Effects of low dose morphine on perceived sleep quality in patients with refractory breathlessness : a hypothesis generating study

© 2015 Asian Pacific Society of Respirology. Background and objective The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. Methods This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. Results Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). Conclusion Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality

Cost-effectiveness and value of information analysis of NephroCheck and NGAL tests compared to standard care for the diagnosis of acute kidney injury

Acknowledgements We are grateful to Thomas Walker and Rebecca Albrow at NICE for their thoughtful comments on earlier versions of the economic model and to the NICE Diagnostic Committee for their critical review of our identifed evidence. We are also grateful for the advice and clinical guidance received from the NICE Specialist Advisory Group for DG19 and to Peter S Hall and Alison F Smith (on behalf of the team) for providing early versions of their economic model that was instrumental in the development and structuring of the model used in this study. A big thank goes also to Lara Kemp for her secretarial support and patience throughout the study. The results presented in this paper have not been published previously in any academic journals, nor have they been submitted elsewhere. This work has informed the development of NICE guidance for diagnostic testing for AKI (https://www.nice.org.uk/guidance/dg39) and a full report to the funder describing the totality of this work will be published in the NIHR, HTA mono‑ graph series in due course. Funding The fndings presented in this manuscript are part of a broader research project funded by the National Institute for Health Research (NIHR) and com‑missioned through the NICE Diagnostic Assessment Programme (project no 12/88/97). The views expressed are those of the authors and not necessarily those of NICE, the NHS, the NIHR or the Department of Health. The Health Economics Research Unit and the Health Services Research Unit, University of Aberdeen, are funded by the Chief Scientist Ofce of the Scottish Government Health and Social Care Directorates.Peer reviewedPublisher PD

Prescription opioid use disorder and heroin use among 12-34 year-olds in the United States from 2002 to 2014

Trend analyses of prescription opioids in the U.S. indicate use, especially use of prescription opioids stronger than morphine, has more than doubled among adults since the early 1990's (Frenk, Porter, & Paulozzi, 2015). Prescription opioids, like Oxycontin®, are effective pharmacological treatments for acute and chronic pain (Fitzcharles and Shir, 2009 ; Gallagher and Rosenthal, 2008). When used as indicated, these medications can be an important component of pain management. However, their high abuse potential presents concerns regarding their nonmedical use, which can be defined as ‘use of a prescription opioid that was not prescribed, or taken for the experience or feeling it caused’ (SAMHSA, 2014). In the United States, nonmedical use of prescription opioids (NMPO) is increasingly recognized as a serious public health problem among adults (Blanco et al., 2007; Han et al., 2015 ; Huang et al., 2006). Nonmedical prescription drug use, specifically nonmedical use of prescription opioids, is also a growing problem in other countries such as Canada (Fischer et al., 2014 ; Fischer et al., 2013) and Australia (Degenhardt et al., 2006 ; Rintoul et al., 2011)

Sensitive and specific serodiagnosis of Leishmania infantum infection in dogs by using peptides selected from hypothetical proteins identified by an immunoproteomic approach

In Brazil, the percentage of infected dogs living in areas where canine visceral leishmaniasis (CVL) is endemic ranges from 10 to 62%; however, the prevalence of infection in dogs is probably higher than figures reported from serological studies. In addition, problems with the occurrence of false-positive or false-negative results in the serodiagnosis of CVL have been reported. The present work analyzed the potential of synthetic peptides mapped from hypothetical proteins for improvement of the serodiagnosis of Leishmania infantum infection in dogs. From 26 identified leishmanial proteins, eight were selected, considering that no homologies between these proteins and others from trypanosomatide sequence databases were encountered. The sequences of these proteins were mapped to identify linear B-cell epitopes, and 17 peptides were synthesized and tested in enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of L. infantum infection in dogs. Of these, three exhibited sensitivity and specificity values higher than 75% and 90%, respectively, to differentiate L. infantum-infected animals from Trypanosoma cruziinfected animals and healthy animals. Soluble Leishmania antigen (SLA) showed poor sensitivity (4%) and specificity (36%) to differentiate L. infantum-infected dogs from healthy and T. cruzi-infected dogs. Lastly, the three selected peptides were combined in different mixtures and higher sensitivity and specificity values were obtained, even when sera from T. cruzi-infected dogs were used. The study’s findings suggest that these three peptides can constitute a potential tool for more sensitive and specific serodiagnosis of L. infantum infection in dogsThis work was supported by grants from the Pró-Reitoria de Pesquisa from UFMG (Edital 07/2012), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-NANOBIOFAR, Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (CBB-APQ-02364-08, CBB-APQ-00356-10, CBB-APQ-00496-11, and CBB-APQ-00819-12), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (APQ-472090/2011-9), and the Instituto Nacional de Ciência e Tecnologia em Vacinas (INCT-V). E.A.F.C. and A.P.F. are CNPq grant recipients. M.A.C.-F. is a FAPEMIG/CAPES grant recipient. This study was supported in Spain, in part, by grants from the Ministerio de Ciencia e Innovación (FIS/PI1100095)

Adverse cardiovascular events and mortality in men during testosterone treatment : an individual patient and aggregate data meta-analysis

Funding National Institute for Health Research Health Technology Assessment Programme. Acknowledgments This work was supported by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project no 17/68/01). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR HTA Programme, or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit for publication were performed independent of the funders. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. The following authors are also funded as follows: NIHR Research Professorship (WSD), NIHR post-doctoral fellowship (CNJ). SBhasin receives National Institutes of Health research grant funding. The authors are grateful to Prakash Abraham, Alison Avenell, Craig Ramsay, Graham Scotland, Neil Scott, and Finlay MacKenzie for their advice; and to the many individuals from academia and industry who helped in the conduct of this study.Peer reviewedPublisher PD

Functional and Transcriptional Induction of Aquaporin-1 Gene by Hypoxia; Analysis of Promoter and Role of Hif-1α

Aquaporin-1 (AQP1) is a water channel that is highly expressed in tissues with rapid O2 transport. It has been reported that this protein contributes to gas permeation (CO2, NO and O2) through the plasma membrane. We show that hypoxia increases Aqp1 mRNA and protein levels in tissues, namely mouse brain and lung, and in cultured cells, the 9L glioma cell line. Stopped-flow light-scattering experiments confirmed an increase in the water permeability of 9L cells exposed to hypoxia, supporting the view that hypoxic Aqp1 up-regulation has a functional role. To investigate the molecular mechanisms underlying this regulatory process, transcriptional regulation was studied by transient transfections of mouse endothelial cells with a 1297 bp 5′ proximal Aqp1 promoter-luciferase construct. Incubation in hypoxia produced a dose- and time-dependent induction of luciferase activity that was also obtained after treatments with hypoxia mimetics (DMOG and CoCl2) and by overexpressing stabilized mutated forms of HIF-1α. Single mutations or full deletions of the three putative HIF binding domains present in the Aqp1 promoter partially reduced its responsiveness to hypoxia, and transfection with Hif-1α siRNA decreased the in vitro hypoxia induction of Aqp1 mRNA and protein levels. Our results indicate that HIF-1α participates in the hypoxic induction of AQP1. However, we also demonstrate that the activation of Aqp1 promoter by hypoxia is complex and multifactorial and suggest that besides HIF-1α other transcription factors might contribute to this regulatory process. These data provide a conceptual framework to support future research on the involvement of AQP1 in a range of pathophysiological conditions, including edema, tumor growth, and respiratory diseases

Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy

Mulheres idosas: desvelando suas vivências e necessidades de cuidado

Estudo qualitativo com abordagem da fenomenologia social que objetivou a compreensão da vivência da mulher idosa, suas necessidades de cuidado e expectativas nesse período da vida. Participaram nove mulheres, cujos depoimentos foram obtidos de fevereiro a maio de 2011, por meio de entrevista semiestruturada. A mulher idosa refere limitações de ordem física, mental e social, e valoriza a preservação de sua autonomia nas atividades diárias e no cuidado consigo mesma. Refere a família como suporte fundamental e tem expectativas e necessidades de se manter saudável, da busca pelo lazer e de ter melhor acesso aos serviços de saúde para receber informações e atendimento qualificado. Nessa fase, a ausência de perspectivas relaciona-se à perda de pessoas significativas e da saúde. Este estudo revelou facetas da vivência da mulher idosa, suscitando novas investigações e a adequação do ensino, prática e gestão às reais necessidades dessa mulher