Purpose: Benzodiazepines are effective medicines for insomnia and anxiety but are commonly used beyond recommended treatment time frames, which may lead to adverse drug events. The aimof this systematic review was to critically evaluate the success of interventions used to reduce benzodiazepines and ‘Z-drug’ use, and the impact of these interventions on clinical outcomes in older adults. Methods: A search was conducted in PubMed, Embase, Informit, International Pharmaceutical Abstracts, Scopus, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL. Studies conducted in older adults (≥65 years) and published between January 1995 and July 2015 were included. Two authors independently reviewed all articles for eligibility and extracted the data. Results: Seven studies of benzodiazepines and Z-drug withdrawal were identified. Benzodiazepine discontinuation rates were 64.3% in one study that employed pharmacological substitution with melatonin and 65.0% in a study that employed general practitioner-targeted intervention. Mixed interventions including patient education and tapering (n = 2), pharmacological substitution with psychological support (n = 1) and tapering with psychological support (n = 1) yielded discontinuation rates between 27.0 and 80.0%. Five studies measured clinical outcomes following benzodiazepine discontinuation. Most (n = 4) observed no difference in prevalence of withdrawal symptoms or sleep quality, while one study reported decline in quality of life in those who continued taking benzodiazepine vs. those who discontinued over 8 months. Conclusions: Current evidence shows that benzodiazepine withdrawal is feasible in the older population, but withdrawal rates vary according to the type of intervention. As the benefits and sustainability of these interventions are unclear, further studies should be conducted to assess this

Our results suggest that compared to final pathology, biopsy of small renal masses accurately informs an algorithm incorporating size and histological risk group that directs the management of small renal masses.

Naïve T cell responses are eroded with aging. We and others have recently shown that unimmunized old mice lose ≥70% of Ag-specific CD8 T cell precursors and that many of the remaining precursors acquire a “virtual (central) memory” (VM; CD44hiCD62Lhi) phenotype. Here, we demonstrate that unimmunized T cell receptor (TCR) transgenic (Tg) mice also undergo massive VM conversion with age, exhibiting rapid effector function upon both TCR and cytokine triggering. Age-related VM conversion in TCRTg mice directly depended upon replacement of the original TCRTg specificity by endogenous TCRα rearrangements, indicating that TCR signals must be critical in VM conversion. Importantly, we found that VM conversion had adverse functional effects in both old wild type and old TCRTg mice - old VM, but not old true naïve, T cells exhibited blunted TCR-mediated, but not IL-15-mediated, proliferation. This selective proliferative senescence correlated with increased apoptosis in old VM cells in response to peptide, but decreased apoptosis in response to homeostatic cytokines IL-7 & IL-15. Our results identify TCR as the key factor in differential maintenance and function of Ag-specific precursors in unimmunized mice with aging, and demonstrate that two separate age-related defects – drastic reduction in true naïve T cell precursors and impaired proliferative capacity of their VM cousins –combine to reduce naïve T cell responses with aging.

Xp11.2 translocation-associated RCC represents a predominant and aggressive subtype in the paediatric age group. Increased awareness of this subtype is important due to its heterogeneous morphology.