SPICED-ACS: Study of the potential impact of a computer-generated ECG diagnostic algorithmic certainty index in STEMI diagnosis: Towards transparent AI.

BACKGROUND: Computerised electrocardiogram (ECG) interpretation diagnostic algorithms have been developed to guide clinical decisions like with ST segment elevation myocardial infarction (STEMI) where time in decision making is critical. These computer-generated diagnoses have been proven to strongly influence the final ECG diagnosis by the clinician; often called automation bias. However, the computerised diagnosis may be inaccurate and could result in a wrong or delayed treatment harm to the patient. We hypothesise that an algorithmic certainty index alongside a computer-generated diagnosis might mitigate automation bias. The impact of reporting a certainty index on the final diagnosis is not known. PURPOSE: To ascertain whether knowledge of the computer-generated ECG algorithmic certainty index influences operator diagnostic accuracy. METHODOLOGY: Clinicians who regularly analyse ECGs such as cardiology or acute care doctors, cardiac nurses and ambulance staff were invited to complete an online anonymous survey between March and April 2019. The survey had 36 ECGs with a clinical vignette of a typical chest pain and which were either a STEMI, normal, or borderline (but do not fit the STEMI criteria) along with an artificially created certainty index that was either high, medium, low or none. Participants were asked whether the ECG showed a STEMI and their confidence in the diagnosis. The primary outcomes were whether a computer-generated certainty index influenced interpreter's diagnostic decisions and improved their diagnostic accuracy. Secondary outcomes were influence of certainty index between different types of clinicians and influence of certainty index on user's own-diagnostic confidence. RESULTS: A total of 91 participants undertook the survey and submitted 3262 ECG interpretations of which 75% of ECG interpretations were correct. Presence of a certainty index significantly increased the odds ratio of a correct ECG interpretation (OR 1.063, 95% CI 1.022-1.106, p = 0.004) but there was no significant difference between correct certainty index and incorrect certainty index (OR 1.028, 95% CI 0.923-1.145, p = 0.615). There was a trend for low certainty index to increase odds ratio compared to no certainty index (OR 1.153, 95% CI 0.898-1.482, p = 0.264) but a high certainty index significantly decreased the odds ratio of a correct ECG interpretation (OR 0.492, 95% CI 0.391-0.619, p < 0.001). There was no impact of presence of a certainty index (p = 0.528) or correct certainty index (p = 0.812) on interpreters' confidence in their ECG interpretation. CONCLUSIONS: Our results show that the presence of an ECG certainty index improves the users ECG interpretation accuracy. This effect is not seen with differing levels of confidence within a certainty index, with reduced ECG interpretation success with a high certainty index compared with a trend for increased success with a low certainty index. This suggests that a certainty index improves interpretation when there is an increased element of doubt, possibly forcing the ECG user to spend more time and effort analysing the ECG. Further research is needed looking at time spent analysing differing certainty indices with alternate ECG diagnoses.

NLRP3 as a potentially novel biomarker for the management of osteoarthritis.

Osteoarthritis (OA) was previously thought of as 'wear and tear' as humans age, however there is increasing evidence to support an inflammatory theory. The nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) inflammasome has been implicated in the pathogenesis of a number of arthritic disorders, producing proinflammatory cytokines and degradative enzymes such as Interleukin-1 beta (IL-1ß), Tumour necrosis factor alpha (TNF-α) and Matrix metalloproteinase-3 (MMP-3) which drive cartilage degeneration and synovial inflammation. This review aims to summarise the evidence of NLRP3 involvement in OA. Currently, treatment options focus on management of the disease and to date there is no cure. The development of novel biomarkers for OA could improve diagnosis, treatment and management. Importantly, this review provides detail on the involvement of the NLRP3 inflammasome in OA pathology and how its members could act as potential biomarkers to assist clinical decisions.

The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers.

Ulcerative colitis is characterised by impairment of the epithelial barrier and tight junction alterations resulting in increased intestinal permeability. UC is less common in smokers with smoking reported to decrease paracellular permeability. The aim of this study was thus to determine the effect of nicotine, the major constituent in cigarettes and its metabolites on the integrity of tight junctions in Caco-2 cell monolayers. The integrity of Caco-2 tight junctions was analysed by measuring the transepithelial electrical resistance (TER) and by tracing the flux of the fluorescent marker fluorescein, after treatment with various concentrations of nicotine or nicotine metabolites over 48 h. TER was significantly higher compared to the control for all concentrations of nicotine 0.01-10 microM at 48 h (p<0.001), and for 0.01 microM (p<0.001) and 0.1 microM and 10 microM nicotine (p < 0.01) at 12 and 24 h. The fluorescein flux results supported those of the TER assay. TER readings for all nicotine metabolites tested were also higher at 24 and 48 h only (p < or = 0.01). Western blot analysis demonstrated that nicotine up-regulated the expression of the tight junction proteins occludin and claudin-1 (p < or = 0.01). Overall, it appears that nicotine and its metabolites, at concentrations corresponding to those reported in the blood of smokers, can significantly improve tight junction integrity, and thus, decrease epithelial gut permeability. We have shown that in vitro, nicotine appears more potent than its metabolites in decreasing epithelial gut permeability. We speculate that this enhanced gut barrier may be the result of increased expression of claudin-1 and occludin proteins, which are associated with the formation of tight junctions. These findings may help explain the mechanism of action of nicotine treatment and indeed smoking in reducing epithelial gut permeability.

Concordance between common dry eye diagnostic tests.

AIM: Large variations in results of diagnostic tests for mild to moderate dry eye are widely recognised. The purpose of this study was to assess if there was concordance between common dry eye diagnostic tests. METHODS: A total of 91 subjects were recruited to the study. The tear film and ocular surface were evaluated using the phenol red thread test (PRT), tear film break-up time (TBUT), biomicroscopic examination and impression cytological assessment of conjunctival goblet cells. Dry eye symptoms were assessed using McMonnies' dry eye questionnaire (MQ) and statistical correlations between all tests were assessed. RESULTS: This study cohort did not include severe aqueous deficient dry eye patients as determined by the PRT. A statistically significant difference was noted between PRT results and all other tests (p