Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions

BACKGROUND: The aim of this study was to determine and compare patients' and physicians' perceptions of benefits and risks of long term benzodiazepine use for insomnia in the elderly. METHODS: A cross-sectional study (written survey) was conducted in an academic primary care group practice in Toronto, Canada. The participants were 93 patients over 60 years of age using a benzodiazepine for insomnia and 25 physicians comprising sleep specialists, family physicians, and family medicine residents. The main outcome measure was perception of benefit and risk scores calculated from the mean of responses (on a Likert scale of 1 to 5) to various items on the survey. RESULTS: The mean perception of benefit score was significantly higher in patients than physicians (3.85 vs. 2.84, p < 0.001, 95% CI 0.69, 1.32). The mean perception of risk score was significantly lower in patients than physicians (2.21 vs. 3.63, p < 0.001, 95% CI 1.07, 1.77). CONCLUSIONS: There is a significant discordance between older patients and their physicians regarding the perceptions of benefits and risks of using benzodiazepines for insomnia on a long term basis. The challenge is to openly discuss these perceptions in the context of the available evidence to make collaborative and informed decisions

Five mucosal transcripts of interest in ulcerative colitis identified by quantitative real-time PCR: a prospective study

<p>Abstract</p> <p>Background</p> <p>The cause and pathophysiology of ulcerative colitis are both mainly unknown. We have previously used whole-genome microarray technique on biopsies obtained from patients with ulcerative colitis to identifiy 5 changed mucosal transcripts. The aim of this study was to compare mucosal expressions of these five transcripts in ulcerative colitis patients vs. controls, along with the transcript expression in relation to the clinical ulcerative colitis status.</p> <p>Methods</p> <p>Colonic mucosal specimens from rectum and caecum were taken at ambulatory colonoscopy from ulcerative colitis patients (<it>n </it>= 49) with defined inflammatory activity and disease extension, and from controls (<it>n </it>= 67) without inflammatory bowel disease. The five mucosal transcripts aldolase B, elafin, MST-1, simNIPhom and SLC6A14 were analyzed using quantitative real-time PCR.</p> <p>Results</p> <p>Significant transcript differences in the rectal mucosa for all five transcripts were demonstrated in ulcerative colitis patients compared to controls. The grade of transcript expression was related to the clinical disease activity.</p> <p>Conclusion</p> <p>The five gene transcripts were changed in patients with ulcerative colitis, and were related to the disease activity. The known biological function of some of the transcripts may contribute to the inflammatory features and indicate a possible role of microbes in ulcerative colitis. The findings may also contribute to our pathophysiological understanding of ulcerative colitis.</p

Group 3 ITI Consensus Report: Patient-reported outcome measures associated with implant dentistry

Objectives: The aim of Working Group 3 was to focus on three topics that were assessed using patient-reported outcome measures (PROMs). These topics included the following: (a) the aesthetics of tooth and implant-supported fixed dental prostheses focusing on partially edentulous patients, (b) a comparison of fixed and removable implant-retained prostheses for edentulous populations, and (c) immediate versus early/conventional loading of immediately placed implants in partially edentate patients. PROMs include ratings of satisfaction and oral health-related quality of life (QHRQoL), as well as other indicators, that is, pain, general health-related quality of life (e.g., SF-36). Materials and methods: The Consensus Conference Group 3 participants discussed the findings of the three systematic review manuscripts. Following comprehensive discussions, participants developed consensus statements and recommendations that were then discussed in larger plenary sessions. Following this, any necessary modifications were made and approved. Results: Patients were very satisfied with the aesthetics of implant-supported fixed dental prostheses and the surrounding mucosa. Implant neck design, restorative material, or use of a provisional restoration did not influence patients’ ratings. Edentulous patients highly rate both removable and fixed implant-supported prostheses. However, they rate their ability to maintain their oral hygiene significantly higher with the removable prosthesis. Both immediate provisionalization and conventional loading receive positive patient-reported outcomes. Conclusions: Patient-reported outcome measures should be gathered in every clinical study in which the outcomes of oral rehabilitation with dental implants are investigated. PROMs, such as patients’ satisfaction and QHRQoL, should supplement other clinical parameters in our clinical definition of success

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers

Background: The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. Results: Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU’s). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilusspp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU’s residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). Conclusions: The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer “starts afresh” and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer

The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a ‘T7-like virus’ with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (104 and 106 pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy

Patient-reported outcome measures of the impact of cancer on patient’s everyday lives: a systematic review

Purpose: Patients with advanced disease are living longer and commonly used patient-reported outcome measures (PROMs) may miss relevant elements of the quality of extended survival. This systematic review examines the measures used to capture aspects of the quality of survival including impact on patients’ everyday lives such as finances, work and family roles. Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL and PsycINFO restricted to English language articles. Information on study characteristics, instruments and outcomes was systematically extracted and synthesised. A predefined set of criteria was used to rate the quality of studies. Results: From 2761 potentially relevant articles, 22 met all inclusion criteria, including 10 concerning financial distress, 3 on roles and responsibilities and 9 on multiple aspects of social well-being. Generally, studies were not of high quality; many lacked bias free participant selection, had confounding factors and had not accounted for all participants. High levels of financial distress were reported and were associated with multiple demographic factors such as age and income. There were few reports concerned with impacts on patients’ roles/responsibilities in everyday life although practical and emotional struggles with parenting were identified. Social difficulties were common and associated with multiple factors including being a caregiver. Many studies were single time-point surveys and used non-validated measures. Exceptions were employment of the COST and Social Difficulties Inventory (SDI), validated measures of financial and social distress respectively. Conclusions: Impact on some important parts of patients’ everyday lives is insufficiently and inconsistently captured. Further PROM development focussing on roles and responsibilities, including work and caring for dependents, is warranted. Implications for Cancer Survivors: Factors such as finances, employment and responsibility for caring for dependents (e.g. children and elderly relatives) can affect the well-being of cancer survivors. There is a need to ensure that any instruments used to assess patients’ social well-being are broad enough to include these areas so that any difficulties arising can be better understood and appropriately supported

Rationalising drug delivery using nanoparticles: a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles

Silica nanoparticles (SiNPs) have been shown to have significant potential for drug delivery and as adjuvants for vaccines. We have simulated the adsorption of GnRH-I (gonadotrophin releasing hormone I) and a cysteine-tagged modification (cys-GnRH-I) to model silica surfaces, as well as its conjugation to the widely-used carrier protein bovine serum albumin (BSA). Our subsequent immunological studies revealed no significant antibody production was caused by the peptide-SiNP systems, indicating that the treatment was not effective. However, the testosterone response with the native peptide-SiNPs indicated a drug effect not found with cys-GnRH-I-SiNPs; this behaviour is explained by the specific orientation of the peptides at the silica surface found in the simulations. With the BSA systems, we found significant testosterone reduction, particularly for the BSA-native conjugates, and an antibody response that was notably higher with the SiNPs acting as an adjuvant; this behaviour again correlates well with the epitope presentation predicted by the simulations. The range of immunological and hormone response can therefore be interpreted and understood by the simulation results and the presentation of the peptides to solution, paving the way for the future rational design of drug delivery and vaccine systems guided by biomolecular simulation

Role of X11 and ubiquilin as In Vivo Regulators of the Amyloid Precursor Protein in Drosophila

The Amyloid Precursor Protein (APP) undergoes sequential proteolytic cleavages through the action of β- and γ-secretase, which result in the generation of toxic β-amyloid (Aβ) peptides and a C-terminal fragment consisting of the intracellular domain of APP (AICD). Mutations leading to increased APP levels or alterations in APP cleavage cause familial Alzheimer's disease (AD). Thus, identification of factors that regulate APP steady state levels and/or APP cleavage by γ-secretase is likely to provide insight into AD pathogenesis. Here, using transgenic flies that act as reporters for endogenous γ-secretase activity and/or APP levels (GAMAREP), and for the APP intracellular domain (AICDREP), we identified mutations in X11L and ubiquilin (ubqn) as genetic modifiers of APP. Human homologs of both X11L (X11/Mint) and Ubqn (UBQLN1) have been implicated in AD pathogenesis. In contrast to previous reports, we show that overexpression of X11L or human X11 does not alter γ-secretase cleavage of APP or Notch, another γ-secretase substrate. Instead, expression of either X11L or human X11 regulates APP at the level of the AICD, and this activity requires the phosphotyrosine binding (PTB) domain of X11. In contrast, Ubqn regulates the levels of APP: loss of ubqn function leads to a decrease in the steady state levels of APP, while increased ubqn expression results in an increase in APP levels. Ubqn physically binds to APP, an interaction that depends on its ubiquitin-associated (UBA) domain, suggesting that direct physical interactions may underlie Ubqn-dependent regulation of APP. Together, our studies identify X11L and Ubqn as in vivo regulators of APP. Since increased expression of X11 attenuates Aβ production and/or secretion in APP transgenic mice, but does not act on γ-secretase directly, X11 may represent an attractive therapeutic target for AD