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.

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake.

AIMS/HYPOTHESIS: Decreasing mitochondrial coupling efficiency has been shown to be an effective therapy for obesity and related metabolic symptoms. Here we identified a novel mitochondrial uncoupler that promoted uncoupled respiration in a cell type-specific manner and investigated its effects on modulation of energy metabolism in vivo and in vitro. METHODS: We screened a collection of mitochondrial membrane potential depolarising compounds for a novel chemical uncoupler on isolated skeletal muscle mitochondria using a channel oxygen system. The effect on respiration of metabolic cells (L6 myotubes, 3T3-L1 adipocytes and rat primary hepatocytes) was examined and metabolic pathways sensitive to cellular ATP content were also evaluated. The chronic metabolic effects were investigated in high-fat diet-induced obese mice and standard diet-fed (SD) lean mice. RESULTS: The novel uncoupler, CZ5, promoted uncoupled respiration in a cell type-specific manner. It stimulated fuel oxidation in L6 myotubes and reduced lipid accumulation in 3T3-L1 adipocytes but did not affect gluconeogenesis or the triacylglycerol content in hepatocytes. The administration of CZ5 to SD mice increased energy expenditure (EE) but did not affect body weight or adiposity. Chronic studies in mice on high-fat diet showed that CZ5 reduced body weight and improved glucose and lipid metabolism via both increased EE and suppressed energy intake. The reduced adiposity was associated with the restoration of expression of key metabolic genes in visceral adipose tissue. CONCLUSIONS/INTERPRETATION: This work demonstrates that a cell type-specific mitochondrial chemical uncoupler may have therapeutic potential for treating high-fat diet-induced metabolic diseases.

Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding.

AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.

Early experience of a CT coronary angiography service in a Scottish regional centre.

BACKGROUND: CT coronary angiography (CTCA) is an emerging diagnostic tool in the assessment of patients with suspected coronary artery disease. It has several advantages over conventional coronary angiography (CCA); however, its use is not yet widespread in large teaching centres. AIMS: To determine what proportion of patients who have CTCA, do not require subsequent CCA. METHODS: A prospective analysis of all patients referred for CTCA from the start of the service in January 2008 to April 2010. RESULTS: CTCA provided definitive diagnostic images in 85% of patients. Overall only 12% (n = 33) of patients had subsequent CCA. The proportion of patients who subsequently had CCA reduced with time reflecting increasing confidence with the clinical service. CONCLUSIONS: A CTCA service can be successfully established out with a large teaching centre hospital. Close working between cardiologists and radiologists leads to increased confidence in the service and obviates the need for CCA in a large proportion of patients.

Weight assessment in cardiac patients: implications for prescription of low molecular weight heparin.

BACKGROUND: Many drugs such as low molecular weight heparin (LMWH) are administered at "patient weight adjusted" doses. Obtaining an accurate measurement of a patient's weight may not always be possible. The aim of this study was to assess patterns and accuracy of weight estimation and implications for drug dosing. METHODS: The study comprised three parts: (1) inpatient weight documentation was reviewed over a 4 week period (January 2008); (2) a questionnaire was distributed to healthcare staff; (3) healthcare staff were asked to estimate the weight of patients. These estimates took place in three locations: the coronary care unit, cardiac catheterisation laboratory, and the cardiac outpatient department. RESULTS: (1) In 385 patient notes, only 192 (49.9%) had a record of the patient's weight. The dose of LMWH was correct only 51% of the time. (2) Doctors were more likely to estimate a patient's weight than nurses (85 vs 51%, p = 0.003). (3) 50 healthcare staff made 533 weight estimations on 182 patients. There was a tendency to overestimate the weight of lighter patients and underestimate the weight of heavier patients (p<0.001). Patients were more accurate than healthcare staff at estimating their weight (80% vs 39%, p<0.001) and female patients were more likely to be accurate than men (62% vs 44%, p = 0.035). CONCLUSIONS: In our institution weight estimation occurs and may result in inaccurate prescription of LMWH. Estimating a patient's weight should be discouraged but if necessary the patient reported weight is likely to be most accurate. Unless there is significant investment in improved technology to allow obese or acutely unwell patients to be weighed, the dangerous practice of weight estimation is likely to continue.

Preliminary study of hypoxia-related cardiovascular mediator-markers in patients with end-stage renal disease with and without diabetes and the effects of haemodialysis.

BACKGROUND: Evidence points to activation of pro-inflammatory and pro-thrombotic stimuli during the haemodialysis process in end-stage renal disease (ESRD) with potential to predispose to cardiovascular events. Diabetes is associated with a higher incidence of cardiovascular disease in haemodialysis patients. We tested the hypothesis that a range of mediators and markers that modulate cardiovascular risk are elevated in haemodialysis patients with diabetes compared to those without. METHODS: Men and women with diabetes (n = 6) and without diabetes (n = 6) aged 18-90 years receiving haemodialysis were recruited. Blood samples were collected and analysed pre- and post-haemodialysis sessions for (platelet-monocyte conjugates (PMC), oxidised LDL (Ox-LDL), endothelin 1 (ET-1) and vascular endothelial growth factor (VEGF-A). RESULTS: PMC levels significantly increased after haemodialysis in both groups (diabetes p = 0.047; non-diabetes p = 0.005). Baseline VEGF-A was significantly higher in people with diabetes (p = 0.009) and post-dialysis levels were significantly reduced in both groups (P = 0.002). Ox-LDL and CRP concentrations were not significantly different between groups nor affected in either group post-dialysis. Similarly, ET-1 concentrations were comparable in all patients at baseline, with no change post-dialysis in either group. CONCLUSIONS: In this pilot study, we have confirmed that circulating PMCs are increased following dialysis irrespective of diabetes status. This is likely to be a mechanistic process and offers a potential explanation for high rates of vascular events associated with haemodialysis. The higher VEGF-A concentrations between patients with and without diabetes is a previously unreported finding in diabetic ESRD. Further research is merited to establish whether VEGF-A is a marker or mediator (or both) of cardiovascular risk in haemodialysis.

Clinical features remain important for the diagnosis of infective endocarditis in the modern era.

BACKGROUND: Infective endocarditis (IE) can be difficult to diagnose, due to multiple (often non-specific) presenting features. AIM: To assess the predictive accuracy of classical clinical features and blood investigations readily available at the time of presentation. DESIGN: Cross-sectional analysis. METHODS: We studied 29 IE cases and 79 controls (clinically suspicious contemporaneous cases where IE was subsequently excluded) from a hospital-based group of patients referred to a cardiac department with possible infective endocarditis. Patients were identified from the echocardiography database. Cases were defined by final diagnosis. Symptoms, signs, risk factors for IE and blood investigations were recorded from case notes and examined by univariate and multivariate analyses. RESULTS: The sensitivity, specificity, and positive and negative predictive values of transthoracic echocardiography (TTE) for detection of IE in clinically suspected cases were 71%, 98%, 57% and 99%, respectively. Univariate analyses revealed a significant association between IE and several clinical features. Under multivariate analysis, previous heart valve surgery (OR 13.3, 90%CI 3.2-55.6), positive blood cultures (OR 17.2, 90%CI 4.9-58.8), signs of embolism (OR 11.4, 90%CI 3.0-43.5), a new, altered or changing murmur (OR 10.3, 90%CI 2.8-38.5) and splenomegaly (OR 18.2, 90%CI 3.6-90.9) were independent predictors for IE. DISCUSSION: Clinical features at presentation continue to be important for the diagnosis of IE. Features such as positive blood cultures, signs of embolism and a changing heart murmur should be used to guide investigation and treatment of IE prior to echocardiography, or when TTE is negative.

Risk stratification in acute coronary syndromes--does the TIMI risk score work in unselected cases?

BACKGROUND: Management of patients with an acute coronary syndrome (ACS) requires accurate risk stratification to guide appropriate therapy. AIM: To assess the utility of the TIMI risk score in stratifying patients with possible ACS in routine clinical practice. DESIGN: Prospective observational study. METHODS: We recruited 869 consecutive patients with a diagnosis of possible ACS attending the acute medical receiving unit of a district general hospital. The main outcome measures were recurrent myocardial infarction, urgent revascularization, and all-cause mortality. TIMI risk score was calculated for each patient, and each was also assigned a risk group based on electrocardiogram (ECG) changes and troponin levels only. After follow-up, Cox univariate and multivariate regression was used to evaluate the influence of potential risk factors on duration of event-free survival, and likelihood ratio tests to assess the fit of the models. RESULTS: Increasing TIMI risk score was associated with increased risk of events (p<0.001), as was higher risk group from ECG plus troponin stratification (p<0.001). The likelihood ratio comparison favoured the TIMI risk score (difference 13.910, 5 degrees of freedom, p = 0.016). DISCUSSION: The TIMI risk score is a valid tool for risk stratification in unselected cases with possible acute coronary syndrome. It is superior to ECG changes and troponin alone, although this simpler method also achieves good risk stratification.

Urgent in-patient coronary angiography: a comparison of centres with and without cardiac catheter facilities.

OBJECTIVES: To review the referral of patients to a tertiary centre for urgent angiography and to determine if there are differences in invasive treatment strategies for patients with acute coronary syndrome (ACS). METHODS: There were 2 parts to the study, a retrospective part over 3.5 years from a computerised cardiac laboratory booking data base and a prospective part over 3 months. RESULTS: There were 1190 urgent in-patient angiograms performed with 499 (42%) admitted initially to the tertiary centre while the remaining 691 (58%) were admitted to district general hospitals (DGH), with no on-site access to a cardiac laboratory, and subsequently transferred to the tertiary centre. Once referred, DGH patients waited longer for their angiogram (2.7 +/- 3.2 vs 2.0 +/- 2.8 days, p < 0.0001). Interestingly, DGH patients appear to spend an average of 4 days in hospital prior to referral for angiography. DGH patients were more likely to have a higher Thrombosis in Myocardial Infarction (TIMI) risk score at presentation and following angiography were more likely to have coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) and less likely to have angiographically normal arteries. CONCLUSIONS: Our findings are consistent with previous studies demonstrating that access to coronary angiography varies considerably between hospitals. However, we have demonstrated that patients in DGHs wait on average 4 days before referral for coronary angiography suggesting that there may be triage based on initial responses to medical therapy. Further research is needed to determine whether this has a direct effect on outcomes.

Potential costs of B-type natriuretic peptide for the identification of people with heart failure in primary care in Scotland - a pilot study.

BACKGROUND AND AIMS: The utility of B-type natriuretic peptide as a screening test for heart failure has been proven in a number of clinical trials. The aims of this study were to assess the utility of the measurement of B-type natriuretic peptide in a 'real life' setting and to estimate the potential costs of implementing its use in primary care in Scotland. METHODS AND RESULTS: Eight general practitioner practices with a combined population of approximately 62,000 were invited to participate. During the 9-month study period, 82 samples for B-type natriuretic peptide measurement were requested. The negative predictive value for B-type natriuretic peptide was 96.9%. Compared with electrocardiography, B-type natriuretic peptide reduced the need for echocardiography by 308 tests per million population per year. The estimated cost of implementation in Scotland is approximately £220,000 per annum, equating to £64.93 per patient correctly diagnosed with heart failure, with a potential saving in echocardiography of £110,800. CONCLUSION: In this pilot study, measurement of plasma B-type natriuretic peptide in a 'real life' setting in primary care had a similar sensitivity, specificity and negative predictive value to that observed in trial populations. B-type natriuretic peptide aids early diagnosis of heart failure in primary care and may help to facilitate prompt introduction of evidence based therapies to modify patient outcomes. The costs of measuring plasma B-type natriuretic peptide in suspected cases of heart failure are modest, and its use would increase the diagnostic capacity of primary care if supported by local cardiology services.

Case of a late presentation of cor triatriatum in a woman born with an imperforate anus.

Cor triatriatum and imperforate anus are rare. We describe, for the first time, the coexistence of these conditions in a 43 year old woman.

Physician opinions on the implementation of the SIGN guideline for heart failure.

BACKGROUND AND AIMS: To assess physician opinion of and attitudes to, the Scottish Intercollegiate Guideline Network (SIGN) guideline for chronic heart failure (CHF) due to left ventricular systolic dysfunction. METHODS AND RESULTS: A questionnaire examining physicians' attitudes and their use of the SIGN guideline for CHF was distributed to 158 physicians in two teaching hospitals within one NHS trust. 65% of recipients responded. More cardiologists had read the guideline compared to non-cardiologists (91 vs 56%, p < 0.05). The majority of cardiologists and non-cardiologists agreed that it was applicable to their patients (92 vs 79%, p > 0.1) and that implementation may reduce hospital admissions (65 vs 59%, p > 0.5). In general, compliance was thought to be a problem in only a minority of patients in both groups for angiotensin converting enzyme inhibitors (8 vs 19%), diuretics (12 vs 29%) and digoxin (17 vs 19%, all p > 0.1). Beta-blocker compliance was identified as a problem by both groups (50 vs 53%, P > 0.5) while fewer cardiologists reported compliance as a problem with spironolactone (4 vs 25%, p < 0.05). More cardiologists felt that there was a need for a community based CHF nurse specialist (100 vs 57%, p < 0.001), and that this strategy would reduce hospital admissions (92 vs 57%, p < 0.01). CONCLUSIONS: Differences exist between cardiologist and non-cardiologist physicians' awareness of the SIGN guideline for CHE. Furthermore, we have shown differences in reported implementation of the guideline and perceived difficulties with specific drug therapies. This is in spite of high levels of agreement in both groups with the treatment suggested by the guideline and the anticipated benefits resulting from its implementation.

Why people seek complementary and alternative medicine before conventional medical treatment: a population based study.

BACKGROUND: Few studies explain peoples' intentions to use complementary and alternative medicine (CAM) before conventional medicine. AIMS: To examine the psychosocial factors associated with intention to try CAM before conventional medicine; to explore the predictors of initially seeking CAM in the adult population in Australia. DESIGN: A cross sectional survey. METHODS: 1256 adults were interviewed as part of 2012 Queensland Social Survey. Relationships were explored using logistic regression. RESULTS: 79% of respondents had used CAM in the last 12 months; 17.6% of people would try CAM before conventional medicine. Age, education, perceived control and spirituality predicted intention to try CAM before conventional medicine. People often sought CAM initially to improve their health and well-being. CONCLUSION: Personal characteristics and psychosocial factors predicted intention to try CAM before conventional medicine. These factors need to be considered by doctors and other conventional health care providers as part of person centred approaches to healthcare.

Psychosocial factors that predict why people use complementary and alternative medicine and continue with its use: a population based study.

UNLABELLED: Studies have explored the predictors of CAM use but fewer data explain the psychosocial factors associated with this and why people continue with CAM. AIMS: To examine the psychosocial factors that predict CAM use; to explore the predictors of continuing with CAM. DESIGN: A cross sectional survey. METHODS: 1256 adults were interviewed as part of 2012 Queensland Social Survey. We included questions about CAM, perceived control, cognitive style, spirituality and openness. Relationships were explored using bivariate and multiple logistic regression. RESULTS: 79% of people had used CAM in the last 12 months. Socio-demographics, health behaviours, spirituality, openness and prescribing sources were the strongest predictors of CAM use. General health, chronic illness and prescribing sources predicted continued CAM use. CONCLUSION: There was high CAM use in Queensland, Australia. Personal characteristics and psychosocial factors need to be considered as part of the individual's holistic assessment and on-going care.

Patient Reported Experience Measures (PREMs) in chronic heart failure.

BACKGROUND: Patient Reported Experience Measures (PREMs) is an essential tool for assessing the quality of chronic disease management. The optimal method for delivering a PREMs survey however is unknown. This study reports two methods for assessing PREMs in patients with chronic heart failure (CHF). METHODS: A bespoke online and postal survey delivered to community-based CHF patients in Scotland. RESULTS: A total of 121 patients (73 postal and 48 online) completed the survey. The online cohort were younger, had less contact with a CHF nurse, were more likely to see a CHF doctor and seemed less satisfied with the quality of clinical services. The postal cohort returned fewer negative comments (20 [27.4%] vs 28 [58.3%]; p<0.0001). Several recurring themes were identified. CONCLUSIONS: There are differences in participation rates and responses between postal and online surveys; the accuracy of the feedback gathered using these methods is therefore difficult to determine. Clinicians should consider offering a range of options to enable patients to reflect and 'voice' their opinions regarding clinical services.

Radiation dose at CT coronary angiography: how low can we go?

Computed tomography (CT) coronary angiography is now a widely available and reliable test accessible on basic CT platforms that can exclude coronary heart disease with confidence. It is fast, cheap and, if properly carried out by trained and accredited staff in carefully selected patients, useful information can be obtained with acceptably low radiation exposure in some cases.

The adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway.

APPL1 is an adaptor protein that binds to both AKT and adiponectin receptors and is hypothesised to mediate the effects of adiponectin in activating downstream effectors such as AMP-activated protein kinase (AMPK). We aimed to establish whether APPL1 plays a physiological role in mediating glycogen accumulation and insulin sensitivity in muscle and the signalling pathways involved. In vivo electrotransfer of cDNA- and shRNA-expressing constructs was used to over-express or silence APPL1 for 1 week in single tibialis cranialis muscles of rats. Resulting changes in glucose and lipid metabolism and signalling pathway activation were investigated under basal conditions and in high-fat diet (HFD)- or chow-fed rats under hyperinsulinaemic-euglycaemic clamp conditions. APPL1 over-expression (OE) caused an increase in glycogen storage and insulin-stimulated glycogen synthesis in muscle, accompanied by a modest increase in glucose uptake. Glycogen synthesis during the clamp was reduced by HFD but normalised by APPL1 OE. These effects are likely explained by APPL1 OE-induced increase in basal and insulin-stimulated phosphorylation of IRS1, AKT, GSK3ß and TBC1D4. On the contrary, APPL1 OE, such as HFD, reduced AMPK and acetyl-CoA carboxylase phosphorylation and PPARγ coactivator-1α and uncoupling protein 3 expression. Furthermore, APPL1 silencing caused complementary changes in glycogen storage and phosphorylation of AMPK and PI3-kinase pathway intermediates. Thus, APPL1 may provide a means for crosstalk between adiponectin and insulin signalling pathways, mediating the insulin-sensitising effects of adiponectin on muscle glucose disposal. These effects do not appear to require AMPK. Activation of signalling mediated via APPL1 may be beneficial in overcoming muscle insulin resistance.

Unemployment and deprivation are associated with a poorer outcome following percutaneous coronary angioplasty.

This prospective observational study aimed to assess the impact of employment status and deprivation on quality of life 12 months after percutaneous coronary intervention (PCI). Patients completed a questionnaire at baseline and at 1 year follow-up including a health utility score (EQ-5D), symptoms and employment status. Deprivation was assessed using the Carstairs' deprivation category based on area postcodes. The majority (79.6%) of patients of working age returned to work within 12 months. Unemployment was associated with a lower quality of life (QoL) at baseline (0.49 (0.32) vs 0.61 (0.27), p=0.002) and less improvement in QoL 1 year after PCI (0.15 (0.37) vs 0.26 (0.31), p<0.012). Furthermore, unemployed patients had significantly less improvement in chest pain score (p=0.002) and breathlessness (p<0.001). Unemployed patients from the most deprived areas had lowest QoL at follow-up and least improvement in QoL at 1 year. Unemployment and deprivation are associated with poorer outcomes following PCI.