Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Management of cancer-associated thromboembolism in vulnerable population.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.

Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions.

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

Frailty and sarcopenia within the earliest national Dutch childhood cancer survivor cohort (DCCSS-LATER): a cross-sectional study.

BACKGROUND: Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce, especially in European survivors. The aim of this cross-sectional study was to assess the prevalence of and explore risk factors for pre-frailty, frailty, and sarcopenia in a national cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001. METHODS: Eligible individuals (alive at the time of study, living in the Netherlands, age 18-45 years, and had not previously declined to participate in a late-effects study) from the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort were invited to take part in this cross-sectional study. We defined pre-frailty and frailty according to modified Fried criteria, and sarcopenia according to the European Working Group on Sarcopenia in Older People 2 definition. Associations between these conditions and demographic and treatment-related as well as endocrine and lifestyle-related factors were estimated with two separate multivariable logistic regression models in survivors with any frailty measurement or complete sarcopenia measurements. FINDINGS: 3996 adult survivors of the DCCSS-LATER cohort were invited to participate in this cross-sectional study. 1993 non-participants were excluded due to lack of response or a decline to participate and 2003 (50·1%) childhood cancer survivors aged 18-45 years were included. 1114 (55·6%) participants had complete frailty measurements and 1472 (73·5%) participants had complete sarcopenia measurements. Mean age at participation was 33·1 years (SD  7·2). 1037 (51·8%) participants were male, 966 (48·2%) were female, and none were transgender. In survivors with complete frailty measurements or complete sarcopenia measurements, the percentage of pre-frailty was 20·3% (95% CI 18·0-22·7), frailty was 7·4% (6·0-9·0), and sarcopenia was 4·4% (3·5-5·6). In the models for pre-frailty, underweight (odds ratio [OR] 3·38 [95% CI 1·92-5·95]) and obesity (OR 1·67 [1·14-2·43]), cranial irradiation (OR 2·07 [1·47-2·93]), total body irradiation (OR 3·17 [1·77-5·70]), cisplatin dose of at least 600 mg/m2 (OR 3·75 [1·82-7·74]), growth hormone deficiency (OR 2·25 [1·23-4·09]), hyperthyroidism (OR 3·72 [1·63-8·47]), bone mineral density (Z score ≤-1 and >-2, OR 1·80 [95% CI 1·31-2·47]; Z score ≤-2, OR 3·37 [2·20-5·15]), and folic acid deficiency (OR 1·87 [1·31-2·68]) were considered significant. For frailty, associated factors included age at diagnosis between 10-18 years (OR 1·94 [95% CI 1·19-3·16]), underweight (OR 3·09 [1·42-6·69]), cranial irradiation (OR 2·65 [1·59-4·34]), total body irradiation (OR 3·28 [1·48-7·28]), cisplatin dose of at least 600 mg/m2 (OR 3·93 [1·45-10·67]), higher carboplatin doses (per g/m2; OR 1·15 [1·02-1·31]), cyclophosphamide equivalent dose of at least 20 g/m2 (OR 3·90 [1·65-9·24]), hyperthyroidism (OR 2·87 [1·06-7·76]), bone mineral density Z score ≤-2 (OR 2·85 [1·54-5·29]), and folic acid deficiency (OR 2·04 [1·20-3·46]). Male sex (OR 4·56 [95%CI 2·26-9·17]), lower BMI (continuous, OR 0·52 [0·45-0·60]), cranial irradiation (OR 3·87 [1·80-8·31]), total body irradiation (OR 4·52 [1·67-12·20]), hypogonadism (OR 3·96 [1·40-11·18]), growth hormone deficiency (OR 4·66 [1·44-15·15]), and vitamin B12 deficiency (OR 6·26 [2·17-1·81]) were significantly associated with sarcopenia. INTERPRETATION: Our findings show that frailty and sarcopenia occur already at a mean age of 33 years in childhood cancer survivors. Early recognition and interventions for endocrine disorders and dietary deficiencies could be important in minimising the risk of pre-frailty, frailty, and sarcopenia in this population. FUNDING: Children Cancer-free Foundation, KiKaRoW, Dutch Cancer Society, ODAS Foundation.

Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer: Results From the Hurria Older Patients Prospective Study.

PURPOSE: Older breast cancer survivors are at increased risk of clinical decline after adjuvant chemotherapy. This study aimed to evaluate whether inflammatory markers assessed before adjuvant chemotherapy are associated with chemotherapy-induced clinical decline in a population of fit older adults with breast cancer. METHODS: In a prospective study of women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy, we measured interleukin-6 (IL-6) and C-reactive protein (CRP) prechemotherapy (T1). We assessed frailty status, using a Deficit Accumulation Index (DAI; categorized as robust, prefrail, and frail), at T1 and postchemotherapy (T2). The population of interest was robust women at T1. The primary outcome was chemotherapy-induced decline in frailty status, defined as decline in DAI from robust (T1) to prefrail or frail (T2). Multivariable logistic regression was used to examine the association between inflammatory markers and the primary outcome, adjusted for sociodemographic and clinical characteristics. RESULTS: Of the 295 robust women at T1, 76 (26%) experienced chemotherapy-induced decline in frailty status, among whom 66% had high IL-6, 63% had high CRP, and 46% had high IL-6 and CRP at T1. After adjusting for sociodemographic and clinical characteristics, women with high IL-6 and CRP had a > three-fold (odds ratio, 3.52; 95% CI, 1.55 to 8.01; P = .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP. CONCLUSION: In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.

Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial.

INTRODUCTION: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life. METHODS AND ANALYSIS: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN17973108, NCT03720041.

Frailty and checkpoint inhibitor toxicity in older patients with melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) that range from mild to life-threatening. Age itself does not seem to be a predictor for the occurrence of irAEs. It is unknown whether frailty plays a role in the occurrence of irAEs. Therefore, the authors assessed whether irAEs and their sequelae occur more often in frail patients than in fit patients according to the Geriatric 8 (G8) assessment. METHODS: Patients with melanoma aged 70 years and older who were about to start ICI therapy and were screened with the G8 assessment were enrolled in this prospective, observational study. Patients were classified by the G8 as either fit or frail. The primary outcome was the occurrence of grade ≥3 irAEs. RESULTS: In total, 92 patients were included for statistical analyses, 26 (29%) of whom were classified as frail. Grade ≥3 irAEs occurred in 20% of patients. There was no significant difference in the occurrence of grade ≥3 irAEs between fit and frail patients (17% vs 27%; P = .26). Frail patients were admitted to the hospital because of irAEs significantly more often than fit patients (29% vs 54%; P = .02) and showed a trend toward increased length of hospitalization (5 vs 8 days; P = .06) and more frequent use of immunosuppressants or ICI discontinuation for irAEs (36% vs 58%; P = .06). CONCLUSIONS: Although frailty appears to be unrelated to the occurrence of severe irAEs, it is an indicator of irAE-related adverse sequelae, such as hospital admission. Screening for frailty can be of added value in the shared decision-making process for older patients who qualify for ICI treatment.

Influence of Long-term Nonaspirin NSAID Use on Risk of Frailty in Men ≥60 Years: The Physicians' Health Study.

BACKGROUND: Inflammation is a central pathway leading to frailty but whether commonly used nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent frailty is unknown. METHODS: Prospective cohort study of male physicians ≥60 who participated in the Physicians' Health Study. Annual questionnaires collected data on NSAID use, lifestyle, and morbidity. Average annual NSAID use was categorized as 0 days/year, 1-12 days/year, 13-60 days/year, and >60 days/year. Frailty was assessed using a validated 33-item frailty index. Propensity score inverse probability of treatment weighting was used to address confounding by indication and logistic regression models estimated odds ratios (ORs) of prevalent frailty according to nonaspirin NSAID use. RESULTS: A total of 12 101 male physicians were included (mean age 70 ± 7 years, mean follow-up 11 years). Reported NSAID use was 0 days/year for 2 234, 1-12 days/year for 5 812, 13-60 days/year for 2 833, and >60 days/year for 1 222 participants. A total of 2 413 participants (20%) were frail. Higher self-reported NSAID use was associated with greater alcohol use, smoking, arthritis, hypertension, and heart disease, while less NSAID use was associated with coumadin use and prior bleeding. After propensity score adjustment, all characteristics were balanced. ORs (95% confidence intervals) of prevalent frailty were 0.90 (0.80-1.02), 1.02 (0.89-1.17), and 1.26 (1.07-1.49) for average NSAID use of 1-12 days/year, 13-60 days/year, and >60 days/year, compared to 0 days/year (p-trend < .001). CONCLUSIONS: Long-term use of NSAIDs at high frequency is associated with increased risk of frailty among older men. Additional study is needed to understand the role of anti-inflammatory medication in older adults and its implication for overall health.

Chronic Polypharmacy with Increasing Drug Burden Index Exacerbates Frailty and Impairs Physical Function, with Effects Attenuated by Deprescribing, in Aged Mice.

Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person's total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.

Frailty and Risk of Serious Infections in Biologic-treated Patients With Inflammatory Bowel Diseases.

BACKGROUND: Identifying biologic-treated patients with inflammatory bowel diseases (IBDs) at higher risk of serious infections is a priority. We conducted a retrospective cohort study evaluating frailty and risk of serious infections in biologic-treated patients with IBD. METHODS: Using an administrative claims database, we identified biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation. Using a validated claims-based hospital frailty risk scoring system, patients were classified as frail and nonfrail. We compared the risk of serious infections (infections requiring hospitalization) between frail and nonfrail patients using Cox proportional hazard analysis adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates. RESULTS: We included 5987 biologic-treated patients with IBD (4881 on TNFα antagonists, 1106 on vedolizumab), of whom 2350 (39.3%) were classified as frail; over 7115 person-years of follow-up was included, and 520 patients developed serious infection. Frailty was not associated with increased risk of serious infection (adjusted hazard ratio [aHR], 1.12; 95% CI, 0.93-1.36), whereas advanced age (older than 60 years), high comorbidity burden, corticosteroid use, opiate use, and prior serious infection were associated with increased risk of serious infection. On stratified analysis, frailty was associated with increased risk of serious infections in vedolizumab-treated patients (aHR, 1.69; 95% CI, 1.03-2.79) but not in TNFα antagonist-treated patients (aHR, 1.03; 95% CI, 0.83-1.27). CONCLUSIONS: In biologic-treated patients with IBD, frailty assessed using a claims-based frailty index was not independently associated with increased risk of serious infections. Future studies evaluating objective and biological measures of frailty are warranted to risk-stratify older patients with IBD.

[Impact of antineoplastic drugs on the nutritional status of older patients with cancer. Can the medical oncologist minimize the impact of these drugs on the nutrirional status of these patients?] / Repercusión de los fármacos antineoplásicos sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo médico minimizar el impacto de estos fármacos sobre el estado nutricional del enfermo mayor?

INTRODUCTION: Aging is associated, per se, with the loss of functional reserve of different organs and systems, a greater risk of vulnerability and frailty, sarcopenia and malnutrition, a reality that is extended to cancer patients. There are several factors that are associated with malnutrition in the elderly individual, such as the difficulty in regulating food intake, loss of appetite and anorexia associated with age, alteration of the senses of taste and smell, dysgeusia or economic problems. In the case of the cancer patient, other factors are added to these factors, such as: type of tumor; tumor stage; evolutionary moment of the disease; and baseline situation. Many therapeutic strategies used against the tumor, such as surgery, treatment with radiotherapy (concomitant or not with chemotherapy) and treatment with antitumor drugs influence also the risk of malnutrition. Thus, for example, concomitant chemo-radiation therapy in head and neck tumors, in lung cancer or in pelvic tumors represents a high nutritional risk antitumor therapy. Some of the repercussions of malnutrition in the oncological elderly are severe. Thus, for example, malnutrition in these individuals is associated with: worse survival; increased risk of early discontinuation of chemotherapy treatment; increased risk of chemotherapy toxicity; increased toxicity from other antitumor drugs; and increased risk of mortality during chemotherapy treatment. Taking this information into account, it is essential: to optimize the nutritional status in older patients with cancer prior to starting a systemic antitumor treatment; to carry out a nutritional follow-up throughout the treatment; and to offer early and intense management of malnutrition once it appears, with the purpose of minimizing the impact of antitumor drugs in older patients with cancer. Early management of malnutrition could improve drugs tolerance and increase the health-related quality of life in these patients.

INTRODUCCIÓN: El envejecimiento se asocia a la pérdida de reserva funcional de distintos órganos y sistemas, a un mayor riesgo de vulnerabilidad y de fragilidad, a la sarcopenia y a la malnutrición, realidad que se hace extensible a los pacientes oncológicos. Varios factores se asocian a la malnutrición en el individuo de edad avanzada: dificultad para regular la ingesta de alimentos, pérdida de apetito y anorexia asociadas a la edad, alteración de los sentidos del gusto y olfato, disgeusia o problemas económicos. En el caso del paciente oncológico, a estos factores se añaden otros como: tipo de tumor; estadio tumoral; momento evolutivo de la enfermedad; y situación basal. También las distintas estrategias terapéuticas utilizadas frente al tumor, como cirugía, tratamiento con radioterapia (concomitante o no a quimioterapia) y tratamiento con fármacos antitumorales influyen en el riesgo de malnutrición. Así, por ejemplo, la quimio-radioterapia concomitante en tumores de cabeza y cuello, en cáncer de pulmón o en tumores de localización pélvica, representa una terapia antitumoral de alto riesgo nutricional. Algunas de las repercusiones de la malnutrición en el anciano oncológico son severas. La malnutrición en estos individuos se asocia a: peor supervivencia; mayor riesgo de interrupción precoz del tratamiento con quimioterapia; aumento en el riesgo de toxicidad de la quimioterapia; mayor toxicidad por otros fármacos antitumorales; y riesgo incrementado de mortalidad durante el tratamiento con quimioterapia. Teniendo en cuenta esta información, resulta fundamental optimizar el estado nutricional en el anciano oncológico previo al inicio de un tratamiento antitumoral sistémico, hacer un seguimiento a lo largo del tratamiento y ofrecer un manejo precoz e intenso de la malnutrición una vez aparezca, con la finalidad de minimizar el impacto de los fármacos antitumorales en el anciano, de mejorar la tolerancia de tales fármacos y aumentar la calidad de vida relacionada con la salud en estos pacientes.

Reducing medicine-induced deterioration and adverse reactions (ReMInDAR) trial: study protocol for a randomised controlled trial in residential aged-care facilities assessing frailty as the primary outcome.

INTRODUCTION: Many medicines have adverse effects which are difficult to detect and frequently go unrecognised. Pharmacist monitoring of changes in signs and symptoms of these adverse effects, which we describe as medicine-induced deterioration, may reduce the risk of developing frailty. The aim of this trial is to determine the effectiveness of a 12-month pharmacist service compared with usual care in reducing medicine-induced deterioration, frailty and adverse reactions in older people living in aged-care facilities in Australia. METHODS AND ANALYSIS: The reducing medicine-induced deterioration and adverse reactions trial is a multicentre, open-label randomised controlled trial. Participants will be recruited from 39 facilities in South Australia and Tasmania. Residents will be included if they are using four or more medicines at the time of recruitment, or taking more than one medicine with anticholinergic or sedative properties. The intervention group will receive a pharmacist assessment which occurs every 8 weeks. The pharmacists will liaise with the participants' general practitioners when medicine-induced deterioration is evident or adverse events are considered serious. The primary outcome is a reduction in medicine-induced deterioration from baseline to 6 and 12 months, as measured by change in frailty index. The secondary outcomes are changes in cognition scores, 24-hour movement behaviour, grip strength, weight, percentage robust, pre-frail and frail classification, rate of adverse medicine events, health-related quality of life and health resource use. The statistical analysis will use mixed-models adjusted for baseline to account for repeated outcome measures. A health economic evaluation will be conducted following trial completion using data collected during the trial. ETHICS AND DISSEMINATION: Ethics approvals have been obtained from the Human Research Ethics Committee of University of South Australia (ID:0000036440) and University of Tasmania (ID:H0017022). A copy of the final report will be provided to the Australian Government Department of Health. TRIAL REGISTRATION NUMBER: Australian and New Zealand Trials Registry ACTRN12618000766213.

Medication burden and frailty in older adults with intellectual disability: An observational cross-sectional study.

PURPOSE: Recently, efforts have been made to quantify frailty among older adults with intellectual disability (ID). Medication exposure is associated with frailty among older adults without ID. However, there is little research on this association among older adults with ID. The aim of this study was to examine specifically in people with ID the association between frailty and medication exposure, including anticholinergic and sedative medication exposure. METHODS: Data were drawn from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a nationally representative study of older adults with ID in Ireland. A modified version of Fried's frailty phenotype was constructed. Drug burden measures were polypharmacy, Drug Burden Index (DBI), Anticholinergic Cognitive Burden (ACB) and Sedative Load Model. Multinomial logistic regression was used to calculate odds ratios (ORs) and identify associations between frailty and drug burden. RESULTS: This study included 570 participants with ID. Excessive polypharmacy (use of ≥10 medications) was significantly associated with being pre-frail (P = .017; OR = 2.56; 95% confidence interval [CI] 1.19-5.50) and frail (P < .001; OR 7.13; 95% CI 2.81-18.12), but DBI, ACB or Sedative Load score were not significantly associated with frailty status (P > .05). CONCLUSIONS: This is the first study to examine frailty and its association with medication use including anticholinergic and sedative medication burden among older adults with ID. Further research is required to investigate frailty as measured by other frailty models in relation to medication burden in older adults with ID.

Frailty syndrome is associated with changes in peripheral inflammatory markers in prostate cancer patients undergoing androgen deprivation therapy.

OBJECTIVE: To evaluate the role of peripheral inflammation (leukocyte differential count, the proinflammatory cytokines IL-beta, TNF-α, IL-6, IL-8, and the inflammatory markers fibrinogen and C-reactive protein [CRP]) in frailty syndrome in patients with prostate cancer (CaP) undergoing antiandrogen therapy (ADT). METHODS: A total of 46 men between 51 and 92 years of age with CaP and receiving ADT were classified as frail, prefrail or robust according to the Fried scale. A geriatric assessment was performed, based on the Minimental State Examination for cognitive function, the Barthel index for basic activities of daily living, the Yesavage scale for geriatric depression, and the Athens insomnia scale. In addition, blood samples were collected to assess peripheral inflammation biomarkers including proinflammatory cytokines, fibrinogen, CRP and leukocyte differential count, as well as other biochemical and hematological parameters. RESULTS: A significant negative correlation between the severity of frailty syndrome and lymphocyte count was observed (P < 0.01). The concentration of IL-6 (P < 0.05), CRP (P < 0.05), and fibrinogen (P < 0.01) were significantly associated with frailty syndrome, but not of TNF-α, IL-beta, or IL-8. The severity of frailty syndrome was not dependent upon the clinical disease stage at diagnosis, the time elapsed since CaP diagnosis, the presence of metastases, or prostatectomy. CONCLUSIONS: Further research into the role of leukocyte subtypes and peripheral inflammation and the associated adverse outcomes in patients with CaP under ADT is warranted in order to tailor interventions aimed at reducing symptoms of frailty syndrome, such as loss of muscle strength and low physical activity.

Polypharmacy is associated with frailty in Japanese community-dwelling older adults.

AIM: The association between polypharmacy and the development of frailty is unknown. The present study assessed the longitudinal relationship between polypharmacy and frailty risk in Japanese community-dwelling older adults. METHODS: Participants included 299 non-frail older Japanese adults aged 65-81 years who participated in both baseline and follow-up examinations of a longitudinal study of aging (mean duration 6.2 years). At baseline examination, all prescribed and non-prescribed medications used during the previous 2 weeks were confirmed and coded by physicians. Frailty was diagnosed according to frailty criteria, and included shrinking, exhaustion, low activity, low grip strength and low gait speed. The relationship between frailty and the number of medications was assessed using multiple logistic regression analysis. The logistic regression model was used to control for potential confounders, including age at baseline, sex, body fat, total physical activity, education, employment, current smoking and number of comorbidities. RESULTS: The percentage of participants who developed frailty during follow up was 5.1% in those taking five or fewer medications, and 22.5% in those taking six or more medications. The fully adjusted odds ratio for frailty among participants taking six or more medications was 5.55 (95% confidence interval 2.17-14.22). CONCLUSIONS: Polypharmacy appears to be a significant risk factor for the development of frailty in older Japanese adults. Geriatr Gerontol Int 2018; 18: 1497-1500.

Persisting adverse body composition changes 2 years after cessation of androgen deprivation therapy for localised prostate cancer.

OBJECTIVE: Hypogonadism from androgen deprivation therapy (ADT) for prostate cancer causes adverse body composition changes associated with insulin resistance and decreased quality of life (QoL). Our objective was to assess whether adverse body composition changes improve after cessation of ADT. DESIGN: Prospective case-control study in a tertiary referral hospital. Thirty-four men newly commencing ADT (cases, median age: 67.6 years (interquartile range: 64.6-72.0)) and 29 age-matched (70.6 years (65.3-72.9)) prostate cancer controls not on ADT were assessed 2 years after cessation of ADT (median: 4.4 years). METHODS: Serum testosterone, body composition, handgrip strength, frailty and QoL were measured. Using a mixed model, the mean adjusted differences (MADs (95% CI)) between groups from baseline to study end are reported. RESULTS: Twenty-seven cases and 19 controls completed the study. Median duration of ADT was 2.3 years (interquartile range: 1.8-3.1). Two years after cessation of ADT, total testosterone remained lower (MAD: -3.4 nmol/L (-6.3 to -0.5), P < 0.022), fat mass (2214 g (490-3933), P = 0.025) and insulin resistance (homeostasis model assessment of insulin resistance: 0.69 (0.31-1.07), P < 0.001) remained higher in cases, whereas lean mass (-1450 g (-2259 to -640), P < 0.001) and physical component of QoL remained lower than controls (-11.9 (-16.4 to -7.4), P < 0.001). CONCLUSION: Two years after ADT cessation, metabolically adverse changes in body composition, increased insulin resistance and reduced QoL persisted. This may be related to incomplete testosterone recovery. Persisting adverse effects need to be considered in the risk to benefit assessment of ADT and proactive mitigation should continue after cessation of treatment.