Geriatric assessment in hematology scale predicts treatment tolerability in older patients diagnosed with hematological malignancies: The RETROGAH study

Chemotherapy; Geriatric assessment; ToxicityQuimioterapia; Evaluación geriátrica; ToxicidadQuimioteràpia; Avaluació geriàtrica; ToxicitatIntroduction The GAH (Geriatric Assessment in Hematology) scale is a psychometrically valid tool aimed at identifying older patients with hematological malignancies at higher risk of treatment-related toxicity. Our objective in this study was to determine the weights for each dimension of the GAH scale and the cut-off point to reliably predict treatment tolerability in this population, estimated by a weighted receiver operating characteristic (ROC) analysis and quantified by the area under the curve (AUC). Material and Methods The RETROGAH was a retrospective cohort study including 126 patients who had previously participated in the GAH study. Patients were ≥ 65 years old with newly diagnosed myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphoid leukemia (CLL) and treated with standard front-line therapy within three months after having completed the GAH scale. Results The optimal cut-off value of the GAH total score to discriminate patients at higher risk of treatment toxicity was 42, with 68.5% sensitivity and 55.8% specificity. Using this value, 66.1% of patients evaluated were found to develop some type of toxicity. The AUC was 0.6259 (95% CI: 0.512–0.739; p = 0.035). Discussion The GAH scale not only would enable clinicians to individualize therapy based on individual risk of toxicity but also discriminate patients that will benefit most from intensive treatments from those requiring an adapted approach. While futures studies in clinical practice may improve the model and overcome its limitations, the GAH scale should not be used alone when making treatment decisions.This study was supported by Celgene España S.L

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

Aims: 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). Methods and results: 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). Conclusion: 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

Frailty Screening and Impairment Patterns in Older Adults with Cancer: A Dissertation Using the Cancer Aging and Resilience Evaluation (CARE) Registry

Older adults with cancer often have multiple health impairments. Although geriatric assessments are recommended to identify older adult impairments not captured in oncology assessments, impairments are not often evaluated. Thus, patients may undergo treatment without support for impairments associated with adverse outcomes. The objectives were to evaluate the screening performance of skeletal muscle density (SMD) in classifying frailty in older adults with cancer (Aim 1) and to identify and describe geriatric assessment impairment patterns in older adults with gastrointestinal cancers (Aim 2). We used the Cancer Aging and Resilience Evaluation (CARE) registry (University of Alabama at Birmingham). Patients completed the CARE tool, a self-reported geriatric assessment, and responses were used to calculate frailty scores and categorize impairment indicators. SMD was calculated from computed tomography scans (L3 vertebrae), and performance in classifying frailty was evaluated using diagnostic model methods and compared by gender-diabetes status. Using latent class analysis (LCA) with impairment indicators, we identified impairment classes among patients with gastrointestinal malignancies and described classes using impairment probabilities, patient characteristics, and one-year mortality. SMD performed poorly. Area under the receiver operating curve (AUC) estimates were low for all four gender-diabetes subsets (range: 0.58-0.68). Third quartile gender-specific cut-off points for SMD had high sensitivity (0.76-0.89), but low specificity (0.25-0.34). Positive and negative likelihood ratio results indicated that utility was most promising for men with diabetes compared to other subgroups. We identified 6 impairment latent classes (LC): mild impairment (LC1, 28% prevalence); social support impairment (LC2, 12%); weight loss alone (LC3, 16%); impaired, low anxiety/depression (LC4, 23%); impaired with anxiety/depression (LC5, 11%); global impairment (LC6, 11%). One-year mortality risk estimates ranged from 11% (mild impairment) to 44% (global impairment) compared to 14-34% when using frailty categories. In overall and stratified analyses (high- vs. low-risk cancers), mortality estimates for the 3 impaired classes (LC4, LC5, LC6) were greater than the mild impairment class. Work is needed to improve classification of frailty with SMD and to assess performance in other subgroups and populations. The identified geriatric assessment impairment classes can facilitate awareness of impairment clustering and the planning of support services for older adults with cancer.Doctor of Philosoph

Atrial fibrillation and frailty: An observational cohort study using electronic healthcare records

Atrial fibrillation is common in older people, and is associated with increased mortality and stroke. Patients with atrial fibrillation/flutter (AF) also commonly have frailty, which is associated with increased risk of a range of further adverse clinical outcomes. However, there is a lack of evidence on the burden and management of AF in people with frailty. A study using the primary care electronic health records of 536,955 patients aged ≥65 years was conducted to investigate the burden of frailty and AF amongst older people, and their associations with clinical outcomes. A systematic review and meta-analysis was completed to establish the current knowledge base, and to inform the quantitative analyses. Baseline characteristics were described and compared between those with and without AF as well as by frailty category according to the electronic frailty index. Rates of all-cause mortality, stroke, bleeding (intracranial and gastrointestinal), transient ischaemic attack (TIA), and falls were calculated per 1000 person-years, and compared with the non-AF patient population. Cox proportional hazards modelling was used to determine unadjusted and adjusted risk for each clinical outcome and mortality, and presented as hazard ratios (HR) alongside 95% confidence intervals. The association between oral anticoagulation (OAC) prescription stratified by frailty category with clinical outcomes was investigated using Cox proportional hazards modelling. At baseline, 61,177 (11.4%) patients had AF. People with AF had a higher burden of frailty than those without (89.5% vs. 55.3%) and had higher rates of mortality, stroke, TIA and bleeding. Of patients with AF and eligible for OAC, it was prescribed in 53.1% (41.7% in robust, mild frailty 53.2%, moderate 55.6%, severe 53.4%). OAC was associated with a 19% reduction in all-cause mortality (HR 0.81, 95%CI 0.77-0.85) and 22% reduction in stroke (HR 0.78, 0.67-0.92). There was no statistically significant difference in rates of bleeding between those prescribed and not prescribed OAC. For the first time in a large representative cohort of older people, this study quantified the burden of AF and frailty, and their association with a range of clinical outcomes. This study found no evidence that OAC should be withheld on the basis of concomitant frailty

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes

A study of frailty, falls, bone mineral density and fractures among HIV-positive and HIV-negative controls in England and Ireland, the POPPY study

Effective antiretroviral therapy (ART) has prolonged life expectancy among people living with HIV (PLWH) in most parts of Europe, but as PLWH are ageing, this group is now starting to experience signs of compromised health, with particular concerns around possible increased rates of frailty, falls and fractures. In this thesis I use data from the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study (699 older (≥50 years) PLWH, 374 younger (<50 years) PLWH and 304 HIV-negative controls (≥50 years)) to examine some of the challenges of ageing in PLWH in England and Ireland. In particular, I investigate frailty, falls, bone mineral density (BMD), fractures and fracture (hip and major-osteoporotic) risk among PLWH and HIV-negative controls, and examine their associations with demographic, clinical, lifestyle and HIV-specific factors. Results highlight that older PLWH experience increased frailty, a higher prevalence of falls and a greater loss of BMD than younger PLWH and similarly-aged HIV-negative controls. Furthermore, this thesis highlights the importance of demographic characteristics, lifestyle traits, depressive symptoms, physical functioning and HIV-specific factors for the development of frailty, falls and low BMD in PLWH. Among PLWH, I also explore whether the effect of age on the prevalence of frailty could be explained by the effect of HIV parameters by investigating the association of HIV-specific parameters with each of the outcomes considered. Finally, I explore the link between pharmacokinetic (PK) parameters of commonly used nucleoside reverse transcriptase inhibitors (NRTIs) with BMD and with the 10-year probability of fracture. This thesis identified groups at heightened risk for frailty, falls and low BMD, fractures and fracture risk experiencing poor health outcomes against the backdrop of overall improvement of life span among PLWH and aims to inform policy for optimising treatment, tailored to the needs of this population