181 research outputs found
Comparative efficacy and acceptability of pharmacological treatments for insomnia in adults: a systematic review and network meta-analysis
No full textThis is the protocol for a review and there is no abstract. The objectives are as follows: 1) To compare individual pharmacological treatments for insomnia in adults in terms of: efficacy, measured as self-rated quality of sleep or satisfaction with sleep; and acceptability of treatment. 2) To generate a clinically-useful hierarchy of available pharmacological treatments for insomnia in adults, according to their efficacy and acceptability
Serotonin receptor mechanisms in anti-depressant action
No full textBibliography: leaves 221-270.Serotonin neurones have been implicated in the pathophysiology and treatment of clinical depression to a greater degree than any other neurotransmitter. Additionally, serotonin pathways may playa role in the pathophysiology and treatment of eating disorders, anxiety states and schizophrenia. Molecular biological studies have confirmed pharmacological evidence suggesting the existence of multiple serotonin receptor subtypes and the genes for these receptors, as well as that of the serotonin transporter, have common polymorphic variants. To investigate the effect of repeated treatment with selective serotonin fe-uptake inhibitors (SSRI's) on the function of central 5-HT2C receptors. To assess the effect of polymorphic variation in the 5-HT2c receptor and serotonin transporter on functional responses to selective pharmacological challenge. To determine whether polymorphic variation in the 5-HT receptor and serotonin transporter influence the clinical response of patients with major depression to treatment with serotonergic antidepressants. To assess the effect of repeated treatment with selective serotonin re-uptake inhibitors (SSRI's) on the function of central 5-HT2c receptors I used the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP) as a 5-HT2c probe in a neuroendocrine challenge paradigm. I used the same approach to assess whether polymorphic variation in the 5-HT2c receptor (serine vs cysteine substitution) was associated with differences in functional response to 5-HT2C receptor challenge. I then studied whether polymorphic variation in the serotonin transporter promotor region (long versus short form) was associated with differing functional responses to acute challenge with clomipramine, a tricyclic antidepressant with a high affinity for the serotonin transporter. Finally, I studied whether either of these polymorphic variants influenced the clinical response of patients with major depression to treatment with SSRI's and clomipramine. SSRI treatment significantly lowered the sensitivity of 5-HT2c receptors as predicted from animal experimental studies. However polymorphic variation in the 5-HTzc receptor did not significantly influence functional responses to m-CPP challenge. In contrast polymorphic variation in the serotonin transporter was associated with differing neuroendocrine responses to acute clomipramine challenge with greater prolactin release being seen in subjects with the long polymorphic variant. Neither the 5-HTzc nor the transporter polymorphisms correlated with clinical response to SSRI and clomipramine treatment in patients with major depression. The ability of SSRI's to produce a functional down-regulation of 5-HTzc receptors may be relevant to certain of their therapeutic effects. Polymorphic variation in the 5-HT2c receptor (serine vs cysteine) seems unlikely to explain functional differences in responses to 5-HTzc receptor challenge or antidepressant responses to SSRI treatment. In contrast variation in the serotonin transporter promotor is associated with differing functional responses to acute serotonin re-uptake blockade. However, this did not correlate with clinical response to longer-term SSRI treatment
Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
No full textBACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre
La Vie de un vallet amerous (Digby 86): a dramatic monologue on the practice and pitfalls of seduction in medieval Britain – by Richard, author of the Besturné?
No full textSurviving in a single copy in Oxford, Bodleian Library, MS Digby 86, the poem La Vie de un vallet amerous has garnered itself a reputation for its singular obscenity, but it is arguably of greater interest in Anglo-Norman literary history for being a comic dramatic monologue composed in a distinctive verse form. The present article offers a new critical edition of the text and reflects on its relationship to the rest of the manuscript, with particular attention to its affinities to La Besturné, an Anglo-Norman nonsense poem conventionally attributed to a certain Richard
Growing Old in Oxford 1930-1960
No full textThis thesis explores how old people in Oxford were cared for between 1930 and 1960, before and after the inception of the welfare state. Its purpose is to analyse how some families and professionals responded to the transition from the poor law to the welfare state, and examine any changes in this process. Admission to a state institution was usual for old people who were without financial and social resources. In Oxford the Cowley Road Hospital, originally built as a workhouse in the nineteenth century provided this treatment over this period of time.
The thesis investigates the relationship of this institution to the broader community in relation to the care of old people. From the 1930s geriatric medicine, a speciality emerged spearheaded by Dr Marjory Warren, geriatric medicine. Early pioneers of geriatric medicine, working in state run institutions, were advocating the need for change in provision for old people, and this study examines their role in this process of change. Within this group of doctors, Dr Lionel Cosin, an initiator and influencer of change and policy in post-war care for old people, was appointed to the Cowley Road Hospital soon after the inception of the welfare state. This thesis seeks to discover in conjunction with the changes arising from the introduction of the welfare state, if old people in Oxford benefitted from his position.
By using oral histories as a major source of evidence, alongside documentary sources, this investigation aims to bring fresh perspectives to the study of the process of ageing. Within the context of national legislative changes it discovers how a city responded to these, and juxtaposes how families cared for their older relatives. Each chapter examines aspects that contributed to changing provision and attitudes towards old people by professionals and relatives. Local evidence is compared with national to suggest that the city was progressive in its care and attitudes towards old people
'Where of is mad al mankynde' : an edition of and introduction to the twenty-four poems in Oxford, Bodleian Library, MS Digby 102
No full text'Where of is Mad al Mankynde' represents a new critical edition of the collection of twenty-four late-medieval anonymous poems contained, among other pieces, in Oxford, Bodleian Library, MS Digby 102. Each poem is introduced with a brief summary and closes with line-for-line explanatory comments. The poems are glossed both in the margin and in footnotes. The text edition is preceded by codicological and linguistic analyses, including a discussion of dialect and dating, and by a survey of the literary and cultural background, including a discussion of the identity of the author and his audience. The text edition is followed by a comprehensive glossary, an index of names, authors and subjects, and a bibliography.LEI Universiteit LeidenMedieval and Early Modern Studie
The MS Digby 133 Mary Magdalene. Beyond scribal practices: language, discourse, values and attitudes
No full textThe MS133 Digby Mary Magdalene has commonly been investigated by paying attention to literary features, while linguistic aspects have seldom been taken into consideration, with the result that any deviation from the norm has been classified as scribal inconsistency. On the contrary, what has been regarded as scribal carelessness actually seems to be a modern misunderstanding of scribal practices. Indeed, the significant combination of Southern, Midlands and Northern elements featuring the language of Mary Magdalene is the result of the scribe’s desire to faithfully reproduce the author’s design, in which variants may have a marked social function. We can thus infer that the Mary Magdalene author probably created a sort of biblical koiné, shared with the audience, which was realized with the linguistic varieties offered by the existing late Middle English dialects and clearly exploited not only for poetic but also, and above all, for religious purposes. At the same time, the text puts an innovative emphasis on the figure of Mary Magdalene, who simultaneously plays the role of sinner and saint, virgin and prostitute, female and male. Thanks to the methodological approach employed, this volume shows that most unusual forms are diatopic and diastratic alternatives used in specific religious contexts to realize well-defined sociolinguistic purposes
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Supporting Latino Students with Interrupted Formal Education: A Guide for Teachers
No full textThis professional development guide supports K-12 teachers to approach their incoming students from other countries who stopped attending school and now face the double challenge to go back to their studies and under a new education system. The author wrote the guide based on her experience in Honduras, but also drew from her expertise in teaching in New York City
A letter of advice to all the worthy and ingenuous merchants of the city of London, [electronic resource] : and elsewhere in England, Scotland, and Ireland; And also to all the Worthy and Ingenuous Merchants of France, and of Holland and the United-Provinces, and of Germany, Spain, Portugal, Denmark, and Sweden, and elsewhere in Europe; and To all Ingenuous and Ingenious Artists in Astronomy, Geography, and Navigation; shewing An exact, easie and speedy Way to know the Longitude of all Places in the World, where the European Merchants have their Agents to make Observations; and also How the Longitude of Places may be better known upon Ship-Board. Written by Digby Bull, M. A. and late Rector of Sheldon in Warwick-Shire.
No full textElectronic reproduction.English Short Title Catalog,Reproduction of original from British Library
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