Concordance between point-of-care blood gas analysis and laboratory autoanalyzer in measurement of hemoglobin and electrolytes in critically ill patients.

BACKGROUND: We tested the hypothesis that the results of the same test performed on point-of-care blood gas analysis (BGA) machine and automatic analyzer (AA) machine in central laboratory have high degree of concordance in critical care patients and that the two test methods could be used interchangeably. METHODS: We analyzed 9398 matched pairs of BGA and AA results, obtained from 1765 patients. Concentration pairs of the following analytes were assessed: hemoglobin, glucose, sodium, potassium, chloride, and bicarbonate. We determined the agreement using concordance correlation coefficient (CCC) and Bland-Altman analysis. The difference in results was also assessed against the United States Clinical Laboratory Improvement Amendments (US-CLIA) 88 rules. The test results were considered to be interchangeable if they were within the US-CLIA variability criteria and would not alter the clinical management when compared to each other. RESULTS: The median time interval between sampling for BGA and AA in each result pair was 5 minutes. The CCC values ranged from 0.89(95% CI 0.89-0.90) for chloride to 0.98(95% CI 0.98-0.99) for hemoglobin. The largest bias was for hemoglobin. The limits of agreement relative to bias were largest for sodium, with 3.4% of readings outside the US-CLIA variation rule. The number of readings outside the US-CLIA acceptable variation was highest for glucose (7.1%) followed by hemoglobin (5.9%) and chloride (5.2%). CONCLUSION: We conclude that there is moderate to substantial concordance between AA and BGA machines on tests performed in critically ill patients. However, the two tests methods cannot be used interchangeably, except for potassium.

Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of >100 patients.

OBJECTIVE: Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures. METHODS: The International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital. RESULTS: Data regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3-33.9 years), with median age of 6 weeks (range = 1 day-65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9-24). Changes in seizure activity after commencing KD were reported for two-thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one-third (31.7%) experienced side effects during the diet. At ascertainment, only one-third (32%) remained on the diet, with lack of long-term efficacy as the main reason for diet cessation (51%, 36 of 70). SIGNIFICANCE: Benefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long-term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician.

Optimal door-to-balloon time for primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Door-to-balloon time (DTBT) for ST-elevation myocardial infarction (STEMI) is a performance metric by which primary percutaneous coronary intervention (PPCI) services are assessed. METHODS: Consecutive patients presenting with STEMI undergoing PPCI between January 2007 to December 2019 from the Singapore Myocardial Infarction Registry were included. Patients were stratified based on DTBT (≤60 min, 61-90 min, 91-180 min) and Killip status (I-III vs. IV). Outcomes assessed included all-cause mortality and major adverse cardiovascular events (MACE) at 30-days and 1-year. RESULTS: In total, 13,823 patients were included, with 82.59% achieving DTBT ≤90 min and 49.77% achieving DTBT ≤60 min. For Killip I-III (n = 11,591,83.85%), the median DTBT was 60[46-78]min. The 30-day all-cause mortality for DTBT of ≤60 min, 61-90 min and 91-180 min was 1.08%, 2.17% and 4.33% respectively (p < 0.001). On multivariate analysis, however, there was no significant difference for 30-day and 1-year outcomes across all DTBT (p > 0.05). For Killip IV, the median DTBT was 68[51-91]min. The 30-day all-cause mortality for DTBT of ≤60 min, 61-90 min and 91-180 min was 11.74%, 20.48% and 35.06% respectively (p < 0.001). On multivariate analysis for 30-day and 1-year outcomes, DTBT 91-180 min was an independent predictor of worse outcomes (p < 0.05), but there was no significant difference between DTBT of ≤60 min and 61-90 min (p > 0.05). CONCLUSION: In Killip I-III patients, DTBT had no significant impact on outcomes upon adjustment for confounders. Conversely, for Killip IV patients, a DTBT of >90 min was associated with significantly higher adverse outcomes, with no differences between a DTBT of ≤60 min vs. 61-90 min. Outcomes in STEMI involve a complex interplay of factors and recommendations of a lowered DTBT of ≤60 min will require further evaluation.

Early Coronary Angiography Is Associated with Improved 30-Day Outcomes among Patients with Out-of-Hospital Cardiac Arrest.

We evaluated the association between early coronary angiography (CAG) and outcomes in resuscitated out-of-hospital cardiac arrest (OHCA) patients, by linking data from the Singapore Pan-Asian Resuscitation Outcomes Study, with a national registry of cardiac procedures. The 30-day survival and neurological outcome were compared between patients undergoing early CAG (within 1-calender day), versus patients not undergoing early CAG. Inverse probability weighted estimates (IPWE) adjusted for non-randomized CAG. Of 976 resuscitated OHCA patients of cardiac etiology between 2011-2015 (mean(SD) age 64(13) years, 73.7% males), 337 (34.5%) underwent early CAG, of whom, 230 (68.2%) underwent PCI. Those who underwent early CAG were significantly younger (60(12) vs. 66(14) years old), healthier (42% vs. 59% with heart disease; 29% vs. 44% with diabetes), more likely males (86% vs. 67%), and presented with shockable rhythms (69% vs. 36%), compared with those who did not. Early CAG with PCI was associated with better survival and neurological outcome (adjusted odds ratio 1.91 and 1.82 respectively), findings robust to IPWE adjustment. The rates of bleeding and stroke were similar. CAG with PCI within 24 h was associated with improved clinical outcomes after OHCA, without increasing complications. Further studies are required to identify the characteristics of patients who would benefit most from this invasive strategy.

Variable computed tomography appearances of COVID-19.

The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. Evolution of CT findings was observed in one patient, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, the use of CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.

Technical and imaging factors influencing performance of deep learning systems for diabetic retinopathy.

Deep learning (DL) has been shown to be effective in developing diabetic retinopathy (DR) algorithms, possibly tackling financial and manpower challenges hindering implementation of DR screening. However, our systematic review of the literature reveals few studies studied the impact of different factors on these DL algorithms, that are important for clinical deployment in real-world settings. Using 455,491 retinal images, we evaluated two technical and three image-related factors in detection of referable DR. For technical factors, the performances of four DL models (VGGNet, ResNet, DenseNet, Ensemble) and two computational frameworks (Caffe, TensorFlow) were evaluated while for image-related factors, we evaluated image compression levels (reducing image size, 350, 300, 250, 200, 150 KB), number of fields (7-field, 2-field, 1-field) and media clarity (pseudophakic vs phakic). In detection of referable DR, four DL models showed comparable diagnostic performance (AUC 0.936-0.944). To develop the VGGNet model, two computational frameworks had similar AUC (0.936). The DL performance dropped when image size decreased below 250 KB (AUC 0.936, 0.900, p < 0.001). The DL performance performed better when there were increased number of fields (dataset 1: 2-field vs 1-field-AUC 0.936 vs 0.908, p < 0.001; dataset 2: 7-field vs 2-field vs 1-field, AUC 0.949 vs 0.911 vs 0.895). DL performed better in the pseudophakic than phakic eyes (AUC 0.918 vs 0.833, p < 0.001). Various image-related factors play more significant roles than technical factors in determining the diagnostic performance, suggesting the importance of having robust training and testing datasets for DL training and deployment in the real-world settings.

TAVI for Pure Native Aortic Regurgitation: Are We There Yet?

Treatment of degenerative aortic stenosis has been transformed by transcatheter aortic valve implantation (TAVI) over the past 10-15 years. The success of various technologies has led operators to attempt to broaden the indications, and many patients with native valve aortic regurgitation have been treated 'off label' with similar techniques. However, the alterations in the structure of the valve complex in pure native aortic regurgitation are distinct to those in degenerative aortic stenosis, and there are unique challenges to be overcome by percutaneous valves. Nevertheless some promise has been shown with both non-dedicated and dedicated devices. In this article, the authors explore some of these challenges and review the current evidence base for TAVI for aortic regurgitation.

Defining a 'frequent admitter' phenotype among patients with repeat heart failure admissions.

AIMS: We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS: We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (< 2 HF admissions in the index year; n = 7776) (all P < 0.001). Despite similar rates of advanced care utilization, frequent admitters had longer length of stay (median 4.3 vs. 4.0 days), higher annual inpatient costs (€ 7015 vs. € 2967) and higher all-cause mortality at 3 years compared to the non-frequent admitters (adjusted odds ratio 2.33, 95% confidence interval 2.11-2.58; P < 0.001). CONCLUSION: 'Frequent admitters' have distinct clinical characteristics and worse outcomes compared to non-frequent admitters. This study may provide a means of anticipating the HF readmission burden and thereby aid in healthcare resource distribution relative to the HF admission frequency phenotype.

Deep learning in estimating prevalence and systemic risk factors for diabetic retinopathy: a multi-ethnic study.

In any community, the key to understanding the burden of a specific condition is to conduct an epidemiological study. The deep learning system (DLS) recently showed promising diagnostic performance for diabetic retinopathy (DR). This study aims to use DLS as the grading tool, instead of human assessors, to determine the prevalence and the systemic cardiovascular risk factors for DR on fundus photographs, in patients with diabetes. This is a multi-ethnic (5 races), multi-site (8 datasets from Singapore, USA, Hong Kong, China and Australia), cross-sectional study involving 18,912 patients (n = 93,293 images). We compared these results and the time taken for DR assessment by DLS versus 17 human assessors - 10 retinal specialists/ophthalmologists and 7 professional graders). The estimation of DR prevalence between DLS and human assessors is comparable for any DR, referable DR and vision-threatening DR (VTDR) (Human assessors: 15.9, 6.5% and 4.1%; DLS: 16.1%, 6.4%, 3.7%). Both assessment methods identified similar risk factors (with comparable AUCs), including younger age, longer diabetes duration, increased HbA1c and systolic blood pressure, for any DR, referable DR and VTDR (p > 0.05). The total time taken for DLS to evaluate DR from 93,293 fundus photographs was ~1 month compared to 2 years for human assessors. In conclusion, the prevalence and systemic risk factors for DR in multi-ethnic population could be determined accurately using a DLS, in significantly less time than human assessors. This study highlights the potential use of AI for future epidemiology or clinical trials for DR grading in the global communities.

Artificial intelligence using deep learning to screen for referable and vision-threatening diabetic retinopathy in Africa: a clinical validation study.

BACKGROUND: Radical measures are required to identify and reduce blindness due to diabetes to achieve the Sustainable Development Goals by 2030. Therefore, we evaluated the accuracy of an artificial intelligence (AI) model using deep learning in a population-based diabetic retinopathy screening programme in Zambia, a lower-middle-income country. METHODS: We adopted an ensemble AI model consisting of a combination of two convolutional neural networks (an adapted VGGNet architecture and a residual neural network architecture) for classifying retinal colour fundus images. We trained our model on 76 370 retinal fundus images from 13 099 patients with diabetes who had participated in the Singapore Integrated Diabetic Retinopathy Program, between 2010 and 2013, which has been published previously. In this clinical validation study, we included all patients with a diagnosis of diabetes that attended a mobile screening unit in five urban centres in the Copperbelt province of Zambia from Feb 1 to June 31, 2012. In our model, referable diabetic retinopathy was defined as moderate non-proliferative diabetic retinopathy or worse, diabetic macular oedema, and ungradable images. Vision-threatening diabetic retinopathy comprised severe non-proliferative and proliferative diabetic retinopathy. We calculated the area under the curve (AUC), sensitivity, and specificity for referable diabetic retinopathy, and sensitivities of vision-threatening diabetic retinopathy and diabetic macular oedema compared with the grading by retinal specialists. We did a multivariate analysis for systemic risk factors and referable diabetic retinopathy between AI and human graders. FINDINGS: A total of 4504 retinal fundus images from 3093 eyes of 1574 Zambians with diabetes were prospectively recruited. Referable diabetic retinopathy was found in 697 (22·5%) eyes, vision-threatening diabetic retinopathy in 171 (5·5%) eyes, and diabetic macular oedema in 249 (8·1%) eyes. The AUC of the AI system for referable diabetic retinopathy was 0·973 (95% CI 0·969-0·978), with corresponding sensitivity of 92·25% (90·10-94·12) and specificity of 89·04% (87·85-90·28). Vision-threatening diabetic retinopathy sensitivity was 99·42% (99·15-99·68) and diabetic macular oedema sensitivity was 97·19% (96·61-97·77). The AI model and human graders showed similar outcomes in referable diabetic retinopathy prevalence detection and systemic risk factors associations. Both the AI model and human graders identified longer duration of diabetes, higher level of glycated haemoglobin, and increased systolic blood pressure as risk factors associated with referable diabetic retinopathy. INTERPRETATION: An AI system shows clinically acceptable performance in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, and diabetic macular oedema in population-based diabetic retinopathy screening. This shows the potential application and adoption of such AI technology in an under-resourced African population to reduce the incidence of preventable blindness, even when the model is trained in a different population. FUNDING: National Medical Research Council Health Service Research Grant, Large Collaborative Grant, Ministry of Health, Singapore; the SingHealth Foundation; and the Tanoto Foundation.

Vagus nerve stimulation for the treatment of refractory epilepsy in the CDKL5 Deficiency Disorder.

BACKGROUND: Variants within the CDKL5 gene result in a severe epileptic encephalopathy now known as the CDKL5 Deficiency Disorder. Phenotypic characteristics include global developmental delay and early seizure onset with poor response to anti-epileptic medications. Vagus nerve stimulation (VNS) has been used in other populations as an adjunct treatment for refractory epilepsy with seizure reduction reported in over half of patients. This study aimed to investigate the role of VNS in the CDKL5 Deficiency Disorder. METHODS: The International CDKL5 Disorder Database collects information on individuals with the CDKL5 Deficiency Disorder. Families provide information regarding seizure characteristics and their pharmaceutical and non-pharmaceutical management including VNS use. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided from patients attending the CDKL5 Center of Excellence at Children's Hospital Colorado. RESULTS: Individuals who had a pathogenic CDKL5 variant and on whom information regarding VNS treatment was available were identified (n = 222). Previous or current use of VNS was reported for 38 (17.1%), with a median age at implantation of 4.9 years. Improvements in seizure control were reported in over two-thirds (25/36, 69%); including reduction in frequency (17/25, 68%), duration (18/25, 72%) and intensity (15/25, 60%) of seizures. Median duration of VNS use before any seizure improvement was 73 days. Behavioural changes such as improved mood and alertness were reported in nine individuals. Early termination of VNS secondary to side effects was reported in three cases. There was no reduction in number of AEDs for those with VNS treatment. CONCLUSION: Our study suggests that VNS is a generally safe and effective adjunct treatment for CDKL5-associated epilepsy. Additional benefits such as mood and behavioural improvements provide further support of its use in the CDKL5 Deficiency Disorder. Future studies are required to determine the optimal settings and therapeutic potential for this treatment.

Percutaneous extraction of an embolized progesterone contraceptive implant from the pulmonary artery.

The Nexplanon® implant is a commonly used radiopaque contraceptive device that contains progestogen associated with an ethylene vinyl-acetate copolymer resulting in a slow release of the active hormonal ingredient. It is inserted into the subdermal connective tissue and provides contraceptive efficacy for up to 3 years. Device removal for clinical, personal or device "end-of-life span" reasons is straightforward. In rare cases, implant migration can occur locally within centimeters of the insertion site. Distant device embolization is extremely rare and can result in complications including chest pain, dyspnoea, pneumothorax and thrombosis or prevent conception until the active ingredient is depleted. We present one such case, where a Nexplanon® implant embolized into the pulmonary artery of a young female patient. We describe the initial "missed" diagnosis of embolized device on a chest radiograph and subsequent successful percutaneous removal once distant embolization was diagnosed.

Spiral wave attachment to millimeter-sized obstacles.

BACKGROUND: Functional reentry in the heart takes the form of spiral waves. Drifting spiral waves can become pinned to anatomic obstacles and thus attain stability and persistence. Lidocaine is an antiarrhythmic agent commonly used to treat ventricular tachycardia clinically. We examined the ability of small obstacles to anchor spiral waves and the effect of lidocaine on their attachment. METHODS AND RESULTS: Spiral waves were electrically induced in confluent monolayers of cultured, neonatal rat cardiomyocytes. Small, circular anatomic obstacles (0.6 to 2.6 mm in diameter) were situated in the center of the monolayers to provide an anchoring site. Eighty reentry episodes consisting of at least 4 revolutions were studied. In 36 episodes, the spiral wave attached to the obstacle and became stationary and sustained, with a shorter reentry cycle length and higher rate. Spiral waves could attach to obstacles as small as 0.6 mm, with a likelihood for attachment that increased with obstacle size. After attachment, both conduction velocity of the wave-front tip and wavelength near the obstacle adapted from their pre-reentry values and increased linearly with obstacle size. In contrast, reentry cycle length did not correlate significantly with obstacle size. Addition of lidocaine 90 mumol/L depressed conduction velocity, increased reentry cycle length, and caused attached spiral waves to become quasi- attached to the obstacle or terminate. CONCLUSIONS: Anchored spiral waves exhibit properties of both unattached spiral waves and anatomic reentry. Their behavior may be representative of functional reentry dynamics in cardiac tissue, particularly in the setting of monomorphic tachyarrhythmias.

Transaortic transcatheter aortic valve implantation using the Lotus valve: first-in-man experience.

AIMS: To demonstrate the feasibility of implanting the Lotus second-generation transcatheter heart valve (THV) (designed for a transfemoral procedure) via a transaortic approach. METHODS AND RESULTS: We describe a case with severe aortic stenosis in the presence of small calibre and calcified femoral access and severe chronic obstructive pulmonary disease. The transaortic approach was the ideal approach for this patient and we successfully implanted a 25 mm Lotus valve without any complication. CONCLUSIONS: The transaortic access is a feasible and safe alternative in patients who have suboptimal iliofemoral conduits and who will benefit from the unique features of the Lotus THV.

Transcatheter Aortic Valve Implantation Without General Anaesthetic.

Transcatheter aortic valve implantation (TAVI) procedures are increasingly being performed under local anaesthetic, generally with sedation. Operators hope this will reduce mortality, morbidity and length of hospital stay. A general anaesthetic (GA), however, although involving intrinsic risk, permits transoesophageal echocardiogram (TOE) imaging throughout a procedure as well as eliminating patient anxiety, pain and movement. This article reviews the published literature, all single-centre experiences, comparing TAVI procedures performed with and without a GA. Procedures performed without GA are generally shorter with reduced length of stay compared with those performed under GA. There is no evidence of any difference in outcomes.

Single coronary artery presenting as angina.

The authors present an unusual case of chest pain in an 84-year-old Caucasian woman.