Identifying barriers and tailoring interventions to improve the management of urinary tract infections and sore throat: a pragmatic study using qualitative methods

BACKGROUND: Theories of behaviour change indicate that an analysis of factors that facilitate or impede change is helpful when trying to influence professional practice. The aim of this study was to identify barriers to implementing evidence-based guidelines for urinary tract infection and sore throat in general practice in Norway, and to tailor interventions to address these barriers. METHODS: We used a checklist to identify barriers and possible interventions to address these in an iterative process that included a review of the literature, brainstorming, focus groups, a pilot study, small group discussions and interviews. RESULTS: We identified at least one barrier for each category. Both guidelines recommended increased use of telephone consultations and reduced use of laboratory tests, and the barriers and the interventions were similar for the two guidelines. The complexity of changing routines involving patients, general practitioners and general practitioner assistants, loss of income with telephone consultations, fear of overlooking serious disease, perceived patient expectations and lack of knowledge about the evidence for the guidelines were the most prominent barriers. The interventions that were tailored to address these barriers included support for change processes in the practices, increasing the fee for telephone consultations, patient information leaflets and computer-based decision support and reminders. CONCLUSION: A systematic approach using qualitative methods helped identify barriers and generate ideas for tailoring interventions to support the implementation of guidelines for the management of urinary tract infections and sore throat. Lack of resources limited our ability to address all of the barriers adequately

Targeting glucocorticoid receptors prevents the effects of early life stress on amyloid pathology and cognitive performance in APP/PS1 mice

Exposure to chronic stress or elevated glucocorticoid hormone levels in adult life has been associated with cognitive deficits and an increased risk for Alzheimer's disease (AD). Since exposure to stress during early life enhances stress-responsiveness and lastingly affects cognition in adult life, we here investigated; (i) whether chronic early life stress (ELS) affects AD pathology and cognition in middle-aged APPswe/PS1dE9 mice, and (ii) whether it is still possible to rescue these late effects by briefly blocking glucocorticoid receptors (GRs) at a translationally relevant, middle age. Transgenic APPswe/PS1dE9 mice were subjected to ELS by housing dams and pups with limited nesting and bedding material from postnatal days 2-9 only. In 6- and 12-month-old offspring, this resulted in enhanced hippocampal amyloid-β (Aβ)-40 and -42 levels, and in reduced cognitive flexibility, that correlated well with the Aβ42 levels. In parallel, CORT levels and BACE1 levels were significantly elevated. Surprisingly, blocking GRs for only 3 days at 12 months of age reduced CORT levels, reduced hippocampal Aβ40 and -42, and β-site APP-cleaving enzyme 1 (BACE1) levels, and notably rescued the cognitive deficits in 12-month-old APPswe/PS1dE9 mice. These mouse data demonstrate that exposure to stress during the sensitive period early in life influences later amyloid pathology and cognition in genetically predisposed, mutant mice, and as such, may increase AD vulnerability. The fact that a short treatment with a GR antagonist at middle age lastingly reduced Aβ levels and rescued the cognitive deficits after ELS, highlights the therapeutic potential of this drug for reducing amyloid pathology

Na⁺/K⁺-pump and neurotransmitter membrane receptors

Na+/K+-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na+/K+-ATPase pumps 3 sodium ions out of cells while pumping 2 potassium ions into cells. Both cations move against their concentration gradients. This enzyme’s electrogenic nature means that it has a chronic role in stabilizing the resting membrane potential of the cell, in regulating the cell volume and in the signal transduction of the cell. This review will mainly consider the role of the Na+/K+-pump in neurons, with an emphasis on its role in modulating neurotransmitter receptor. Most of the literature on the modulation of neurotransmitter receptors refers to the situation in the mammalian nervous system, but the position is likely to be similar in most, if not all, invertebrate nervous systems.</p