Frailty in younger adults in hospital.

BACKGROUND: Even though frailty has been extensively measured in the acute care setting, relatively little is known about the frailty of younger adult inpatients. AIM: This study aimed to measure frailty in a sample of hospitalized adults aged 18 years and over and to examine how frailty in younger adult inpatients differs from middle-aged and older adult inpatients. DESIGN: Secondary analyses of prospectively collected cohort data. METHODS: Research nurses assessed 910 patients at admission to four Australian hospitals using the interRAI Acute Care instrument. Comparison of frailty index (FI) scores and domains was conducted across three age groups: younger (18-49 years), middle-aged (50-69 years) and older adults (≥70 years). Multivariable logistic regression examined risk of prolonged length of stay and unfavourable discharge destination. RESULTS: Younger adults (n = 214; 23.5%) had a mean (SD) FI of 0.19 (0.10). Approximately 27% (n = 57) of younger adults were frail (FI > 0.25). Mood and behaviour, health symptoms and syndromes, nutrition and pain were the most frequently affected domains in younger adults and 50% had ≥3 comorbidities. Frailty increased the risk of long length of stay (odds ratio (OR) = 1.77, P < 0.001) but not the risk of an unfavourable discharge (OR = 1.40, P = 0.20) in younger adults. CONCLUSIONS: This study showed that frailty is prevalent in younger patients admitted to acute care and is associated with adverse outcomes. This study was a critical first step towards establishing an understanding of frailty in younger hospitalized adults.

Quantitative assessment of the relationship between body mass index and risk of pulmonary embolism: a retrospective case-control study.

In the context of a significant increase in obesity rates, quantifying the relationship between body mass index (BMI) and risk of pulmonary embolism (PE) is an essential component of accurate clinical risk assessment. This observational study is the first to explore this association by clinician-defined cause of the PE. We demonstrate that the association between BMI and PE is driven by patients with otherwise 'unprovoked' PE where there is a strong positive correlation with odds ratios equivalent to well-recognised major risk factors such as cancer, pregnancy and surgery. We make a case for the inclusion of BMI in risk-prediction tools.

Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals-a cluster randomised controlled trial.

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Quantitative assessment of the relative effects of patient and pulmonary embolism-related factors on longer-term mortality after pulmonary embolism.

This observational study used a large audit dataset to examine the relative effects of patient-related factors and those related to the pulmonary embolism (PE) on longer-term mortality after PE. We identified that longer-term mortality is higher in provoked compared to unprovoked PE and that, in this group, obesity is relatively protective. Simplified PE severity index (sPESI), known to link to short term mortality, remains predictive in the longer-term and there is no relationship of mortality to right heart strain or extent of clot. Interestingly mortality is higher in those with negative CTPA scans than those with PE. These clinically important results should encourage careful, holistic clinical assessment of patients in these groups prior to discharge to look for treatable comorbidities.

How frail is frail? A systematic scoping review and synthesis of high impact studies.

AIMS: While the frailty index (FI) is a continuous variable, an FI score of 0.25 has construct and predictive validity to categorise community-dwelling older adults as frail or non-frail. Our study aimed to explore which FI categories (FI scores and labels) were being used in high impact studies of adults across different care settings and why these categories were being chosen by study authors. METHODS: For this systematic scoping review, Medline, Cochrane and EMBASE databases were searched for studies that measured and categorised an FI. Of 1314 articles screened, 303 met the eligibility criteria (community: N = 205; residential aged care: N = 24; acute care: N = 74). For each setting, the 10 studies with the highest field-weighted citation impact (FWCI) were identified and data, including FI scores and labels and justification provided, were extracted and analysed. RESULTS: FI scores used to distinguish frail and non-frail participants varied from 0.12 to 0.45 with 0.21 and 0.25 used most frequently. Additional categories such as mildly, moderately and severely frail were defined inconsistently. The rationale for selecting particular FI scores and labels were reported in most studies, but were not always relevant. CONCLUSIONS: High impact studies vary in the way they categorise the FI and while there is some evidence in the community-dweller literature, FI categories have not been well validated in acute and residential aged care. For the time being, in those settings, the FI should be reported as a continuous variable wherever possible. It is important to continue working towards defining frailty categories as variability in FI categorisation impacts the ability to synthesise results and to translate findings into clinical practice.

Frailty: A cost incurred by reproduction?

Evolutionary theories of senescence, such as the 'disposable soma' theory, propose that natural selection trades late survival for early fecundity. 'Frailty', a multidimensional measure of health status, may help to better define the long-term consequences of reproduction. We examined the relationship between parity and later life frailty (as measured by the Frailty Index) in a sample of 3,534 adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. We found that the most parous adults were the most frail and that the parity-frailty relationship was similar for both sexes. Whilst this study provided some evidence for a 'parity-frailty trade-off', there was little support for our hypothesis that the physiological costs of childbearing influence later life frailty. Rather, behavioural and social factors associated with rearing many children may have contributed to the development of frailty in both sexes.

Utility of Probiotics for Maintenance or Improvement of Health Status in Older People - A Scoping Review.

OBJECTIVE: To evaluate the available evidence on probiotic use in older adults from human studies. DESIGN: systematic review. METHODS: The databases Embase, CINAHL and Medline were searched in December of 2017 for studies in humans where probiotics were used to modify a health outcome in older people. The quality of studies was evaluated using the Critical Appraisal Skills Program (CASP) assessment tool and the Cochrane Risk of Bias Assessment tool. PARTICIPANTS: Subjects aged over sixty years either through specified selection criteria or where the mean participant age was greater than sixty. INTERVENTIONS: Probiotic supplements. MEASUREMENTS: Pre-specified clinically measurable health outcomes in age related conditions. RESULTS: 1210 articles were identified. After quality assessment and selection criteria were applied, 33 articles were identified to be included for review. As these studies cover a variety of applications and used customised protocols accordingly, meta-analysis was not possible and synthesis is in narrative form. CONCLUSIONS: A growing body of research has applied commercially available probiotic preparations across care settings for age related conditions including gut dysmotility, osteoporosis, common infectious diseases and cognitive impairment. Although methodologies vary, randomised controlled trials have reproduced results in these areas, and so warrant consideration of probiotics as a low risk adjuvant treatment for specific indications in the elderly.

Do sex differences in chronic disease underpin the sex-frailty paradox?

The 'male-female health-survival paradox' is a well-described clinical phenomenon. More recently, it has been conceptualized as a 'sex-frailty paradox': females may be considered to be more frail (because they have poorer health status) but also less frail (because they are less vulnerable to death) than males of the same age. Here, we review potential biological, behavioral and social mechanisms underpinning sex differences in morbidity, mortality and frailty before considering the question at the center of the sex paradox - why is it that females are able to tolerate poor health better than males? We explore, in detail, a frequently cited explanation for the sex paradox that centers on sex differences in chronic disease and conclude by presenting a new approach to this old hypothesis.

Validation of a frailty index in older cancer patients with solid tumours.

BACKGROUND: Frailty is an indicator of physiological reserve in older people. In non-cancer settings, frailty indices are reliable predictors of adverse health outcomes. The aims of this study were to 1) derive and validate a frailty index (FI) from comprehensive geriatric assessment (CGA) data obtained in the solid tumour chemotherapy setting, and 2) to explore whether the FI-CGA could predict chemotherapy decisions and survival in older cancer patients with solid tumours. METHODS: Prospective cohort study of a consecutive series sample of 175 cancer patients aged 65 and older with solid tumours. A frailty index was calculated using an accumulated deficits model, coding items from the comprehensive geriatric assessment tool administered prior to chemotherapy decision-making. The domains of physical and cognitive functioning, nutrition, mood, basic and instrumental activities of daily living, and comorbidities were incorporated as deficits into the model. RESULTS: The FI-CGA had a right-skewed distribution, with median (interquartile range) of 0.27 (0.21-0.39). The 99% limit to deficit accumulation was below the theoretical maximum of 1.0, at 0.75. The FI-CGA was significantly related (p < 0.001) to vulnerability as assessed by the Vulnerable Elders Survey-13 and to medical oncologists' assessments of fitness or vulnerability to treatment. Baseline frailty as determined by the FI-CGA was also associated with treatment decisions (Treatment Terminated, Treatment Completed, No Planned Treatment) (p < 0.001), with the No Planned Treatment group significantly frailer than the other two groups. CONCLUSION: The FI-CGA is a potentially useful adjunct to cancer clinical decision-making that could predict chemotherapy outcomes in older patients with solid tumours.

Do health assets have a protective effect for hospitalized frail older adults?

BACKGROUND: Although increasing frailty is predictive of increased mortality and length of stay for hospitalized older adults, this approach ignores health assets that individuals can utilize to recover following hospital admission. AIM: To examine whether health assets mitigate the effect of frailty on outcomes for older adults admitted to hospital. DESIGN: Patients of 1418 aged ≥ 70 years admitted to 11 hospitals in Australia were evaluated at admission using the interRAI assessment system for Acute Care, which surveys a large number of domains, including cognition, communication, mood and behaviour, activities of daily living, continence, nutrition, skin condition, falls and medical diagnosis. METHODS: The data set was interrogated for potential health assets and a multiple logistic regression adjusted for frailty index, age and gender as covariates was performed for the outcomes mortality, length of stay, re-admission and new need for residential care. RESULTS: Inpatient mortality was 3% and 4.5% of patients died within 28 days of discharge. Median length of stay was 7 days (IQR 4-11). In multivariate analysis that includes frailty, being able to walk further [OR 0.08 (0.01-0.63)], ability to leave the house [OR 0.35 (0.17-0.74)] and living alone [OR 0.28 (0.10-0.79)] were protective against mortality. The presence of a support person was associated with a decreased length of stay [OR 0.14 (0.08-0.25)]. CONCLUSION: The inclusion of health assets in predictive models can improve prognostication and highlights potential interventions to improve outcomes for hospitalized older adults.

The Utility of the Frailty Index in Clinical Decision Making.

Using clinical vignettes, this study aimed to determine if a measure of patient frailty would impact management decisions made by geriatricians regarding commonly encountered clinical situations. Electronic surveys consisting of three vignettes derived from cases commonly seen in an acute inpatient ward were distributed to geriatricians. Vignettes included patients being considered for intensive care treatment, rehabilitation, or coronary artery bypass surgery. A frailty index was generated through Comprehensive electronic Geriatric Assessment. For each vignette, respondents were asked to make a recommendation for management, based on either a brief or detailed amount of clinical information and to reconsider their decision after the addition of the frailty index. The study suggests that quantification of frailty might aid the clinical judgment now employed daily to proceed with usual care, or to modify it based on the vulnerability of the person to whom it is aimed.

Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Can granulomatosis with polyangiitis be diagnosed earlier in primary care? A case-control study.

BACKGROUND: People with granulomatosis with polyangiitis (GPA) commonly described long delays before diagnosis. AIM: To study the natural history of GPA prior to diagnosis using primary care data, and determine whether clinical features could be identified to help earlier diagnosis. DESIGN: Case-control study using the Clinical Practice Research Datalink. METHODS: We compared primary care activity and clinical features between cases and 10 matched controls. RESULTS: We identified 757 cases and matched 7546 controls. Compared to controls, cases had more GP consultations and overall healthcare activity in the 5 years prior to their diagnosis, with a marked increase in the year before diagnosis, and particularly in the last 3 months. However, consultations were mostly for symptoms that were not specifically related to GPA. In the year prior to diagnosis, the most frequent and strongly predictive clinical features of GPA were Ear Nose and Throat (ENT) symptoms [34.5% of cases, odds ratio (OR) 10.5, 95% confidence intervals (CI) 8.6-12.7], and general (constitutional) symptoms (21.5% of cases, OR 9.0, 95% CI 7.1-11.3). In the year before diagnosis a larger number of cases attended secondary care (382, 50.5%) than had records of clinical features of GPA. CONCLUSIONS: After discussing our findings, we conclude that it would be difficult to identify cases of GPA earlier in primary care. Our results support a need for heightened awareness of this condition among secondary care clinicians, especially those assessing emergency admissions, and in the clinics which were most frequently attended by cases 3-12 months prior to diagnosis.

Healthcare utilization after liver transplantation is highly variable among both centers and recipients.

The relationship between healthcare utilization before and after liver transplantation (LT), and its association with center characteristics, is incompletely understood. This was a retrospective cohort study of 34 402 adult LTs between 2002 and 2013 using Vizient inpatient claims data linked to the United Network for Organ Sharing (UNOS) database. Multivariable mixed-effects linear regression models evaluated the association between hospitalization 90 days pre-LT and the number of days alive and out of the hospital (DAOH) 1 year post-LT. Of those patients alive at LT discharge, 24.7% spent ≥30 days hospitalized during the first year. Hospitalization in the 90 days pre-LT was inversely associated with DAOH (ß = -3.4 DAOH/week hospitalized pre-LT; P = .002). Centers with >30% of their liver transplant recipients hospitalized ≥30 days in the first LT year were typically smaller volume and/or transplanting higher risk recipients (Model for End-Stage Liver Disease [MELD] score ≥35, inpatient or ventilated pre-LT). In conclusion, pre-LT hospitalization predicts 1-year post-LT hospitalization independent of MELD score at the patient-level, whereas center-specific post-LT healthcare utilization is associated with certain center behaviors and selection practices.

Perioperative assessment of older surgical patients using a frailty index-feasibility and association with adverse post-operative outcomes.

This study aimed to examine the feasibility of using a frailty index (FI) based on comprehensive geriatric assessment (CGA), to assess the level of frailty in older surgical patients preoperatively and to evaluate the association of FI-CGA with poorer postoperative outcomes. Two hundred and forty-six patients aged ≥70 years undergoing intermediate- to high-risk surgery in a tertiary hospital were recruited. Frailty was assessed using a 57-item FI-CGA form, with fit, intermediate frail, and frail patients defined as FI ≤0.25, >0.25 to 0.4, and >0.4, respectively. Adverse outcomes were ascertained at 30 days and 12 months post-surgery. Logistic regression models assessed the relationship between FI and adverse outcomes, adjusting for age, gender and acuity of surgery. The mean age of the participants was 79 years (standard deviation [SD] 6.5%), 52% were female, 91% were admitted from the community, 43% underwent acute surgery, and 19% were assessed as frail. The FI-CGA form was reported as being easy to apply, with a low patient refusal rate (2.2%). The majority of items were easy to rate, although inter-rater reliability was not tested. In relation to outcomes, greater frailty was associated with increased 12-month mortality (6.4%, 15.6%, and 23% for fit, intermediate frail, and frail patients respectively, P=0.01) and 12-month hospital readmissions (33.9%, 48.9%, and 60% respectively, P=0.004). There were no statistically significant differences between fit, intermediate frail, and frail groups in perioperative adverse events (17.4%, 23.3%, and 19.1% respectively, P=0.577) or 30-day postoperative complications (35.8%, 47.8%, and 46.8% respectively, P=0.183). Our findings suggest that it is feasible to use the FI-CGA to assess frailty preoperatively, and that using the FI-CGA may identify patients at high risk of adverse long-term outcomes.

Climate change may restrict dryland forest regeneration in the 21st century.

The persistence and geographic expansion of dryland forests in the 21st century will be influenced by how climate change supports the demographic processes associated with tree regeneration. Yet, the way that climate change may alter regeneration is unclear. We developed a quantitative framework that estimates forest regeneration potential (RP) as a function of key environmental conditions for ponderosa pine, a key dryland forest species. We integrated meteorological data and climate projections for 47 ponderosa pine forest sites across the western United States, and evaluated RP using an ecosystem water balance model. Our primary goal was to contrast conditions supporting regeneration among historical, mid-21st century and late-21st century time frames. Future climatic conditions supported 50% higher RP in 2020-2059 relative to 1910-2014. As temperatures increased more substantially in 2060-2099, seedling survival decreased, RP declined by 50%, and the frequency of years with very low RP increased from 25% to 58%. Thus, climate change may initially support higher RP and increase the likelihood of successful regeneration events, yet will ultimately reduce average RP and the frequency of years with moderate climate support of regeneration. Our results suggest that climate change alone may begin to restrict the persistence and expansion of dryland forests by limiting seedling survival in the late 21st century.

Sex differences in frailty: A systematic review and meta-analysis.

BACKGROUND: It is a well-described clinical phenomenon that females live longer than males, yet tend to experience greater levels of co-morbidity and disability. Females can therefore be considered both more frail (because they have poorer health status) and less frail (because they have a lower risk of mortality). This systematic review aimed to determine whether this ageing paradox is demonstrated when the Frailty Index (FI) is used to measure frailty. METHODS: Medline, EMBASE and CINAHL databases were searched for observational studies that measured FI and mortality in community-dwellers over 65years of age. In five-year age groups, meta-analysis determined the sex differences in mean FI (MD=mean FIfemale-mean FImale) and mortality rate. RESULTS: Of 6482 articles screened, seven articles were included. Meta-analysis of data from five studies (37,426 participants) found that MD values were positive (p<0.001; MD range=0.02-0.06) in all age groups, indicating that females had higher FI scores than males at all ages. This finding was consistent across individual studies. Heterogeneity was high (I2=72.7%), reflecting methodological differences. Meta-analysis of mortality data (13,127 participants) showed that male mortality rates exceeded female mortality rates up until the 90 to 94-years age group. Individual studies reported higher mortality for males at each level of FI, and higher risk of death for males when controlling for age and FI. CONCLUSIONS: The pattern of sex differences in the FI and mortality of older adults was consistent across populations and confirmed a 'male-female health-survival paradox'.

Risk factors for development of primary bladder squamous cell carcinoma.

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients.