Changes in the severity and lethality of age-related health deficit accumulation in the USA between 1999 and 2018: a population-based cohort study

BACKGROUND: With an ageing population, the number of people with frailty is increasing. Despite this trend, the extent to which the severity and lethality of frailty have changed over time is not well understood. We aimed to investigate how frailty severity and lethality have changed over an 18-year period in the USA. METHODS: In this population-based observational study, we used data from the National Health and Nutrition Examination Survey (NHANES) to identify community-dwelling individuals (aged ≥20 years) in the USA between 1999 and 2018. We analysed data from a series of ten 2-year, nationally representative, cross-sectional, prospective studies (from 1999–2000 to 2017–18) from the NHANES. Frailty was measured by use of the deficit accumulation approach (ie, a 46-item frailty index). The proportion of individuals categorised as non-frail, or living with very mild frailty, mild frailty, moderate frailty, and severe frailty were compared across cohorts. Random-effects models were used to examine the association between frailty index score and sex, age, and cohort. Mortality status as of Dec 31, 2015, was ascertained by use of National Death Index data, and 5-year mortality was available in the first six cohorts (1999–2010). Cox regression models and Kaplan-Meier curves were used to estimate the association between frailty index scores and mortality. FINDINGS: In total, 49 004 individuals were included in our study. Associations were mainly non-linear (quadratic), with frailty increasing at a faster rate in more recent cohorts. Between 1999 and 2018, the proportion of non-frail individuals decreased by 10·4% (from 2747 [63·8%; 95% CI 61·9–65·6] of 4307 to 2884 [53·4%; 51·3–55·5] of 5399), whereas the proportion of individuals with very mild frailty increased by 2·4% (from 987 [22·9%; 21·3–24·6] to 1365 [25·3%; 23·5–27·2]), by 2·7% (from 370 [8·6%; 7·7–9·6] to 609 [11·3%; 10·1–12·5]) in those with mild frailty, by 3·1% (from 140 [3·3%; 2·7–3·9] to 347 [6·4%; 5·6–7·4]) in those with moderate frailty, and by 2·1% (from 63 [1·5%; 1·1–1·9] to 195 [3·6%; 3·0–4·3]) in those with severe frailty. Being a woman, older, and from a more recent cohort were associated with higher frailty index scores (all p<0·0001). In more recent cohorts, mean frailty index scores increased more quickly with age (p<0·0001), and sex differences in mean frailty index scores decreased (p<0·0001). In men of all ages and in women aged 35 years or older, mean frailty index scores were higher in more recent cohorts, with larger increases in frailty in older age groups. In 28 692 individuals from the first six cohorts (1999–2000 to 2009–10) with linked mortality data, frailty index scores were significantly associated with mortality (hazard ratio 1·053 [95% CI 1·050–1·057] per 0·01 increase in frailty index score). The absence of an interaction between cohort and frailty index score (p=0·58) suggested that the association between frailty and mortality was similar for all cohorts. INTERPRETATION: Increasing frailty levels in more recent cohorts of middle-aged and older adults combined with stable frailty lethality between 1999 and 2018, suggest a challenge to healthy longevity, with the proportion of individuals with a high degree of frailty continuing to increase. FUNDING: Supported in part by the Canadian Institutes of Health Research

Piloting data linkage in a prospective cohort study of a GP referral scheme to avoid unnecessary emergency department conveyance

BACKGROUND: UK Ambulance services are under pressure to safely stream appropriate patients away from the Emergency Department (ED). Even so, there has been little evaluation of patient outcomes. We investigated differences between patients who are conveyed directly to ED after calling 999 and those referred by an ambulance crew to a novel GP referral scheme. METHODS: This was a prospective study comparing patients from two cohorts, one conveyed directly to the ED (n = 4219) and the other referred to a GP by the on-scene paramedic (n = 321). To compare differences in patient outcomes, we include follow-up data of a smaller subset of each cohort (up to n = 150 in each) including hospital admission, history of long-term illness, previous ED attendance, length of stay, hospital investigations, internal transfers, 30-day re-admission and 10-month mortality. RESULTS: Older individuals, females, and those with minor incidents were more likely to be referred to a GP than conveyed directly to ED. Of those patients referred to the GP, only 22.4% presented at ED within 30 days. These patients were more likely to be admitted then than were those initially conveyed directly to ED (59% vs 31%). Those conveyed to ED had a higher risk of death compared to those who were referred to the GP (HR: 2.59; 95% CI 1.14–5.89), however when analyses were restricted to those who presented at ED within 30 days, there was no difference in mortality risk (HR: 1.45; 95% CI 0.58–3.65). CONCLUSIONS: Despite limited data and a small sample size, there were differences between patients conveyed directly to ED and those who were referred into GP care. Initial evidence suggests that referring individuals to a GP may provide an appropriate and safe alternative path of care. This pilot study demonstrated a need for larger scale, methodologically rigorous study to demonstrate the benefits of alternative conveyance schemes and recommend changes to the current system of urgent and emergency care

Associations between a laboratory frailty index and adverse health outcomes across age and sex

Objective: Early frailty may be captured by a frailty index (FI) based entirely on vital signs and laboratory tests. Our aim was to examine associations between a laboratory-based FI (FI-Lab) and adverse health outcomes, and investigate how this changed with age. Methods: Up to 8988 individuals aged 20+ years from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey cohorts were included. Characteristics of the FI-Lab were compared to those of a self-reported clinical FI. Associations between each FI and health care use, self-reported health, and disability were examined in the full sample and across age groups. Results: Laboratory-based FI scores increased with age but did not demonstrate expected sex differences. Women aged 20-39 years had higher FI scores than men; this pattern reversed after age 60 years. FI-Lab scores were associated with poor self-reported health (odds ratio[95% confidence interval]: 1.46[1.39-1.54]), high health care use (1.35[1.29-1.42]), and high disability (1.41[1.32-1.50]), even among those aged 20-39 years. Conclusion: Higher FI-Lab scores were associated with poor health outcomes at all ages. Associations in the youngest group support the notion that deficit accumulation occurs across the lifespan. FI-Lab scores could be utilized as an early screening tool to identify deficit accumulation at the cellular and molecular level before they become clinically visible

Incomplete functional recovery after delirium in elderly people: a prospective cohort study

BACKGROUND: Delirium often has a poor outcome, but why some people have incomplete recovery is not well understood. Our objective was to identify factors associated with short-term (by discharge) and long-term (by 6 month) incomplete recovery of function following delirium. METHODS: In a prospective cohort study of elderly patients with delirium seen by geriatric medicine services, function was assessed at baseline, at hospital discharge and at six months. RESULTS: Of 77 patients, vital and functional status at 6 months was known for 71, of whom 21 (30%) had died. Incomplete functional recovery, defined as ≥10 point decline in the Barthel Index, compared to pre-morbid status, was present in 27 (54%) of the 50 survivors. Factors associated with death or loss of function at hospital discharge were frailty, absence of agitation (hypoactive delirium), a cardiac cause and poor recognition of delirium by the treating service. Frailty, causes other than medications, and poor recognition of delirium by the treating service were associated with death or poor functional recovery at 6 months. CONCLUSION: Pre-existing frailty, cardiac cause of delirium, and poor early recognition by treating physicians are associated with worse outcomes. Many physicians view the adverse outcomes of delirium as intractable. While in some measure this might be true, more skilled care is a potential remedy within their grasp

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt

Reduced Health-Related Quality of Life in Elders with Frailty: A Cross-Sectional Study of Community-Dwelling Elders in Taiwan

PURPOSE: Exploring the domains and degrees of health-related quality of life (HRQOL) that are affected by the frailty of elders will help clinicians understand the impact of frailty. This association has not been investigated in community-dwelling elders. Therefore, we examined the domains and degree of HRQOL of elders with frailty in the community in Taiwan. METHODS: A total of 933 subjects aged 65 years and over were recruited in 2009 from a metropolitan city in Taiwan. Using an adoption of the Fried criteria, frailty was defined by five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity level. HRQOL was assessed by the short form 36 (SF-36). The multiple linear regression model was used to test the independent effects of frailty on HRQOL. RESULTS: After multivariate adjustment, elders without frailty reported significantly better health than did the pre-frail and frail elders on all scales, and the pre-frail elders reported better health than did the frail elders for all scales except the scales of role limitation due to physical and emotional problems and the Mental Component Summary (MCS). The significantly negative differences between frail and robust elders ranged from 3.58 points for the MCS to 22.92 points for the physical functioning scale. The magnitude of the effects of frail components was largest for poor endurance and energy, and next was for slowness. The percentages of the variations of these 10 scales explained by all factors in the models ranged from 11.1% (scale of role limitation due to emotional problems) to 49.1% (scale of bodily pain). CONCLUSIONS: Our study demonstrates that the disabilities in physical health inherent in frailty are linked to a reduction in HRQOL. Such an association between clinical measures and a generic measure of the HRQOL may offer clinicians new information to understand frailty and to conceptualize it within the broader context of disability

Acromioclavicular joint reconstruction with coracoacromial ligament transfer using the docking technique

<p>Abstract</p> <p>Background</p> <p>Symptomatic Acromioclavicular (AC) dislocations have historically been surgically treated with Coracoclavicular (CC) ligament reconstruction with transfer of the Coracoacromial (CA) ligament. Tensioning the CA ligament is the key to success.</p> <p>Methods</p> <p>Seventeen patients with chronic, symptomatic Type III AC joint or acute Type IV and V injuries were treated surgically. The distal clavicle was resected and stabilized with CC ligament reconstruction using the CA ligament. The CA ligament was passed into the medullary canal and tensioned, using a modified 'docking' technique. Average follow-up was 29 months (range 12–57).</p> <p>Results</p> <p>Postoperative ASES and pain significantly improved in all patients (p = 0.001). Radiographically, 16 (94%) maintained reduction, and only 1 (6%) had a recurrent dislocation when he returned to karate 3 months postoperatively. His ultimate clinical outcome was excellent.</p> <p>Conclusion</p> <p>The docking procedure allows for tensioning of the transferred CA ligament and healing of the ligament in an intramedullary bone tunnel. Excellent clinical results were achieved, decreasing the risk of recurrent distal clavicle instability.</p

Frailty Intervention Trial (FIT)

<p>Abstract</p> <p>Background</p> <p>Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity). Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty.</p> <p>We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people.</p> <p>Methods and Design</p> <p>A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period.</p> <p>Discussion</p> <p>This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation. The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trails Registry: ACTRN12608000250336.</p

Inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection: a prospective cohort study and immunological network analysis

Background HIV-1 mediated dysregulation of the immune response to tuberculosis and its effect on the response to antitubercular therapy (ATT) is incompletely understood. We aimed to analyse the inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection undergoing ATT, with specific focus on the effect of ART and HIV-1 viraemia in those co-infected with HIV-1. Methods In this prospective cohort study and immunological network analysis, a panel of 38 inflammatory markers were measured in the plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B clinic, Cape Town, South Africa. We recruited patients with sputum Xpert MTB/RIF-positive rifampicin-susceptible pulmonary tuberculosis. Patients were excluded from the primary discovery cohort if they were younger than 18 years, unable to commence ATT for any reason, pregnant, had unknown HIV-1 status, were unable to consent to study participation, were unable to provide baseline sputum samples, had more than three doses of ATT, or were being re-treated for tuberculosis within 6 months of their previous ATT regimen. Plasma samples were collected at baseline (1–5 days after commencing ATT), week 8, and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. In addition to the discovery cohort, a validation cohort of patients with HIV-1 admitted to hospital with CD4 counts less than 350 cells per μL and a high clinical suspicion of new tuberculosis were recruited. Findings Between March 1, 2013, and July 31, 2014, we assessed a cohort of 129 participants (55 [43%] female and 74 [57%] male, median age 35·1 years [IQR 30·1–43·7]) and 76 were co-infected with HIV-1. HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and having a strong effect on correlation profiles observed in the HIV-1 co-infected group. Interleukin (IL)-17A emerged as a key correlate of HIV-1-induced inflammation during HIV–tuberculosis co-infection. Interpretation Our findings show the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in patients with tuberculosis. Through network analysis we identified IL-17A as an important node in HIV–tuberculosis co-infection, thus implicating this cytokine's capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are required to identify specific IL-17A-related inflammatory pathways mediating immunopathology in HIV–tuberculosis co-infection, which could illuminate targets for future host-directed therapies. Funding National Institutes of Health, The Wellcome Trust, UK Research and Innovation, Cancer Research UK, European and Developing Countries Clinical Trials Partnership, and South African Medical Research Council