Explore the vast range of titles available.

Background Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA—the IDIOM score. The aim of this retrospective observational study was to validate the IDIOM model using two independent external datasets. Methods The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets. Results The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups’ calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than ‘investigate all’ and ‘investigate no-one’ strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets. Conclusion This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings.

IntroductionThe investigation of iron deficiency anaemia (IDA) in the over 80-year-olds presents a unique challenge due to co-morbidity, uncertain prognosis and differing attitudes to acceptability of invasive investigation. We evaluated the investigations accepted and the subsequent outcomes for elderly patients.MethodsWe prospectively collected consecutive GP referrals of IDA patients aged 80+ between 2015 and 2018 seen by a single gastroenterologist. The options of invasive investigation (bidirectional endoscopy), non-invasive investigation (CTC – CT pneumocolon; CT long oral prep; CT TAP – CT thorax, abdomen, pelvis), or no investigation, were discussed and offered in a standardised manner.Results173 patients (64.7% female, 80–95 yrs) were seen. 28 (16.2%) declined all investigations, while 39 (22.5%) underwent bidirectional endoscopy. Investigations accepted and performed were: OGD 93 (53.7%), colonoscopy 40 (23.1%), CTC 52 (30%), CT long oral prep 47 (27.2%), and CT TAP 34 (19.7%). Carcinoma was identified in 21 (14.5%) patients who underwent investigations - 19 (13.1%) were gastrointestinal (GI) cancers (16 colorectal, 3 gastric), one metastatic. Two patients with GI malignancy were also diagnosed with myeloma. The 2 non-GI cancers were metastatic renal cell carcinoma and hepatocellular carcinoma. There were significant differences in investigations undertaken between the elderly (80–84 yrs) and very elderly (85+yrs) as shown in the table 1.Abstract P370 Table 1 AGE GROUP n= number 80– 84 (n= 99) 85+ (n= 74) χ 2 comparison of age group Declined all investigations 9 (9%) 19 (26%) P<0.01 Bidirectional endoscopy 37 (37%) 2 (3%) P<0.00001 Colonoscopy 38 (38%) 2 (3%) P<0.00001 OGD 62 (63%) 31 (42%) P<0.01 CTC 28 (28%) 24 (32%) P=0.55 CT long oral prep 21 (21%) 26 (35%) P<0.05 CT TAP 13 (13%) 20 (27%) P<0.03 Of the 17 potentially operable GI cancers, 9 procedures with curative intent were performed (8 hemicolectomy, 1 transanal resection). Two of these were in patients aged 85+. 1 subject, aged 89, was offered curative surgery but declined. Outcomes from surgery were very positive, with 8/9 patients undergoing surgery still alive (median follow up 984 days, range 454–2151). The single death occurred 1247 days post-clinic. This compared with on-going survival of 2/8 patients who did not undergo surgery (421 and 701 days), with a median survival of 495 days (range 93–1562) for those who died.ConclusionsThe over 80-year-olds with IDA are a heterogeneous group. Overall 16% of patients declined all investigations, though this rose to 26% in those aged over 85. Non-invasive tests were much more likely to be undertaken in the 85+ age group, with only 3% having ‘gold standard’ bidirectional endoscopy. Half of patients with potentially curable GI cancers discovered underwent surgery, with 8/9 alive at a mean follow-up of 2.5 years.

Both clinical and experimental studies have reported that mild traumatic brain injury (mTBI) can result in cognitive impairments in the absence of overt brain damage. Whether these impairments result from neuronal dysfunction/altered plasticity is an area that has received limited attention. In this study, we recorded activity of neurons in the cornu Ammonis (CA)1 subfield of the hippocampus in sham and mild lateral fluid percussion injured (mFPI) rats while these animals were performing an object location task. Electrophysiology results showed that the number of excitatory neurons encoding spatial information (i.e., place cells) was reduced in mFPI rats, and that these cells had broader and less stable place fields. Additionally, the in-field firing rate of place cells in sham operated, but not in mFPI, animals increased when objects within the testing arena were moved. Immunostaining indicated no visible damage or overall neuronal loss in mFPI brain sections. However, a reduction in the number of parvalbumin-positive inhibitory neurons in the CA1 subfield of mFPI animals was observed, suggesting that this reduction could have influenced place cell physiology. Alterations in spatial information content, place cell stability, and activity in mFPI rats coincided with poor performance in the object location task. These results indicate that altered place cell physiology may underlie the hippocampus-dependent cognitive impairments that result from mTBI.

Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer that Narp knockout mice undergo normal seizure activity in this paradigm, yet fail to display antidepressant-like behavioral effects of ECS. Although Narp deletion does not suppress ECS-induced proliferation in the dentate gyrus, it blocks dendritic outgrowth of immature granule cell neurons in the dentate molecular layer induced by ECS. Taken together, these findings indicate that Narp contributes to the antidepressant action of ECT and implicate the ability of ECS to induce dendritic arborization of differentiating granule cells as a relevant step in eliciting this response.