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Adults with attention deficit hyperactivity disorder (ADHD) frequently suffer from sleep problems and report high levels of daytime sleepiness compared to neurotypical controls, which has detrimental effect on quality of life.
We evaluated daytime sleepiness in adults with ADHD compared to neurotypical controls using an observer-rated sleepiness protocol during the Sustained Attention Response Task as well as electroencephalogram (EEG) slowing, a quantitative electroencephalographic measure collected during a short period of wakeful rest.
We found that adults with ADHD were significantly sleepier than neurotypical controls during the cognitive task and that this on-task sleepiness contributed to cognitive performance deficits usually attributed to symptoms of ADHD. EEG slowing predicted severity of ADHD symptoms and diagnostic status, and was also related to daytime sleepiness. Frontal EEG slowing as well as increased frontal delta were especially prominent in adults with ADHD. We have validated and adapted an objective observer-rated measure for assessing on-task sleepiness that will contribute to future sleep research in psychology and psychiatry.
These findings indicate that the cognitive performance deficits routinely attributed to ADHD and often conceptualized as cognitive endophenotypes of ADHD are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. Daytime sleepiness plays a major role in cognitive functioning of adults with ADHD.
Mind wandering, emotional lability and sleep quality are currently mostly independently investigated but are all interlinked and play a major role is adult attention-deficit/ hyperactivity disorder (ADHD). Emotional lability is a core feature of the disorder, excessive mind wandering has recently been linked to symptoms and impairments of ADHD and poor sleep quality is experienced by a clear majority of adults with ADHD. All three phenomena lead to functional impairment in ADHD, however their relationship to each other and to ADHD symptom severity is not well understood. Here we used serial multiple mediation models to examine the influence of mind wandering, sleep quality and emotional lability on ADHD symptom severity. 81 adults diagnosed with ADHD participated in this study. We found that mind wandering and emotional lability predicted ADHD symptom severity and that mind wandering, emotional lability and sleep quality were all linked and significantly contributed to the symptomatology of adult ADHD. Mind wandering was found to lead to emotional lability which in turn lead to ADHD symptom severity; and poor sleep quality was found to exacerbate mind wandering leading to ADHD symptoms. Future research should employ objective on-task measures of mind wandering, sleepiness and emotional lability to investigate the neural basis of these impairing deficits in ADHD.
Tumor profiling tests can help to identify whether women with breast cancer need chemotherapy due to their risk of relapse, and some may be able to predict benefit from chemotherapy. We focused on four genetic tests: Oncotype DX (O-DX), MammaPrint (MMP), EndoPredict and Prosigna, and one immunohistochemistry test, IHC4, for the National Institute of Health and Care Excellence as part of their Diagnostic Appraisal Programme.
A systematic review was undertaken, including searching of nine databases in February 2017 plus other sources including a previous review published in 2013. The review included studies assessing clinical effectiveness of the five tumor profiling tests, with or without clinicopathological factors, to guide decisions about adjuvant chemotherapy in people with ER-positive, HER-2 negative, Stage I-II cancer with 0 to 3 positive lymph nodes (LN). The PROBAST tool and Cochrane risk of bias tools were used to assess risk of bias.
A total of 153 studies were included; the strength of evidence base for individual tests was varied. Results suggest all tests are prognostic for risk of relapse, though results were more varied in LN positive (+) patients than in LN negative (0) patients. Evidence was limited about whether tests can predict benefit from chemotherapy (available for MMP and O-DX only). Studies that assessed the impact of the tests on clinical decisions indicate that the net change in chemotherapy recommendations or decisions pre-/post-test ranged from an increase of one percent to a decrease of 23 percent among UK studies, and a decrease of zero percent to 64 percent across European studies.
The studies included in the review suggest that all of the tests can provide prognostic information on the risk of relapse; however results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence for prediction of chemotherapy benefit.
Rapid reviews are of increasing importance within Health Technology Assessment (HTA) due to the need for timely evidence to underpin the assessment of new technologies as well as financial constraints. There are many rapid review methods available (1) although there is little guidance as to the most suitable methods (2). A recent paper outlines issues to consider when selecting rapid review methods (3). The aim of this presentation is to present key aspects to consider when selecting rapid review methods.
We searched the evidence base for guidance on the selection of rapid review methods. We also examined three recently completed systematic reviews to identify rapid review methods used, the reasons for selection and the strengths and weaknesses of each method. Finally we identified key aspects to consider when selecting rapid review methods.
The evidence on guidance identified for the selection of rapid review methods was very limited. The analysis of the three reviews found that each review had distinctly different challenges, such as large numbers of relevant trials and heterogeneity in terms of populations, interventions, comparators and outcomes. All reviews included at least ten randomized controlled trials and numerous outcome measures. Three different approaches to the rapid review of the evidence were used in the three reviews. Key themes to consider when selecting rapid review methods were identified. These include: the size and nature of the evidence base, the characteristics of included studies and the expectations of those commissioning the review.
Rapid review methods need to be chosen to fit the needs of the review, each of which may have different challenges. Collaboration between those producing rapid reviews and commissioners is crucial when choosing methods to ensure that the needs of commissioners are met and limitations associated with the chosen methods are understood.
Multiple databases are often searched in Health Technology Assessment systematic reviews. However in rapid reviews, time and resources are limited and modifications to the search methodology may be necessary. In this retrospective study, the impact of searching fewer databases for three completed rapid reviews (i) Severe Mental Illness (SMI), (ii) Cannabis Cessation (CC), iii) Premature Ejaculation (PE) for the United Kingdom National Institute for Health Research was investigated.
The database coverage and indexing of the study references from the reviews were initially identified. The impact of fewer databases searched was then tested by (i) the number of studies that might be missed, (ii) the number of records for sifting and (iii) the overall rapid review conclusions.
A total of 178 included study references were found in the reviews (SMI n = 14 for 13 studies, CC n = 34 for 33 studies, PE n = 130 for 102 studies). Searching Medline only for SMI, Medline+Embase for CC, Medline+Embase+Cochrane Library for PE, would result in 1902 (74 percent), 466 (43 percent) and 240 (11 percent) fewer records needed to sift, respectively. There would also be a total of ten ‘would be missed’ references (SMI n = 1, CC n = 5 and PE n = 4). However, nine out of the ten references were found to have no or minimal impact on the overall findings of the reviews. The ten references were secondary reports of an included study, papers that lacked sufficient data for meta-analysis such as a conference abstract or an ongoing trial.
From the three reviews examined, limiting the search to fewer databases had no or minimal impact on the review conclusions despite the variable number of studies that would be missed and records needed to sift. More exploration during the scoping search prior to commencing the review will aid the decision on whether to limit the search to fewer databases.
Uveitis is inflammation inside the eye whose underlying cause may be infectious or non-infectious. The objective of our study was to assess the cost-effectiveness of the dexamethasone implant and adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or pan-uveitis.
A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the relevant evidence. Quality of life data collected in three key randomized-controlled trials (1-3) was used to estimate the interventions effectiveness compared with the trials comparator arms, which consisted of placebo plus limited current practice (LCP). An indirect treatment comparison between adalimumab and dexamethasone was considered inappropriate due to lack of necessary evidence. For adalimumab, patients with active and inactive uveitis were considered separately. Due to the short duration of the trials, the rate of blindness, an important complication of uveitis, was highly uncertain. Substantial exploratory analyses were therefore undertaken. The analysis was performed from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). Costs were calculated based on standard United Kingdom sources.
The estimated incremental cost-effectiveness (ICER) of dexamethasone compared with LCP was GBP19,509 per quality-adjusted life year (QALY) gained. The estimated ICER of adalimumab compared with LCP was GBP94,523 and GBP317,547 per QALY in patients with active and inactive uveitis respectively. The factors with the largest impact upon the ICERs were the rate of blindness and the proportion of cases of blindness avoided by interventions.
Dexamethasone and adalimumab resulted in health gains, but at significant extra costs, especially adalimumab which is unlikely to be considered a cost-effective use of NHS resources. The results of the analysis are highly uncertain due to the limited availability of evidence on: the comparative effectiveness of dexamethasone, adalimumab and current practice; the effectiveness of treatments in avoiding blindness; and, the effectiveness of interventions in different subgroups.
For many, Shakespeare represents the advent of modernity. It is easy to forget that he was in fact a writer deeply embedded in the Middle Ages, who inherited many of his shaping ideas and assumptions from the medieval past. This collection brings together essays by internationally renowned scholars of medieval and early modern literature, the history of the book and theatre history to present new perspectives on Shakespeare and his medieval heritage. Separated into four parts, the collection explores Shakespeare and his work in the context of the Middle Ages, medieval books and language, the British past, and medieval conceptions of drama and theatricality, together showing Shakespeare's work as rooted in late medieval history and culture. Insisting upon Shakespeare's complexity and medieval multiplicity, Medieval Shakespeare gives readers the opportunity to appreciate both Shakespeare and his period within the traditions that fostered and surrounded him.