Do sequential lineups impair underlying discriminability?

© 2020, The Author(s). Debate regarding the best way to test and measure eyewitness memory has dominated the eyewitness literature for more than 30 years. We argue that resolution of this debate requires the development and application of appropriate measurement models. In this study we developed models of simultaneous and sequential lineup presentations and used these to compare these procedures in terms of underlying discriminability and response bias, thereby testing a key prediction of diagnostic feature detection theory, that underlying discriminability should be greater for simultaneous than for stopping-rule sequential lineups. We fit the models to the corpus of studies originally described by Palmer and Brewer (2012, Law and Human Behavior, 36(3), 247–255), to data from a new experiment and to eight recent studies comparing simultaneous and sequential lineups. We found that although responses tended to be more conservative for sequential lineups there was little or no difference in underlying discriminability between the two procedures. We discuss the implications of these results for the diagnostic feature detection theory and other kinds of sequential lineups used in current jurisdictions

The clinical and cost-effectiveness of patient education models for diabetes : a systematic review and economic evaluation

Description of the proposed service This systematic review examines the clinical and cost-effectiveness of patient education models for adults with Type 1 or Type 2 diabetes. Epidemiology and background Diabetes mellitus (diabetes) is characterised by a state of chronic hyperglycaemia (raised blood sugar). There are two main types of diabetes: Type 1 and Type 2. Type 1 diabetes is an autoimmune condition involving a process of destruction of the beta cells of the pancreas, leading to severe insulin deficiency. About one-fifth of patients with diabetes in England and Wales have Type 1 diabetes. Type 2 diabetes is characterised by insulin resistance and relative insulin deficiency and is linked to being overweight or obese, and to physical inactivity. Type 2 diabetes primarily affects people aged over 40 years. The basic target in the treatment of diabetes is the normalisation of blood glucose levels. Poor control of diabetes can in the short term result in diabetic ketoacidosis, a serious and potentially fatal condition, and in the long term can increase the risk of complications such as diabetic retinopathy and nephropathy. However, studies have shown that good diabetic control is associated with a reduced risk of these complications. Diabetic control is affected by both lifestyle factors such as diet, and by pharmacological treatments, and the management of diabetes is largely the responsibility of patients. A key component in empowering patients to manage their own diabetes is education. Education of patients with diabetes is considered a fundamental aspect of diabetes care and aims to empower patients by improving knowledge and skills. Structured educational programmes for diabetes self-management are often multifaceted interventions providing patients with information not only about diabetes but also management issues such as diet, exercise, self-monitoring of blood glucose and medication use. Methods A systematic review of the literature and an economic evaluation were undertaken. Data sources Electronic databases were searched, including the Cochrane Library, MEDLINE, EMBASE, PubMed, Science Citation Index, Web of Science Proceedings, DARE and HTA databases, PsychINFO, CINAHL, NHS Economic Evaluation Database and EconLit. References of all retrieved articles were checked for relevant studies, and experts were contacted for advice and peer review and to identify additional published and unpublished references. Sponsor submissions to the National Institute for Clinical Excellence were reviewed. Study selection Studies were included if they fulfilled the following criteria: Interventions: educational interventions compared with usual care or another educational intervention. Participants: adults with Type 1 or Type 2 diabetes mellitus. Outcomes: must report glycated haemoglobin, hypoglycaemic episodes, diabetic complications or quality of life. Other reported outcomes from included studies were discussed. Evaluation of outcomes >12 months from inception of intervention. Design: randomised clinical trials (RCTs), and controlled clinical trial (CCTs) with a concurrent control were included. Reporting: studies were only included if they reported sufficient detail of the intervention to be reproducible (e.g. topics covered, who provided the education, how many sessions were available). Studies in non-English language or available only as abstracts were excluded. Titles and abstracts were checked by two reviewers. Full texts of selected studies were assessed for inclusion by one reviewer and checked by a second. Differences in opinion were resolved through discussion. Data extraction and quality assessment Data extraction and quality assessment were undertaken by one reviewer and checked by a second, with any disagreement resolved through discussion involving a third reviewer if necessary. The quality of included studies was assessed in accordance with Centre for Reviews and Dissemination Report 4. Data synthesis Data on clinical effectiveness were synthesised through a narrative review with tabulation of results from included studies. Studies were too diverse to be combined in a meta-analysis. Cost-effectiveness analyses were reported in a narrative review. Number and quality of studies Searches identified 24 studies comparing education with either a control group or with another educational intervention. These were 18 RCTs and six CCTs. Four studies included adults with Type 1 diabetes, 16 studies included adults with Type 2 diabetes and four studies included adults with either Type 1 or Type 2 diabetes. The quality of reporting and methodology of the studies was generally poor by today’s standards with only two RCTs reporting adequate randomisation procedures and none demonstrating adequate allocation concealment. Economic evaluations Literature searches identified only two studies reporting cost-effectiveness results: one cost-utility analysis and one cost-effectiveness analysis using intermediate outcomes only. Summary of benefits Studies of education in Type 1 diabetes suggest that education programmes offered as a part of intensified treatment interventions can result in significant and long-lasting improvements in metabolic control and reductions in complications. These are studies in which education is part of a package of care also including treatment changes (for example diet and insulin) and therefore it is not possible to draw conclusions about potential effects of education per se in Type 1 diabetes. Diverse educational programmes in Type 2 diabetes did not yield consistent results. Although some trials reported significant improvements in metabolic control and/or quality of life or other psychological outcomes, many others did not report significant effects of educational interventions. No clear characterisation is possible as to what features of education may be beneficial in this patient group. Studies that included patients with either Type 1 or Type 2 diabetes also produced mixed results with only poorer quality studies reporting significant effects. Costs Literature searches identified a small number of studies offering cost data in relation to patient education models. These were all studies undertaken outside the UK and they covered a variety of methodologies. We are not able to generalise from these studies as to the cost-effectiveness of patient education models. Patient education models will predominantly consist of direct costs for resource inputs to particular education packages, for example staff time (diabetes specialist nurse, dietitian and/or consultant) and education materials. The Dose Adjustment for Normal Eating (DAFNE) intervention is estimated to cost approximately £545 per person attending. Costs per life year gained Owing to the absence of accurate data on health outcomes, we are not able to provide cost-effectiveness summary statistics. The evidence base does indicate that improved glycaemic control is likely to have a positive impact on the incidence of long-term diabetic complications. Therefore, where the costs associated with patient education are assumed to be in the region of £500–600 per patient, the benefits over time would have to be very modest to offer an attractive cost-effectiveness profile for the intervention. The submission from the DAFNE study group predicts a scenario in which the DAFNE intervention results in cost savings and added health benefits over time, when compared with usual practice. Implications The main implication for the NHS would be staff time, particularly of diabetes specialist nurses, but also dietitians. Provision of increased education may be hindered by a shortage of trained specialist nurses, which will take some years to resolve. Future research needs The paucity of high-quality trials that have tested education per se in diabetes reveals a need for more research. Such research should focus on RCTs with clear designs based on explicit hypotheses and with a range of outcomes evaluated after long follow-up intervals. In order to draw conclusions about the effects of education alone, such trials should manipulate only education rather than confounding education with other factors

Self-Management Strategies Mediate Self-Efficacy and Physical Activity

Self-efficacy theory proposes that girls who have confidence in their capability to be physically active will perceive fewer barriers to physical activity or be less influenced by them, be more likely to pursue perceived benefits of being physically active, and be more likely to enjoy physical activity. Self-efficacy is theorized also to influence physical activity through self-management strategies (e.g., thoughts, goals, plans, and acts) that support physical activity, but this idea has not been empirically tested

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients