dependent IADLs based on Lawton’s IADLs (aOR= 3.06; 95%CI=1.28, 7.33; p=0.012). Conclusion: Older adults attending the rural primary clinic with risk factors such as multiple chronic diseases and polypharmacy should be screened for frailty as the condition is potentially reversible if interventions are started early.

The frail patient undergoing cardiac surgery: lessons learned and future perspectives.

Frailty is a geriatric condition characterized by the reduction of the individual's homeostatic reserves. It determines an increased vulnerability to endogenous and exogenous stressors and can lead to poor outcomes. It is an emerging concept in perioperative medicine, since an increasing number of patients undergoing surgical interventions are older and the traditional models of care seem to be inadequate to satisfy these patients' emerging clinical needs. Nowadays, the progressive technical and clinical improvements allow to offer cardiac operations to an older, sicker and frail population. For these reasons, a multidisciplinary team involving cardiac surgeons, clinical cardiologists, anesthesiologists, and geriatricians, is often needed to assess, select and provide tailored care to these high-risk frail patients to optimize clinical outcomes. There is unanimous agreement that frailty assessment may capture the individual's biological decline and the heterogeneity in risk profile for poor health-related outcomes among people of the same age. However, since commonly used preoperative scores for cardiac surgery fail to capture frailty, a specific preoperative assessment with dedicated tools is warranted to correctly recognize, measure and quantify frailty in these patients. On the contrary, pre-operative and post-operative interventions can reduce the risk of complications and support patient recovery promoting surgical resilience. Minimally invasive cardiac procedures aim to reduce surgical trauma and may be associated with better clinical outcome in this specific sub-group of high-risk patients. Among postoperative adverse events, the occurrence of delirium represents a risk factor for several unfavorable outcomes including mortality and subsequent cognitive decline. Its presence should be carefully recognized, triggering an adequate, evidence based, treatment. There is evidence, from several cross-section and longitudinal studies, that frailty and delirium may frequently overlap, with frailty serving both as a predisposing factor and as an outcome of delirium and delirium being a marker of a latent condition of frailty. In conclusion, frail patients are at increased risk to experience poor outcome after cardiac surgery. A multidisciplinary approach aimed to recognize more vulnerable individuals, optimize pre-operative conditions, reduce surgical invasivity and improve post-operative recovery is required to obtain optimal long-term outcome.

Neurosurgical perioperative management of frail elderly patients.

With the rapid increase in global aging, the prevalence of frailty is increasing and frailty has emerged as an emerging public health burden. Frail elderly patients suffer from reduced homeostatic reserve capacity, which is associated with a disproportionate decline in physical status after exposure to stress and an increased risk of adverse events. Frailty is closely associated with changes in the volume of the white and gray matter of the brain. Sarcopenia has been suggested to be an important component of frailty, and reductions in muscle strength and muscle mass lead to reductions in physical function and independence, which are critical factors contributing to poor prognosis. Approximately 10-32% of patients undergoing neurological surgery are frail, and the risk of frailty increases with age, which is significantly associated with the occurrence of adverse postoperative events (major complications, total duration of hospitalization, and need for discharge to a nursing facility). The postoperative mortality rate in severely frail patients is 9-11 times higher than that in non-frail individuals. Therefore, due attention must be paid to neurosurgical frailty and muscle assessment in elderly patients. Specialized interventions in the perioperative period of neurosurgery in frail elderly patients may improve their postoperative prognosis.

The prevalence and importance of frailty in cardiac resynchronization therapy patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Nemzeti Kardiovaszkuláris Laboratórium RRF-2.3.1-21-2022-00003. Background Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. Aims We assessed the frequency of, and outcomes related to frailty in patients with heart failure and reduced ejection fraction who previously underwent cardiac resynchronization therapy (CRT) implantation. Methods We used a cumulative deficits approach to construct a 30-item frailty index (FI) and applied it to identify frail patients enrolled in our CRT registry. The 30 items were derived from medical history, other patient characteristics and laboratory results, covering a range of body systems. In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Our primary endpoint was all-cause mortality. Results Among 1004 included patients, 75 (7%) were considered Non-frail, while 271 (27%) and 658 (66%) participants were categorized as Frail in groups 1- and 2. Patients in Frail group 2 were older, had a less favorable renal function, and generally had more comorbidities (i.e. atrial fibrillation, hypertension, ischemic cardiovascular disease) than patients categorized in the Non-frail or Frail group 1. During the median follow-up time of 4.4 (2.3-6.9) years, 17 (22%) patients in the Non-frail group, 103 (38%) in Frail group 1, and 479 (73%) in the Frail group 2 reached the primary endpoint. Non-frail patient group showed the most beneficial survival with a 70% (HR 0.31; 95% CI: 0.23-0.41; p<0.001) lower all-cause mortality risk compared to Frail group 2. Adjusting for relevant covariates, NYHA class, creatinine, and TAPSE were identified as independent predictors for all-cause mortality. Conclusion Based on our results, CRT candidates are exceedingly vulnerable with a high prevalence of frailty. The calculated frailty index was associated with the primary outcome of death from any cause. FI proved to be prevalent in individual risk stratification and can predict the outcome.

Intergenerational Perioperative Neurocognitive Disorder.

Accelerated neurocognitive decline after general anesthesia/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem that may affect millions of patients each year. Advanced age, with its increasing prevalence of heightened stress, inflammation, and neurodegenerative alterations, is a consistent contributing factor to the development of PND. Although a strong homeostatic reserve in young adults makes them more resilient to PND, animal data suggest that young adults with pathophysiological conditions characterized by excessive stress and inflammation may be vulnerable to PND, and this altered phenotype may be passed to future offspring (intergenerational PND). The purpose of this narrative review of data in the literature and the authors' own experimental findings in rodents is to draw attention to the possibility of intergenerational PND, a new phenomenon which, if confirmed in humans, may unravel a big new population that may be affected by parental PND. In particular, we discuss the roles of stress, inflammation, and epigenetic alterations in the development of PND. We also discuss experimental findings that demonstrate the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane that interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring who have neither trauma nor anesthetic exposure (i.e., an animal model of intergenerational PND).

Prediction of Risk of Frailty Among Institutionalized Older Adults in India.

Frailty is a state of age-related physiological vulnerability resulting from impaired homeostatic reserve and a reduced capacity of the individual to withstand stress and an independent predictor of deleterious health outcomes among the aged. Early identification of people who are at risk for frailty is vital in preventing and minimizing its socio-economic consequences in low-resource countries like India. However, risk factors for frailty among Indian institutionalized older adults have been seldom explored. The objective of this study is to develop a prediction model for the risk of frailty among institutionalized older adults. This study adopted a case-control design, wherein institutionalized adults were categorized into frail and non-frail, using Fried's criteria. Individuals above 55 years of age who could follow instructions without severe motor and cognitive impairment and terminal illness were recruited from nine conveniently selected institutions. Socio-demographic, lifestyle, behavioral, and physical performance factors were evaluated by including hundred participants. Among the fourteen independent variables, age, cognition, income, functional mobility, polypharmacy and presence of more than 3 comorbidities were significant in univariate analysis. But adjusted odds ratio showed a statistical significance for low educational status, low income, poor functional mobility, and presence of more than 3 co-morbidities only, hence they were used for developing the prediction model. Low education status, low income, poor functional mobility, and presence of more than 3 comorbidities were found to have a significant association with the risk of frailty. A model has been developed to predict the risk and early identification of frailty among institutionalized older adults.

The concept and practical management of frailty in neurology

Frailty is a clinical situation of decreased homeostatic reserve that, after a minor trigger (acute illness, fall, taking a drug...) increases the risk of an adverse event such as hospital admission, institutionalization, functional and/or cognitive decline, death, etc. Frailty can be understood as physical frailty, Fried's phenotype, a true geriatric syndrome that can be reversible by avoiding its progression to more advanced stages of irreversibility and dependence, and Rockwood's frailty due to accumulation of deficits, as a continuum of health or classification typology of the elderly along the frailty spectrum (healthy, robust, vulnerable, mild-moderate-severe and extreme frailty or end of life). The diagnosis of physical frailty is part of the comprehensive geriatric assessment, recommending the use of a performance test such as gait speed (<0,8m/s), Timed Up and Go (>12 s) or Short Physical Performance Battery (<10). Physical frailty is reversible by a multidisciplinary management based on three fundamental pillars: multicomponent physical exercise and resistance training, adequate protein and micronutrient intake (leucine, vitamin D, etc.) and appropriate pharmacological prescription, management of comorbidity and geriatric syndromes. Frailty is a risk factor for neurological disease progression and increased risk of adverse events in neurodegenerative diseases such as mild cognitive impairment, dementia, Parkinson's disease and cerebrovascular disease. Frailty based on the Clinical Frailty Scale or VIG-Frail shows patient typologies in relation to a greater or lesser state of fragility, being a basic prognostic tool of great utility in making diagnostic and therapeutic management decisions. It opens up a new opportunity for improvement in the management of neurological disease in the diagnosis and treatment of frailty.

The impact of frailty index on long-term outcome in CRT patients

Abstract Background Frailty is a complex clinical syndrome associated with ageing and comorbidities resulting from multiple organ impairment by losing homeostatic reserves and increased vulnerability to physiological decompensation. Frailty can be measured by quantifying the “vulnerability status” by the range of comorbidities. Purpose We assessed the long-term all-cause mortality based on Frailty Index (FI) among patients who underwent Cardiac Resynchronization Therapy (CRT) implantation. Methods We calculated patients' FI individually using 30 clinical parameters from our retrospective single centre large-scale registry. The applied clinical features incorporated patients' medical history, anthropometric-, laboratory and echocardiographic parameters. Based on previous studies, patients with FI ≤0.210 were classified as non-frail, and patients above that value were considered frail. Frail patients were divided into two different subgroups (F1; F2) by a FI increment of 0.100 based on the Rockwood method. Primary endpoint was all-cause mortality, log-rank and Cox multivariate analysis were performed. Results Among 1010 included patients, 58 (6%) were considered as Non-frail, while 245 (24%) and 707 (70%) participants were categorized to F1- and F2 groups. Patients in F2 group were older [non-frail 62 years (IQR 57–68) vs. F1 66 years (IQR 57–73) vs. F2 70 years (IQR 63–76); p&amp;lt;0.001], had worse laboratory parameters as higher creatinine, uric acid, lower sodium or hemoglobin levels (p&amp;lt;0.001) and more comorbidities than patients of Non-frail or F1 groups. During the median follow-up time of 4.4 (2.3–6.9) years, 17 (29%) patients in the Non-frail group, 103 (42%) in Frail group 1 and 479 (68%) in the Frail group 2 reached the primary endpoint. Non-frail patients showed the best outcome, and patients in the Frail group 1 demonstrated a 46% (HR 0.46, 95% CI 0.39–0.55; p&amp;lt;0.001) lower all-cause mortality risk compared to Frail group 2. In the total cohort, mortality predictors were also assessed, NYHA functional class, serum sodium, creatinine and TAPSE were identified as independent predictors of all-cause mortality. Conclusion By calculating individual frailty index among CRT patients, distinct groups could be identified, of which mortality differed significantly. Those with the highest Frailty index demonstrated the worse outcome compared to lower index or non-frail patients. Frailty index can help selecting the most vulnerable patients, requiring a strict follow-up. Funding Acknowledgement Type of funding sources: None.

Immune dysfunction in millitary personnel participating in special tasks and the possibility of medical and psychological rehabilitation

The article considers immune dysfunction in military personnel participating in special operations and the possibilities of their medical and psychological rehabilitation. The state of the immune status of 73 servicemen (average age 37.6 4.1 years) who participated in special operations in areas with a difficult operational situation and underwent a 20-day standard course of medical and psychological rehabilitation in the sanatoriums of the sanatorium complexes North Caucasian, Sochi, and Crimean was monitored. Immune status was assessed before and after participation in special operations and after a course of medical and psychological rehabilitation. Immune dysfunction due to quantitative and functional changes in the immune status was established. Soldiers participating in special operations registered a decrease in the synthesis and differentiation of T-lymphocytes, inhibition of the functionality of cytotoxic lymphocytes, reduced cytolytic potential of natural killer cells, impaired antigen-presenting function of monocytes, and a significant decrease in the number of B lymphocytes with preserved antibody-producing function. The rehabilitation course for military personnel participating in special operations led to the normalization of the analyzed parameters, except for the functional activity of natural killer cells and monocytes. Given the lack of full recovery of homeostatic reserves in the immune system, a more in-depth study of the problem and development of a personalized approach to rehabilitation of the military participants with the assessment of immunological markers are necessary.

STRENGTHENING OF PHYSICAL PERFORMANCE IN FRAIL ELDERLY WOMEN WITH METABOLIC SINDROME

Objective: This study assessed homeostatic reserves which frailty includes through the differences in physical performances by elderly women affected by Metabolic Syndrome. Design and method: We examined 32 women (mean age 68+ 3) with Metabolic Syndrome.Metabolic Syndrome was assessed through the NCEP standards: 1) obesity (waist&gt;cm 88 for women and&gt; 102 cm for men); 2) high values of triglyceride (&gt;150 mg/dl); 3) low values of HDL cholesterol (&gt;40 mg/dl for men and 50 mg/dl for women);4) high levels of blood pressure (&gt; 130/85 mmHg) or antihypertensive treatment; 5) high glycemia at awakening (110–126 mg/dl). The design of the study included: 1) blood tests; 2) clinical measurement of blood pressure.Blood Pressure was under control when&lt; 140/90 mmHg and &gt; 130/80 mmHg in patients affected by diabetes mellitus.The Short Physical Performance Battery (SPPB) combines a balance test following 3 different positions on increasing difficulty, a 4-metre walking path and a repeated stand-up exercise from a chair.Self-sufficient elderly women with reduced physical performance and with a reported SPPB score comprised between 5 and 9 can be considered frail and at high risk of disability. Results: Among all subjects 16 had a &lt; 9 SPPB score (group A); while 18 had a &gt; 9 score (group B). We did not detect considerable differences in the 2 groups considering age, waist length, glycemia, cholesterol, triglyceride, while we detected an uncontrolled hypertension (SBP 154 + 3 and DBP 90 + 4 mmHg, p&lt; 0.005) in group A. A substantial connection between reduced physical performance (SPPB &lt; 9) and uncontrolled hypertension in group A (p &lt; 0.01) was noted. The latter was administered a 6 month program of home adapted workout supervised by an occupational therapist every 2 months. Conclusions: In elderly women affected by Metabolic Syndrome, the study assesses a relationship between uncontrolled hypertension and a reduced physical performance. Evaluation through SPPB is able to assess specific features in elderly patients’ health beyond the clinical evaluation and the specific markers for disease gravity, therefore indicating the reduced homeostatic reserves included in frailty. A combination of pharmacological therapy with occupational therapy is able to empower physical performance in frail elderly patients.

Measurement of Sarcopenia in Head and Neck Cancer Patients and Its Association With Frailty.

In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients.

Reframing Palliative Care: An East-West Integrative Palliative Care Model.

Convergence of principles of palliative care and integrative medicine has led to the introduction of the new practice of integrative palliative care in which integrative therapies (including mind-body modalities, traditional Chinese medicine, Ayurveda, and dietary supplements) are used to provide symptom management for patients who are dying or experiencing the sequelae of serious illness and its treatment. We propose an East-West Integrative palliative care model using non-drug therapies, such as acupuncture, diet, exercise, and stress management that shift the paradigm from suppressing the symptoms of illness to addressing both the root cause of the symptoms and the imbalance and declining homeostatic reserve that perpetuate these symptoms. This whole-person model expands the reach of palliative care, prolonging a better quality of life and allowing the patient to maintain as many activities as possible by preventing symptoms and improving function. Through this approach we reframe the dialogue such that patients are “living better” rather than “dying better” when faced with serious illness or death. In this article, we provide an overview of the principles of palliative care, integrative medicine, and the novel area of integrative palliative care, and propose an East-West integrative palliative care model that incorporates and broadens the scope of these existing approaches.

Age-related compensation: Neuromusculoskeletal capacity, reserve & movement objectives

The prevention, mitigation and treatment of movement impairments, ideally, requires early diagnosis or identification. As the human movement system has physiological and functional redundancy, movement limitations do not promptly arise at the onset of physical decline. A such, prediction of movement limitations is complex: it is unclear how much decline can be tolerated before movement limitations start. Currently, the term ‘homeostatic reserve’ or ‘physiological reserve’ is used to refer to the redundancy of the human biological system, but these terms do not describe the redundancy in the muscle architecture of the human body. The result of functional redundancy is compensation. Although compensation is an early predictor of movement limitations, clear definitions are lacking and the topic is underexposed in literature. The aim of this article is to provide a definition of compensation and emphasize its importance. Compensation is defined as an alteration in the movement trajectory and/or altering muscle recruitment to complete a movement task. Compensation for capacity is the result of a lack in neuromusculoskeletal reserve, where reserve is defined as the difference between the capacity (physiological abilities of the neuromusculoskeletal system) and the task demand. Compensation for movement objectives is a result of a shift in weighting of movement objectives, reflecting changing priorities. Studying compensation in biomechanics requires altered protocols in experimental set-ups, musculoskeletal models that are not reliant on prescribed movement, and inclusion of alternative movement objectives in optimal control theory.

106 Frailty Assessment in the Burn Population: A Single Center Retrospective Review

Abstract Introduction Burn morbidity and mortality increases with advancing age. Frailty is characterized by reduced homeostatic reserves and is associated with an increased biological age compared to chronological age. Our primary aim was to determine whether frailty as assessed on admission would be predictive of outcomes in the burn population. Methods We conducted a single institution 7-month retrospective chart review of all admitted acute burn patients ages 45 and older. Patient and injury characteristics were collected and compared using standard statistical analysis. Frailty scores were assessed upon admission using the FRAIL Scale. Results Eighty-five patients met inclusion criteria and were able to complete the FRAIL assessment. Patient and injury characteristics are listed in Table 1. Mean burn size was 6.7%TBSA (95%CI 4.9–8.4%). 34 patients (40%) were classified as robust (FRAIL score 0), 26(30.6%) as pre-frail (FRAIL score 1-Patients in the pre-frail/frail cohort received more palliative care consultations (p=.096) and had a longer length of stay (3.3d vs 7.55d p = .002), while prefrail patients had a similar LOS to frail patients (7.46 vs 7.64d p =.938). Patients in the pre-frail/frail cohort were also more likely to be discharged to a higher level of care than they were admitted from(p=.032) with prefrail patients experience an escalation in level of care more frequently than frail patients. The distribution by age by half-decade ranges is in Figure 1. By age 55–59, the majority of patients were prefrail or frail. Conclusions We demonstrated that frailty as assessed by the FRAIL score was predictive of increased length of stay and an escalation in post discharge care. In addition, patients characterized as pre-frail experience outcomes similar to frail patients and should be managed as such. Given the prevalence of frailty and prefrailty in the younger group of patients, we advocate for routine frailty screening beginning at age 55.

Frailty, MRI, and FDG-PET Measures in an Australian Memory Clinic Cohort

Given that the global population is aging, the number of age-related syndromes, such as frailty, is expected to rise in conjunction. Frailty is characterized by the loss of homeostatic reserve, rendering the individual vulnerable to poor health outcomes. Many biological mechanisms have been proposed to contribute to frailty. However, few studies have assessed the associations between frailty and brain diseases or neuroimaging biomarkers.Aims: The aims of this study were to measure the prevalence of frailty in a memory clinic and to examine associations between frailty and brain changes found on magnetic resonance imaging (MRI) and 18-F deoxyglucose (FDG) positron emission tomography (PET) in memory clinic attendees.Methods: A 54-items Frailty Index was retrospectively assessed for all clinic attendees from 2014. Frailty was defined as FI > 0.25. MR images were analyzed for stroke, cerebral small vessel disease [CSVD, including cerebral microbleeds (CMBs), cortical superficial siderosis (CSS), and white matter hyperintensity (WMH)], and neurodegenerative changes [MRI: mesial temporal atrophy (MTA), FDG-PET: regional hypometabolism], blind to clinical findings.Results: There were 209 clinic attendees in 2014, of whom 121 had MRI performed. The prevalence of frailty (using FI) in the memory clinic in 2014 was 38.3% overall (patients without MRI: 43.2%, patients with MRI 34.7%, p = 0.25). Frailty was associated with presence of deep WMH, increased severity of periventricular WMH, and presence of CSS, but not neurodegeneration markers (MTA atrophy/FDG-PET hypometabolism).Conclusion: The findings support the idea that previously reported associations between frailty and imaging evidence of CSVD in other cohorts are also relevant to the Australian clinic setting. Given that a large proportion of memory clinic attendees are frail, there may be opportunities for interventions to reduce preventable adverse health outcomes, such as falls and fractures, and reduce the prevalence and impact of frailty in this cohort.

Covid-19 Pandemic: Maximizing Future Vaccination Treatments Considering Aging and Frailty.

The COVID-19 pandemic is proving to be a multiplier of inequalities. Especially toward the elderly population. A voiceless scream that comes from geriatrics, nursing homes, hospices from all over Italy. They call it the silent massacre: from North to South, the bulletin of coronavirus positive—or already deceased—elderly people continues to grow exponentially without a chance to counter it. Population aging and chronicity are a question that needs to be addressed. Frailty is the most challenging expression of population aging, with major consequences for public health and clinical practice. It is a geriatric syndrome which consists in a state of higher vulnerability to stressors attributed to a lower homeostatic reserve due to an age-related multisystem physiological change. People over 60, and especially over 80, are particularly vulnerable to severe or fatal infection. Moreover, the age-related dysregulation of the immune system in the elderly (i.e., immunosenescence and inflammaging) results in poorer responses to vaccination. Physical frailty is an effective health indicator and it has previously shown to predict the response to the seasonal flu vaccine. These findings suggest that assessing frailty in the elderly may identify those who are less likely to respond to immunization and be at higher risk for COVID-19 and its complications. Moreover, cognitive frailty and neurocognitive disorders, mental health and reduced awareness of illness negatively impact on adherence to complex medication regimens among elderly patients. A worldwide research and development blueprint have been initiated to accelerate the development of vaccines and therapeutics for the COVID-19 outbreak. Considered the above, I suggest the importance to consider aging in thinking about future Civud-19 vaccination and treatment, focusing on the possible impact of physical and cognitive frailty.

A cohort study investigating the relationship between patient reported outcome measures and pre-operative frailty in patients with operable, non-palliative colorectal cancer

BackgroundFrailty refers to the reduction in homeostatic reserve resulting from an accumulation of physiological deficits over a lifetime. Frailty is common in older patients undergoing surgery and is an independent risk factor for post-operative mortality, morbidity and increased length of hospital stay. In frail individuals, stressors, such as surgery, can precipitate an acute deterioration in health, manifesting as delirium, falls, reduction in mobility or continence, rendering these individuals at an increased risk of adverse perioperative outcomes. However, little is known about how frailty affects the patient experience, functional ability and quality of life (QoL) after surgery. In addition, the distribution of frailty in this population is unknown.MethodsWe will conduct a multi-centre observational trial to investigate the relationship between patient reported outcome measures and preoperative frailty. We aim to recruit approximately two-hundred patients with operable, potentially curative colorectal cancer. Eligible patients will be identified at three hospital sites. QoL and functional ability (measured using EORTC QLQ-C30 and WHO-DAS 2.0 respectively) will be recorded at the pre-operative assessment clinic, and at 6 and 12 weeks postoperatively. Frailty scores including the Edmonton Frail Scale (EFS) and Rockwood clinical frailty scale (CFS) will be calculated both preoperatively, and at 12 weeks post-operatively. Secondary outcome measures including post-operative morbidity and mortality will be measured using Clavien Dindo classification and 90-day mortality.DiscussionThis observational feasibility study seeks to define the prevalence of frailty in older (> 65 years) colorectal cancer patients and understand how frailty impacts on patient reported outcome measures. This information will help to inform larger studies relating to treatment decision algorithms and promote shared decision making in this population.

Thyroid hormones and frailty in persons experiencing extreme longevity.

The aging phenotype is quite heterogeneous, being the result of the capability of each individual to successfully or unsuccessfully response to stressors. The reduction of homeostatic reserve characterizing aging is accompanied by a remodeling of the endocrine system. Frailty has been indicated as a promising way for capturing the physiological decline as well as the biological aging of the individuals. In particular, the Frailty Index (FI), based on the assumption that health deficits tend to accumulate with aging, represents a quantitative measure of extreme interest. The study aims to correlate the thyroid hormone levels with FI in a population of centenarians and their offspring to capture the effects of thyroid remodeling in extreme longevity. The study described 593 well-characterized Italian subjects, including 180 centenarians, as well as 276 centenarian's offspring and 137 age-matched controls. FT3 levels and FT3/FT4 ratio were significantly lower (p<0.001) and TSH levels higher (p<0.001) in centenarians compared to the other groups, analysing both overall subjects and excluding subjects with hormone levels out of the normal ranges. In overall centenarians, we observed a negative correlation between FI and FT3 (ρ: -0.281, p<0.001), FT3/FT4 (ρ: -0.344, p<0.001) and TSH (ρ: -0.223, p 0.003) and a positive association between FI and FT4 (ρ: 0.189, p=0.001). In centenarians with hormone levels within the normal ranges, similar negative correlations were observed between FI and FT3 (ρ: -0.201, p=0.02) and FT3/FT4 (ρ: -0.264, p=0.002). In this sub-analysis, FI positively correlated with FT4 and age (ρ: 0.167, p=0.05; ρ: 0.219, p=0.005, respectively). Conversely, no significant correlations were observed between hormone levels and FI in offspring and controls. We found an association between thyroid hormone levels and frailty in centenarians, underlying the significant role of thyroid in the aging process and longevity.

The prevalence and importance of frailty in heart failure with reduced ejection fraction-an analysis of PARADIGM-HF and ATMOSPHERE.

Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of 'health deficits' across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF). Using a cumulative deficits approach, we constructed a 42-item frailty index (FI) and applied it to identify frail patients enrolled in two HFrEF trials (PARADIGM-HF and ATMOSPHERE). In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Clinical outcomes were examined, adjusting for prognostic variables. Among 13 625 participants, mean (± standard deviation) FI was 0.250 (0.10) and 8383 patients (63%) were frail (FI >0.210). The frailest patients were older and had more symptoms and signs of heart failure. Women were frailer than men. All outcomes were worse in the frailest, with high rates of all-cause death or all-cause hospitalization: 40.7 (39.1-42.4) vs. 22.1 (21.2-23.0) per 100 person-years in the non-frail; adjusted hazard ratio 1.63 (1.53-1.75) (P < 0.001). The rate of all-cause hospitalizations, taking account of recurrences, was 61.5 (59.8-63.1) vs. 31.2 (30.3-32.2) per 100 person-years (incidence rate ratio 1.76; 1.62-1.90; P < 0.001). Frailty is highly prevalent in HFrEF and associated with greater deterioration in quality of life and higher risk of hospitalization and death. Strategies to prevent and treat frailty are needed in HFrEF.

72 Frailty Assessment in the Burn Population: A Single Center Retrospective Review

Abstract Introduction Burn morbidity and mortality increases with advancing age. Frailty is characterized by reduced homeostatic reserves and is associated with an increased biological age compared to chronological age. Our primary aim was to determine whether frailty as assessed on admission would be predictive of outcomes in the burn population. Methods We conducted a single institution 7-month retrospective chart review of all admitted acute burn patients ages 45 and older. Patient and injury characteristics were collected and compared using standard statistical analysis. Frailty scores were assessed upon admission using the FRAIL Scale. Results Eighty-five patients met inclusion criteria and were able to complete the FRAIL assessment. Patient and injury characteristics are listed in Table 1. . Mean burn size was 6.7%TBSA (95%CI 4.9–8.4%). 34 patients (40%) were classified as robust (FRAIL score 0), 26(30.6%) as pre-frail (FRAIL score 1–2) and 25(29.4) as frail (FRAIL score 3–5). When comparing the robust, pre-frail, and frail cohorts, there was no difference between potentially confounding variables including %TBSA, presence of inhalation injury, presence of full thickness burns, intubation status on admission, presence of infection on admission, mechanism of injury, or delayed presentation status. There was no difference between the robust cohort compared to the pre-frail/frail cohort in overall mortality (p=.971), Patients in the pre-frail/frail cohort received more palliative care consultations (p=.096) and had a longer length of stay (3.3d vs 7.55d p = .002), while prefrail patients had a similar LOS to frail patients (7.46 vs 7.64d p =.938). Patients in the pre-frail/frail cohort were also more likely to be discharged to a higher level of care than they were admitted from(p=.032) with prefrail patients experience an escalation in level of care more frequently than frail patients. The distribution by age by half-decade ranges is in Figure 1. By age 55–59, the majority of patients were prefrail or frail. Conclusions We demonstrated that frailty as assessed by the FRAIL score was predictive of increased length of stay and an escalation in post discharge care. In addition, patients characterized as pre-frail experience outcomes similar to frail patients and should be managed as such. Given the prevalence of frailty and prefrailty in the younger group of patients, we advocate for routine frailty screening beginning at age 55. Applicability of Research to Practice Frailty scores upon admission may allow for a more complete assessment of a patient’s functional status and can help guide discussions of expected outcomes.