Springer Science and Business Media LLC

The introduction of targeted therapies has radically changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, multiple clinical dilemmas have emerged. For instance, limited data are available to juxtapose the safety and efficacy profile of targeted therapies between older and younger adults. Herein, pivotal trials of vascular endothelial growth factor (VEGF)- and mammalian target of rapamycin (mTOR)-directed therapies are assessed in the context of their implications in treating older adults with mRCC. In general, subset analyses from these pivotal studies suggest similar efficacy of targeted therapies amongst older adults. Aging is accompanied by a multitude of physiological changes, as well as an increased prevalence of co-morbidities. The age-related toxicity profiles of targeted agents for mRCC are detailed to provide a framework for the risks and benefits of these therapies in older adults. Ultimately, tools such as the Comprehensive Geriatric Assessment (CGA) that account for physiological (as opposed to chronological) age may prove useful in the evaluation and treatment of older adults with mRCC.

Several recent in vitro investigations and experimental studies performed in animal models of osteoarthritis (OA) sustained the previously held view that interleukin (IL)-1 or tumour necrosis factor-α (TNFα) disrupt the metabolism of synovial joint tissues. The evidence to date indicates that, in addition to IL-1 and TNFα, other pro-inflammatory cytokines, including IL-6, members of the IL-6 protein superfamily, IL-7, IL-17 and IL-18, can also promote articular cartilage extracellular matrix protein degradation or synergize with other cytokines to amplify and accelerate cartilage destruction. Most importantly, many of these cytokines have been implicated in causing synovial tissue activation and damage to subchondral bone as well as altering cartilage homeostasis in spontaneously occurring or surgically induced animal models of OA and in transgenic mice genetically primed to develop OA. In this regard, these pro-inflammatory cytokines may also play a significant role in the pathogenesis of human OA. However, attempts to modify the progression of human OA in well designed, controlled clinical trials with an IL-1 receptor antagonist protein (IRAP) have not been successful. Several anabolic cytokines (also termed growth factors), including transforming growth factor-β (TGF-β), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF) and connective tissue growth factor (CTGF), have also been proposed as regulators of skeletal long bone growth and development as well as cartilage and bone homeostasis. TGF-β, IGF-1 and FGF-2, in particular, have been characterized as potential chondroprotective agents. Thus, enzymatic disruption and removal of these growth factors from cartilage extracellular matrix proteins, as in the case of TGF-β and FGF-2, or disruption of their function, as in the case of the enhanced binding of free IGF-1 with IGF binding proteins in OA joint synovial fluid, may compromise and ultimately be responsible for the inadequate repair of articular cartilage in OA. An improved understanding of the cellular and molecular mechanisms by which pro-inflammatory and/or anabolic cytokines alter both the structure and function of synovial joints may eventually result in the commercial development of disease-modifying OA drugs (DMOADs). Since the prevalence of OA is high in the elderly population, future development of DMOADs must also take into account potential differences in the way DMOADs would be metabolized in the older individual compared with younger people.

Spondylarthritis (SpA) is generally observed in young male patients but can be diagnosed in older patients. These cases correspond to late-onset SpA (LoSpA) with two main clinical presentations, axial and peripheral SpA. Another increasingly common situation is that of older patients who have had SpA for many years. The therapeutic management of LoSpA is quite smilar to the management of patients with an early-onset disease, combining both non-pharmacological and pharmacological treatments. The treatments that can be used in LoSpA include non-steroidal anti-inflammatory drugs (NSAIDs) and biological agents targeting TNFα or IL-17A. Janus kinase inhibitors (JAKi) were recently introduced on the market for SpA. TNF inhibitors and IL-17inhibitors are very effective drugs in early-onset SpA. The effectiveness and safety of targeted therapies have not been specifically evaluated in LoSpA or older patients, and thus caution is required for these patients with comorbidities and/or polymedication. According to indirect data, biological agents seem to be less effective in LoSpA compared with early-onset disease. In parallel, a careful evaluation for the risk of infection, malignancy and cardiovascular events is recommended before initiating these drugs in this age category. JAKi may be used in LoSpA, but only in selected patients according to recent recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). When considering that the prevalence of such situations is expected to increase as ageing progresses, it is certainly time to consider this patient category as a distinct subgroup within the spectrum of SpA. Specific studies evaluating targeted agents in this age category are thus desirable.

Inappropriate polypharmacy may negatively impact the quality of life of residents in aged care facilities, but it remains unclear which medications may influence this reduced quality of life. The objective of this study was to examine whether the Drug Burden Index and potentially inappropriate medications were associated with quality of life in older adults living in residential care with a high prevalence of cognitive impairment and dementia. We conducted cross-sectional analyses of 541 individuals recruited from 17 residential aged care facilities in Australia in the Investigating Services Provided in the Residential Environment for Dementia (INSPIRED) study. Quality of life was measured using the EuroQol Five Dimensions Questionnaire (a measure of generic quality of life) and the Dementia Quality of Life Questionnaire completed by the participant or a proxy. In the 100 days prior to recruitment, 83.1% of the participants received at least one anticholinergic or sedative medication included in the Drug Burden Index and 73.0% received at least one potentially inappropriate medication according to the Beers Criteria. Multi-level linear models showed there was a significant association between a higher Drug Burden Index and lower quality of life according to the EuroQol Five Dimensions Questionnaire [β (standard error): − 0.034 (0.012), p = 0.006] after adjustment for potential confounding factors. Increasing numbers of potentially inappropriate medications were also associated with lower EuroQol Five Dimensions Questionnaire scores [− 0.030 (0.010), p = 0.003] and Dementia Quality of Life Questionnaire-Self-Report-Utility scores [− 0.020 (0.009), p = 0.029]. Exposure to both Drug Burden Index-associated medications and potentially inappropriate medications was associated with lower Dementia Quality of Life Questionnaire-Self-Report-Utility scores [− 0.034 (0.017), p = 0.049]. Exposure to anticholinergic and sedative medications and potentially inappropriate medications occurred in over three-quarters of a population of older adults in residential care and was associated with a lower quality of life.

The aim of the present study was to investigate how potentially inappropriate medication usage and anti-dementia drug use change from 3 years prior to, up until 3 years post-diagnosis of major neurocognitive disorders among older people living in Sweden. People registered in the Swedish registry for cognitive/dementia disorders from 1 July, 2008 to 31 December, 2017, and aged 68 years or older at diagnosis, were included (n = 67,226). Data were combined with the Swedish Prescribed Drug Registry to obtain information about drugs collected in 6-month periods at Swedish pharmacies from 3 years pre-diagnosis until 3 years post-diagnosis. Potentially inappropriate medications were identified according to Swedish national guidelines. A generalised estimating equation regression model and estimated marginal means were used. Of the 67,226 people included in the study population, 59.2% were women and the mean age ± standard deviation was 81.5 ± 6.4 years, 47.0% lived together with a spouse or partner, and 88.9% were living at home at the time of diagnosis. The proportions of people using potentially inappropriate medications continuously decreased pre- and post-diagnosis, except for antipsychotic drug use, which continuously increased both pre- and post-diagnosis. Moreover, anticholinergic drug use increased pre-diagnosis and declined post-diagnosis. When comparing the periods pre- and post-diagnosis date, the adjusted proportion of people using potentially inappropriate medications was significantly lower post-diagnosis compared with pre-diagnosis, except for the adjusted proportion using antipsychotics, which was significantly higher post-diagnosis, 10.6%, compared with the period before, 3.1% (adjusted odds ratio 3.71; 95% confidence interval 3.59–3.83). The adjusted proportion of people using anticholinergic drugs was significantly lower post-diagnosis, 7.2%, compared with the pre-diagnosis period, 8.9% (adjusted odds ratio 0.80; 95% confidence interval 0.78–0.82). Anti-dementia drug use was significantly higher post-diagnosis, 52.6%, when compared with the pre-diagnosis period, 3.5% (adjusted odds ratio 30.13; 95% confidence interval 29.19–31.10). Overall, the prevalence of people using potentially inappropriate medications decreased and was significantly lower post-diagnosis of major neurocognitive disorders, except for antipsychotics. This indicates that potentially inappropriate medication use should be noticed and reviewed among all older people. The small decrease in the prevalence of anticholinergic drug users and the increasing proportions of people using antipsychotic drugs post-diagnosis are of special concern because of the adverse drug reactions associated with these types of potentially inappropriate medications. Consequently, it is important to identify and regularly question anticholinergic and antipsychotic drug treatment to prevent unnecessary and serious adverse drug reactions among a vulnerable group of people.

The present trial was originally designed to investigate the effectiveness of comprehensive day hospital care in chronically ill elderly patients. Another aim, reported here, was to investigate to what extent it is possible to reduce polypharmacy and simplify drug regimens during the short term tight control conditions of day hospital care. All home care patients (n = 174, mean age 77 years) in a rural area, Kirkkonummi-Siuntio, in Finland. Patients were randomised into 2 groups, one of which was offered a 2-month period of day hospital care. Patients assumed to be noncompliant (because they did not want day hospital care) were also included in order to see the effect of intervention in ‘real-life’. The medications of all participants were reviewed and counted during an in-home assessment by a home nurse. In the intervention group, necessary revisions (dose reduction, discontinuation, possible additions) were performed through the tight monitoring of day hospital care and in co-operation with the patient. The patients were followed up for 10 months after completion of the intervention programme. Number of prescribed medications, number of over-the-counter (OTC) drugs, number of doses taken daily by the patients. Assessments were performed at baseline, and after 2, 5 and 12 months. There were no significant changes in the number of prescribed medications. In patients in day hospital care, the number of doses was reduced significantly (p = 0.02) during the 2-month day hospital period compared with the control group. However, the patients compensated for the reductions by increasing the use of OTC drugs during the day hospital period (p = 0.05). In addition, only 3 months after the trial, the number of drugs had already returned to the baseline level. In real life it seems to be difficult to reduce polypharmacy in the elderly. Some drug reductions may be achieved with tight control under trial conditions, but when the intervention ceases the number of drugs used soon returns to its earlier level.

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32–1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78–1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.