U-CHANGE Project: a multidimensional consensus on how clinicians, patients and caregivers may approach together the new urothelial cancer scenario.

Introduction: Advanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations ("as is" scenario) and recommend future actions ("to be" scenario). Methods: Twenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts. Results: Recommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies. Discussion: While the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease.

Counting deficits or diseases? The agreement between frailty and multimorbidity in subjects with cognitive disturbances.

In the present study, we explored the relationship between multimorbidity and frailty in a population of older individuals with cognitive disturbances attending a memory clinic. All subjects consecutively attending the Memory Clinic of the Department of Human Neuroscience, "Sapienza" University of Rome, between January 2017 and April 2018 for a first neurological evaluation were considered for the present analysis. Multimorbidity was defined as the simultaneous presence of two or more diseases in the same individual. A Frailty Index was computed by considering 44 age-related, multidimensional health deficits. Overall, 185 subjects were recruited in the study. A condition of multimorbidity was detected in 87.6% of the sample, whereas only the 44.6% of the study population was considered as frail. A poor agreement was observed between multimorbidity and frailty. The present findings confirm that counting diseases or health deficits may provide discordant information concerning the risk profile of older subjects.

Race reporting and disparities in clinical trials on Alzheimer's disease: A systematic review.

INTRODUCTION: Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD). METHODS: A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications. RESULTS: Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants. DISCUSSION: Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected.

Spontaneous Reversion of Clinical Conditions Measuring the Risk Profile of the Individual: From Frailty to Mild Cognitive Impairment.

The number of people living with disabilities worldwide is rapidly growing due to a longer life expectancy and the subsequent increasing burden of chronic diseases. The need of developing and implementing effective strategies aimed at delaying or preventing disability has been repeatedly underlined and is currently the main focus of several health-care policies. In this scenario, a special attention is addressed to the identification of specific clinical conditions measuring the risk profile of the individual of developing an overt disability and other negative outcomes. These risk profiles can indeed become promising targets for developing and implementing preventive interventions. When the disabling cascade is fully established, in fact, the reversing/attenuating the process becomes more challenging. However, the exact nature of these relatively new constructs is not yet sufficiently clear, and several related issues remain poorly explored. In particular, these entities tend to be considered as unequivocally prodromal stages of a future disease, neglecting and underestimating their fluctuations/transitions over time and their potential to clinically improve/revert. This unbalanced judgment did probably contribute to an ambiguous and biased use of these conditions. Considering them as an early stage of an unavoidable future disease, in fact, determined a tendency to start a targeted intervention as if in presence of the disease itself, with the subsequent risk of over-diagnosis and over-treatment. In the present article, we discuss the dynamics underlying the reversion from a clinical at-risk condition to normality and its implications, specifically focusing on the examples of frailty and mild cognitive impairment.

Sex and gender differences in the treatment of Alzheimer's disease: A systematic review of randomized controlled trials.

In recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influence of sex and gender on Alzheimer's disease (AD). Nevertheless, not enough attention has been paid to their impact on treatment outcomes. The present study is aimed at systematically retrieve, review and discuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketed treatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possible sex and gender differences in their efficacy, safety and tolerability. A systematic review of literature was performed. None of the retrieved studies reported data on the efficacy, safety and tolerability of considered medications separately in male and female patients with AD. We thus analyzed 48 excluded studies of potential interest, that is, almost all of the currently available trials on the four considered drugs. Nearly all the considered RCTs recruited a larger number of female participants to mirror the sexually unbalanced prevalence of AD. Only two studies took into account the potential influence of sex and gender on treatment efficacy, reporting no significant differences between men and women. None of the studies investigated potential sex and gender differences in the safety and tolerability of the four considered treatments. The existence of sex and gender differences in the efficacy and tolerability of ChEIs and memantine in AD has, to date, drawn limited to no attention. However, a considerable amount of data, with an adequate representativeness in terms of sex/gender distribution, seem to be already available for dedicated analyses on this topic. A greater effort should be made to collect and report data on those factors interacting with sex and gender that may significantly influence clinical manifestations, outcomes, and trajectories over time of AD patients.