Deprescribing Opportunities for Frail Residents of Nursing Homes: A Multicenter Study in Australia, China, Japan, and Spain.

OBJECTIVE: Deprescribing opportunities may differ across health care systems, nursing home settings, and prescribing cultures. The objective of this study was to compare the prevalence of STOPPFrail medications according to frailty status among residents of nursing homes in Australia, China, Japan, and Spain. DESIGN: Secondary cross-sectional analyses of data from 4 cohort studies. SETTING AND PARTICIPANTS: A total of 1142 residents in 31 nursing homes. METHODS: Medication data were extracted from resident records. Frailty was assessed using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Chi-square tests and prevalence ratios (PRs) were used to compare STOPPFrail medication use across cohorts. RESULTS: In total, 84.7% of non-frail, 95.6% of frail, and 90.6% of most-frail residents received ≥1 STOPPFrail medication. Overall, the most prevalent STOPPFrail medications were antihypertensives (53.0% in China to 73.3% in Australia, P < .001), vitamin D (nil in China to 52.7% in Australia, P < .001), lipid-lowering therapies (11.1% in Japan to 38.9% in Australia, P < .001), aspirin (13.5% in Japan to 26.2% in China, P < .001), proton pump inhibitors (2.1% in Japan to 32.0% in Australia, P < .001), and antidiabetic medications (12.3% in Japan to 23.5% in China, P = .010). Overall use of antihypertensives (PR, 1.15; 95% CI, 1.06-1.25), lipid-lowering therapies (PR, 1.78; 95% CI, 1.45-2.18), aspirin (PR, 1.31; 95% CI, 1.04-1.64), and antidiabetic medications (PR, 1.31; 95% CI, 1.00-1.72) were more prevalent among non-frail and frail residents compared with most-frail residents. Antihypertensive use was more prevalent with increasing frailty in China and Japan, but less prevalent with increasing frailty in Australia. Antidiabetic medication use was less prevalent with increasing frailty in China and Spain but was consistent across frailty groups in Australia and Japan. CONCLUSIONS AND IMPLICATIONS: There were overall and frailty-specific variations in prevalence of different STOPPFrail medications across cohorts. This may reflect differences in prescribing cultures, application of clinical practice guidelines in the nursing home setting, and clinician or resident attitudes toward deprescribing.

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.

Association of the Drug Burden Index (DBI) exposure with outcomes: A systematic review.

BACKGROUND: The Drug Burden Index (DBI) measures an individual's total exposure to anticholinergic and sedative medications. This systematic review aimed to investigate the association of the DBI with clinical and prescribing outcomes in observational pharmaco-epidemiological studies, and the effect of DBI exposure on functional outcomes in pre-clinical models. METHODS: A systematic search of nine electronic databases, citation indexes and gray literature was performed (April 1, 2007-December 31, 2022). Studies that reported primary data on the association of the DBI with clinical or prescribing outcomes conducted in any setting in humans aged ≥18 years or animals were included. Quality assessment was performed using the Joanna Briggs Institute critical appraisal tools and the Systematic Review Centre for Laboratory animal Experimentation risk of bias tool. RESULTS: Of 2382 studies screened, 70 met the inclusion criteria (65 in humans, five in animals). In humans, outcomes reported included function (n = 56), cognition (n = 20), falls (n = 14), frailty (n = 7), mortality (n = 9), quality of life (n = 8), hospitalization (n = 7), length of stay (n = 5), readmission (n = 1), other clinical outcomes (n = 15) and prescribing outcomes (n = 2). A higher DBI was significantly associated with increased falls (11/14, 71%), poorer function (31/56, 55%), and cognition (11/20, 55%) related outcomes. Narrative synthesis was used due to significant heterogeneity in the study population, setting, study type, definition of DBI, and outcome measures. Results could not be pooled due to heterogeneity. In animals, outcomes reported included function (n = 18), frailty (n = 2), and mortality (n = 1). In pre-clinical studies, a higher DBI caused poorer function and frailty. CONCLUSIONS: A higher DBI may be associated with an increased risk of falls and decreased function and cognition. Higher DBI was inconsistently associated with increased mortality, length of stay, frailty, hospitalization or reduced quality of life. Human observational findings with respect to functional outcomes are supported by preclinical interventional studies. The DBI may be used as a tool to identify older adults at higher risk of harm.

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.

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Geriatric Medicine Principles in Conservative Kidney Management: Frailty, Functional Assessments, and Selective Deprescribing.

Conservative kidney management is a nondialytic treatment option for advanced chronic kidney disease that involves interventions to delay kidney function loss, medications to treat symptoms, and psychosocial support for patients and their loved ones. Several geriatric medicine principles are applicable to patients who are considering or receiving conservative kidney management, including the integration of physical, psychological, and social factors into medical care and medical decisions; careful review of medication lists with selective deprescribing; and screening for geriatric syndromes such as frailty and functional impairment. In this review, we discuss how functional and frailty assessments as well as selective deprescribing can be useful for patients considering or receiving conservative kidney management.

Frailty and uptake of angiotensin receptor neprilysin inhibitor for heart failure with reduced ejection fraction.

BACKGROUND: Frail older adults may be less likely to receive guideline-directed medical therapy (GDMT)-renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists-for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF. METHODS: Using 2015-2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index. Logistic regression was used to identify clinical characteristics associated with ARNI initiation. Cox proportional hazards regression was used to examine the association of GDMT use in 2015 and death or heart failure hospitalization in 2016-2019. RESULTS: Among 147,506-180,386 beneficiaries with HFrEF (mean age: 77 years; 27% women; 42.6-49.1% frail) in 2015-2019, the proportion of patients receiving ARNI increased in both non-frail (0.4%-16.4%) and frail (0.3%-13.7%) patients (p for yearly-trend-by-frailty = 0.970). Among those not receiving a renin-angiotensin system blocker, patients with age ≥ 85 years (odds ratio [95% CI], 0.89 [0.80-0.99]), dementia (0.88 [0.81-0.96]), and frailty (0.87 [0.81-0.94]) were less likely to initiate ARNI. The proportion of patients receiving all 3 GDMT classes increased in non-frail patients (22.0%-27.0%) but changed minimally in frail patients (19.6%-21.8%). Regardless of frailty status, treatment with at least 1 class of GDMT was associated with lower death or heart failure hospitalization than no GDMT medications (hazard ratio [95% CI], 0.94 [0.91-0.97], 0.92 [0.89-0.94], 0.94 [0.91-0.97] for 1, 2, and 3 classes, respectively). CONCLUSIONS: Our results suggest an evidence-practice gap in the use of ARNI and GDMT in Medicare beneficiaries with HFrEF, particularly those with frailty. Efforts to narrow this gap are needed to reduce the burden of HFrEF in older adults.

Protectin DX as a therapeutic strategy against frailty in mice.

Frailty in aging is driven by the dysregulation of multiple biological pathways. Protectin DX (PDX) is a docosahexaenoic acid (DHA)-derived molecule that alleviates many chronic inflammatory disorders, but its potential effects on frailty remain unknown. Our goal is to identify age-related impairments in metabolic systems and to evaluate the therapeutic potential of PDX on frailty, physical performance, and health parameters. A set of 22-month-old C57BL/6 male and female mice were assigned to vehicle (Old) or PDX daily gavage treatment for 9 weeks, whereas 6-month-old (Adult) mice received only vehicle. Forelimb and hindlimb strength, endurance, voluntary wheel activity and walking speed determined physical performance and were combined with a frailty index score and body weight loss to determine frailty status. Our data shows that old vehicle-treated mice from both sexes had body weight loss paralleling visceromegaly, and Old females also had impaired insulin clearance as compared to the Adult group. Aging was associated with physical performance decline together with higher odds of frailty development. There was also age-driven mesangial expansion and glomerular hypertrophy as well as bone mineral density loss. All of the in vivo and in vitro impairments observed with aging co-occurred with upregulation of inflammatory pathways and Myc signaling as well as downregulation of genes related to adipogenesis and oxidative phosphorylation in liver. PDX attenuated the age-driven physical performance (strength, exhaustion, walking speed) decline, promoted robustness, prevented bone losses and partially reversed changes in hepatic expression of Myc targets and metabolic genes. In conclusion, our data provides evidence of the beneficial therapeutic effect of PDX against features of frailty in mice. Further studies are warranted to investigate the mechanisms of action and the potential for human translation.

Utility of the frailty score for predicting prognosis and individualizing treatment intensity in elderly patients with diffuse large B cell lymphoma.

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients' frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70-79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL.

Attitude towards deprescribing and its association with frailty and complexity of medication regimen: A survey of older inpatients in a district health board in New Zealand.

BACKGROUND: Older inpatients, particularly those with frailty, have increased exposure to complex medication regimens. It is not known whether frailty and complexity of medication regimens influence attitudes toward deprescribing. This study aimed to investigate (1) older inpatients' attitudes toward deprescribing; (2) if frailty and complexity of medication regimen influence attitudes and willingness to deprescribe - a relationship that has not been investigated in previous studies. METHODS: In this cross-sectional study, older adults (≥ 65 years) recruited from general medicine and geriatric services in a New Zealand hospital completed the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Hospital frailty risk score (HFRS) was calculated using diagnostic codes and other relevant information present at the time of index hospital admission; higher scores indicate higher frailty risk. Medication regimen complexity was quantified using the medication regimen complexity index (MRCI); higher scores indicate greater complexity. Logistic regression analysis was used to identify predictors of attitudes and willingness to deprescribe. RESULTS: A total of 222 patients were included in the study, the median age was 83 years and 63% were female. One in two patients reported feeling they were taking too many medications, and 1 in 5 considered their medications burdensome. Almost 3 in 4 (73%) wanted to be involved in decision-making about their medications, and 4 in 5 (84%) were willing to stop one or more of their medications if their prescriber said it was possible. Patients with higher MRCI had increased self-reported medication burden (adjusted odds ratio (AOR) 2.6, 95% CI 1.29, 5.29) and were more interested in being involved in decision-making about their medications (AOR 1.8, CI 0.99, 3.42) than those with lower MRCI. Patients with moderate HFRS had lower odds of willingness to deprescribe (AOR 0.45, CI 0.22,0.92) compared to the low-risk group. Female patients had a lower desire to be involved in decision-making. The oldest old age group( > 80 years) had lower self-reported medication burden and were less likely to want to try stopping their medications. CONCLUSION: Most older inpatients wanted to be involved in decision-making about their medications and were willing to stop one or more medications if proposed by their prescriber. Medication complexity and frailty status influence patients' attitudes toward deprescribing and thus should be taken into consideration when making deprescribing decisions. Further research is needed to investigate the relationship between frailty and the complexity of medication regimens.

Family Conferences to Facilitate Deprescribing in Older Outpatients With Frailty and With Polypharmacy: The COFRAIL Cluster Randomized Trial.

Importance: For older adults with frailty syndrome, reducing polypharmacy may have utility as a safety-promoting treatment option. Objective: To investigate the effects of family conferences on medication and clinical outcomes in community-dwelling older adults with frailty receiving polypharmacy. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from April 30, 2019, to June 30, 221, at 110 primary care practices in Germany. The study included community-dwelling adults aged 70 years or older with frailty syndrome, daily use of at least 5 different medications, a life expectancy of at least 6 months, and no moderate or severe dementia. Interventions: General practitioners (GPs) in the intervention group received 3 training sessions on family conferences, a deprescribing guideline, and a toolkit with relevant nonpharmacologic interventions. Three GP-led family conferences for shared decision-making involving the participants and family caregivers and/or nursing services were subsequently held per patient at home over a period of 9 months. Patients in the control group received care as usual. Main Outcomes and Measures: The primary outcome was the number of hospitalizations within 12 months, as assessed by nurses during home visits or telephone interviews. Secondary outcomes included the number of medications, the number of European Union list of the number of potentially inappropriate medication (EU[7]-PIM) for older people, and geriatric assessment parameters. Both per-protocol and intention-to-treat analyses were conducted. Results: The baseline assessment included 521 individuals (356 women [68.3%]; mean [SD] age, 83.5 [6.17] years). The intention-to-treat analysis with 510 patients showed no significant difference in the adjusted mean (SD) number of hospitalizations between the intervention group (0.98 [1.72]) and the control group (0.99 [1.53]). In the per-protocol analysis including 385 individuals, the mean (SD) number of medications decreased from 8.98 (3.56) to 8.11 (3.21) at 6 months and to 8.49 (3.63) at 12 months in the intervention group and from 9.24 (3.44) to 9.32 (3.59) at 6 months and to 9.16 (3.42) at 12 months in the control group, with a statistically significant difference at 6 months in the mixed-effect Poisson regression model (P = .001). After 6 months, the mean (SD) number of EU(7)-PIMs was significantly lower in the intervention group (1.30 [1.05]) than in the control group (1.71 [1.25]; P = .04). There was no significant difference in the mean number of EU(7)-PIMs after 12 months. Conclusions and Relevance: In this cluster randomized clinical trial with older adults taking 5 or more medications, the intervention consisting of GP-led family conferences did not achieve sustainable effects in reducing the number of hospitalizations or the number of medications and EU(7)-PIMs after 12 months. Trial Registration: German Clinical Trials Register: DRKS00015055.

The management of polypharmacy in people living with HIV.

Antiretroviral therapy (ART) has modified the prognosis of HIV which has evolved into a chronic condition. People living with HIV (PLWH) are living longer presenting an increased number of comorbidities leading to polypharmacy. Literature on the prevalence, associated factors, drug-drug interactions (DDIs), effects on ART-outcomes, geriatric conditions, and nutritional status together with health-interventions aimed to reduce it is presented in this review. A literature search was conducted on the MEDLINE database for all relevant English- and Spanish-language studies since 2006. Studies providing data of interest were identified and ordered in groups: (i) prevalence and associated factors (n = 37), (ii) DDIs (n = 19), (iii) Effects on ART-outcomes (n = 12), (iv) Effects on health conditions (n = 13), and (V) Health-interventions to assess and/or reduce it (n = 9). Polypharmacy occurs in 9-91% of PLWH (2.6-19.5% affected by severe polypharmacy). Main factors associated with polypharmacy are older age, a higher number of comorbidities, frailty, deteriorated renal function, and previous hospitalizations. DDIs were present in 19.15-84% of cases (1.3-12.2% for the most severe types). Mainly involved non-ART drugs were antihypertensives, statins, antithrombotic agents, corticosteroids, divalent cations, and antiacids. Polypharmacy can affect ART selection, adherence, and outcomes and has been related to some geriatric conditions such as falls, frailty, and poor nutritional status. Potentially prescribing issues are present in up to 87.9% of cases according to the STOPP-START and Beers criteria and some pharmacist-led interventions have been shown to reduce it. Considering these findings, polypharmacy should be considered a clinical concern in this population and treatment-optimization programs are needed to reduce its burden.

Deprescribing Anticholinergic and Sedative Drugs to Reduce Polypharmacy in Frail Older Adults Living in the Community: A Randomized Controlled Trial.

BACKGROUND: Polypharmacy is associated with poor outcomes in older adults. Targeted deprescribing of anticholinergic and sedative medications may improve health outcomes for frail older adults. Our pharmacist-led deprescribing intervention was a pragmatic 2-arm randomized controlled trial stratified by frailty. We compared usual care (control) with the intervention of pharmacists providing deprescribing recommendations to general practitioners. METHODS: Community-based older adults (≥65 years) from 2 New Zealand district health boards were recruited following a standardized interRAI needs assessment. The Drug Burden Index (DBI) was used to quantify the use of sedative and anticholinergic medications for each participant. The trial was stratified into low, medium, and high-frailty. We hypothesized that the intervention would increase the proportion of participants with a reduction in DBI ≥ 0.5 within 6 months. RESULTS: Of 363 participants, 21 (12.7%) in the control group and 21 (12.2%) in the intervention group had a reduction in DBI ≥ 0.5. The difference in the proportion of -0.4% (95% confidence interval [CI]: -7.9% to 7.0%) provided no evidence of efficacy for the intervention. Similarly, there was no evidence to suggest the effectiveness of this intervention for participants of any frailty level. CONCLUSION: Our pharmacist-led medication review of frail older participants did not reduce the anticholinergic/sedative load within 6 months. Coronavirus disease 2019 (COVID-19) lockdown measures required modification of the intervention. Subgroup analyses pre- and post-lockdown showed no impact on outcomes. Reviewing this and other deprescribing trials through the lens of implementation science may aid an understanding of the contextual determinants preventing or enabling successful deprescribing implementation strategies.

Clinical frailty and polypharmacy in older emergency critical care patients: a single-centre retrospective case series.

BACKGROUND AND OBJECTIVES: Admission of complex and frail patients to critical care units is common. Little is known about the relationship between clinical frailty and polypharmacy measures in critical care patients or how a critical care admission affects polypharmacy.We sought to: (1) Describe the extent and relationship between clinical frailty and polypharmacy in a cohort of older emergency general critical care patients, and to (2) Describe the effect of the critical care pathway on patient polypharmacy measures. METHODS: A retrospective evaluation was undertaken in all patients ≥70 years of age, admitted as emergencies to the general critical care units of a single large UK academic hospital, over a 2-year period (March 2016 to February 2018) (n=762). Patient Clinical Frailty Scale (CFS) and polypharmacy measures on admission were described and association was tested. Medication changes and documentation on care transitions were analysed in a randomly selected convenience cohort of critical care survivors (n=77). RESULTS: On admission patients had a median of 9 (5;12) medicines, of which a median of 3 (2;5) were high-risk medicines. Polypharmacy (5-9 medicines) and hyperpolypharmacy (≥10 medicines) occurred in 80.7% (615/762) and 43.2% (329/762) of patients, respectively. A degree of frailty was the standard (median CFS 4 (3;5)) with 45.7% (348/762) CFS 4-5 and 20% (153/762) CFS ≥6. The patient median CFS increased by 1 with polypharmacy classification increments (p<0.001). In the survivor cohort, a median of 6 (4;8) and 5 (4;8) medication changes occurred on critical care and hospital discharges, respectively. A minority of patients had detailed medication continuity plans on care transitions. CONCLUSIONS: Polypharmacy and frailty were very common in this UK single-centre cohort of older emergency critical care patients. There was a significant association between the degree of polypharmacy and frailty score. The critical care pathway created extensive changes in patient medication therapy. Medication changes on care transitions often lacked detailed documentation.

The association of potentially inappropriate medications, polypharmacy and anticholinergic burden with readmission and emergency room revisit after discharge: A hospital-based retrospective cohort study.

AIMS: While certain drug-use indicators are known to be associated with clinical outcomes, the relationship is unclear for some highly prevalent conditions in in patients aged ≥65 years. We examine correlations between 3 drug-use indicators and postdischarge healthcare services use by older patients according to the presence of dementia, advanced age and frailty. METHODS: This retrospective cohort study analysed data collected from hospital electronic health records between April and December 2017. Potentially inappropriate medications (PIMs) and anticholinergic burden were assessed using the 2015 Beers Criteria and anticholinergic cognitive burden scale (ACBS) score. Minor and major polypharmacy were defined as the use of 5-9 and ≥10 drugs, respectively. Outcomes were set as emergency room revisits and readmissions at 1, 3 and 6 months postdischarge. The correlation between drug-use indicators and outcomes was analysed by multivariable logistic regression. RESULTS: The final cohort included 3061 patients for the analysis, and 2930, 2671 and 2560 patients were followed up to 1, 3 and 6 months after discharge. After controlling for confounders, all 3 drug-use indicators were significantly associated with readmission and emergency room revisits except for the relationship between PIMs and readmission within 6 months. These associations were significantly observed among patients without dementia, aged >80 years and with frailty. CONCLUSION: PIMs, polypharmacy and anticholinergic burden are common at discharge and correlate with future use of healthcare services. In older patients, the absence of dementia, advanced age and frailty should be given extra consideration with regard to medication safety.

Frailty as a predictor of delayed initiation of adjuvant chemotherapy in patients with ovarian cancer.

OBJECTIVE: This study aimed to identify whether frailty is associated with the time between surgery and the initiation of chemotherapy for patients with ovarian cancer. METHODS: This retrospective cohort study included patients 18 years or older with stage II to IV ovarian cancer who underwent primary debulking surgery at a tertiary medical center between July 2006 and July 2015. Basic demographics and clinical information were obtained from a departmental database and the electronic medical record. The Modified Frailty Index (mFI) was calculated based on 10 comorbidities and functional status yielding 11 items total. Patients were categorized by a total score: 0-1=no frailty, 2=moderate frailty and 3+=high frailty. RESULTS: Among 451 patients, 359 had mFI scores of 0-1, 60 had a score of 2, and 32 had scores of 3+. Mean time from surgery to initiation of chemotherapy was 37 days. Mean number of days between surgery and initiation of chemotherapy increased with increasing frailty score: 36 days for the not frail group, 39 days for the moderate frailty group, and 54 days for the high frailty group (p<0.001). Time to initiation of chemotherapy of 42 days or more occurred in 23% of the no frailty group, 28% in the moderate frailty group, and 63% in the high frailty group (p<0.001). Overall survival decreased with increasing frailty scores. CONCLUSION: High mFI scores lead to a greater delay between surgery and chemotherapy initiation. Being able to predict delays in initiation of chemotherapy may allow oncologists to consider neoadjuvant chemotherapy, pre-habilitation before surgery, and improved preoperative counseling in high-risk patients.

An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free survival (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up. Fit and <60 y patients were mostly treated with full intensity, whereas frail and ≥70 y patients usually received DR. Hematological and non-hematological SAE were more frequently seen in frail versus ≥70 y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (P=0.0245/P<0.0001), whereas in age-based subgroups, OS and PFS differences did not reach significance (P=0.1362/P=0.0569). Non-hematological SAE were another negative predictor for impaired OS and PFS (P=0.0054/P=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% versus deteriorated in only 10% of patients. In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.

[Assessment and treatment options for transplant-ineligible patients with multiple myeloma].

At diagnosis, approximately 40% of patients with multiple myeloma are older than 75 years. Thus, treatments for multiple myeloma should take into consideration the following factors: 1) disease-related factors, such as chromosomal abnormalities and speed of progression; 2) therapy-related factors, such as drug resistance and toxicity; and 3) patient-specific factors, such as age, organ dysfunction, and availability of family support. Moreover, with the development of novel therapeutic agents, including antibodies, overcoming the high risk of disease-related factors, even in older patients, is becoming possible by attaining favorable responses to treatment. However, the premise is to continue highly effective treatments from an early stage and maximize the performance of the selected treatments. Therefore, treatments must be provided regularly while adjusting its intensity and duration. Furthermore, for older patients with high frailty, improving and maintaining the health-related quality of life may be necessary. Hence, various treatments and frailty assessments here are described here, including therapeutic ingenuity and supportive care strategies for developing individualized treatments for transplant-ineligible patients.

Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia.

Sarcopenia refers to the age-related reduction in strength, muscle mass and functionality which increases the risk for falls, injuries and fractures. Sarcopenia is associated with other age-related conditions such as osteoporosis, frailty and cachexia. Identifying treatments to overcome sarcopenia and associated conditions is important from a global health perspective. There is evidence that creatine monohydrate supplementation, primarily when combined with resistance training, has favorable effects on indices of aging muscle and bone. These musculoskeletal benefits provide some rationale for creatine being a potential intervention for treating frailty and cachexia. The purposes of this narrative review are to update the collective body of research pertaining to the effects of creatine supplementation on indices of aging muscle and bone (including bone turnover markers) and present possible justification and rationale for its utilization in the treatment of frailty and cachexia in older adults.