Site and Burden of Lower Limb Atherosclerosis Predicts Long-term Mortality in a Cohort of Patients With Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Lower limb peripheral arterial disease (PAD) is becoming increasingly common. Lower limb perfusion, as determined by the ankle brachial pressure index (ABPI), is a recognised predictor of overall mortality. The increasing role of non-invasive imaging in patient assessment may aid in the ability to predict poor patient outcomes. METHODS: This study included all patients undergoing a lower limb arterial duplex over a period of 20 months. The site and burden of atherosclerosis within the lower limb was determined using the well validated Bollinger score. Patient demographic data were also collated. The primary outcome measure was all cause mortality. RESULTS: A total of 678 patients were included (median age 74 years). The overall median follow up period was 69.9 months. Of these, 307 patients reached the primary end point, which was death. Independent predictors of all cause mortality included total Bollinger score (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18 [p < .001]; OR per 10 points), femoropopliteal Bollinger score (OR 1.34, 95% CI 1.11-1.08 [p = .05]; OR per 10 points), and crural Bollinger score (OR 1.03, 95% CI 1.01-1.03 [p = .03]). There was also a significant association between mortality and age, a prior history of ischaemic heart disease, a history of congestive cardiac failure and chronic renal failure (chronic kidney disease ≥ 3). Statin and antiplatelet therapy were protective. CONCLUSION: This contemporary study confirms poor long-term outcomes still exist in patients with PAD. The site and severity of lower limb atherosclerosis are independent predictors of long-term mortality.

A Review of the Efficacy and Role of the Card Sort Exercise in the Treatment of Bipolar Disorder.

The current card sort exercise described by Agius et al. in 2006 provides a tool for patients and their families to characterise the temporal pattern of occurrence of both stereotyped and idiosyncratic prodromal symptoms that serve as early warning signs predicting a relapse. This 'individual relapse signature' is highly specific for bipolar relapse, and aids identification of a relapse such that patients can be channeled into appropriate early intervention pathways. This review examines the role of the card sort exercise in the treatment of bipolar disorder, and evaluates the evidence for its efficacy. Few studies involve the card sort exercise, and those that do paired it with other early therapeutic interventions, such that it was difficult to assess the true contribution of the card sort exercise alone to outcome measures such as time-to-relapse or hospitalisation avoidance. We went back to first principles and evaluated the literature concerning various factors necessary for the card sort exercise to be useful. We concluded that there is good evidence that replicable relapse signatures exist as early warning signs for bipolar relapse, and that a certain subgroup of patients and their families can reliably use these signs to seek help and activate therapeutic interventions to abort the relapse episode. Early intervention is both possible and efficacious, which makes early identification of relapse yet more important. The card sort is of less use for depressive relapses, where prodromal symptoms are harder to pinpoint. The card sort exercise is useful in elucidating the relapse signature for each patient, which can then be used in psychoeducation or identification of future relapse episodes. However, more research is needed directly assessing the usefulness of the card sort exercise in helping patients and their families gain insight into the possibility of an imminent relapse.

Deep Learning Model and its Application for the Diagnosis of Exudative Pharyngitis.

OBJECTIVES: Telemedicine is firmly established in the healthcare landscape of many countries. Acute respiratory infections are the most common reason for telemedicine consultations. A throat examination is important for diagnosing bacterial pharyngitis, but this is challenging for doctors during a telemedicine consultation. A solution could be for patients to upload images of their throat to a web application. This study aimed to develop a deep learning model for the automated diagnosis of exudative pharyngitis. Thereafter, the model will be deployed online. METHODS: We used 343 throat images (139 with exudative pharyngitis and 204 without pharyngitis) in the study. ImageDataGenerator was used to augment the training data. The convolutional neural network models of MobileNetV3, ResNet50, and EfficientNetB0 were implemented to train the dataset, with hyperparameter tuning. RESULTS: All three models were trained successfully; with successive epochs, the loss and training loss decreased, and accuracy and training accuracy increased. The EfficientNetB0 model achieved the highest accuracy (95.5%), compared to MobileNetV3 (82.1%) and ResNet50 (88.1%). The EfficientNetB0 model also achieved high precision (1.00), recall (0.89) and F1-score (0.94). CONCLUSIONS: We trained a deep learning model based on EfficientNetB0 that can diagnose exudative pharyngitis. Our model was able to achieve the highest accuracy, at 95.5%, out of all previous studies that used machine learning for the diagnosis of exudative pharyngitis. We have deployed the model on a web application that can be used to augment the doctor's diagnosis of exudative pharyngitis.

Role of anticoagulation in non-ST-elevation myocardial infarction: a contemporary narrative review.

INTRODUCTION: Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies. In the acute setting, the rationale for their use is to antagonize the ongoing clotting cascade including during percutaneous coronary intervention. Anticoagulation may be an important part of the longer-term antithrombotic strategy especially in patients who have other existing indications (e.g. atrial fibrillation) for their use. AREAS COVERED: In this narrative review, the authors provide a contemporary summary of the anticoagulation strategies of patients presenting with NSTEMI, both in terms of anticoagulation during the acute phase as well as suggested antithrombotic regimens for patients who require long-term anticoagulation for other indications. EXPERT OPINION: Patients presenting with non-ST-elevation myocardial infarction (NSTEMI) should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention. Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter.

Identifying and Solving Gaps in Pre- and In-Hospital Acute Myocardial Infarction Care in Asia-Pacific Countries.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality in the Asia-Pacific region, and mortality rates differ between countries in the region. Systems of care have been shown to play a major role in determining AMI outcomes, and this review aims to highlight pre-hospital and in-hospital system deficiencies and suggest possible improvements to enhance quality of care, focusing on Korea, Japan, Singapore and Malaysia as representative countries. Time to first medical contact can be shortened by improving patient awareness of AMI symptoms and the need to activate emergency medical services (EMS), as well as by developing robust, well-coordinated and centralized EMS systems. Additionally, performing and transmitting pre-hospital electrocardiograms, algorithmically identifying patients with high risk AMI and developing hospital networks that appropriately divert such patients to percutaneous coronary intervention-capable hospitals have been shown to be beneficial. Within the hospital environment, developing and following clinical practice guidelines ensures that treatment plans can be standardised, whilst integrated care pathways can aid in coordinating care within the healthcare institution and can guide care even after discharge. Prescription of guideline directed medical therapy for secondary prevention and patient compliance to medications can be further optimised. Finally, the authors advocate for the establishment of more regional, national and international AMI registries for the formal collection of data to facilitate audit and clinical improvement.

Automated labelling of radiology reports using natural language processing: Comparison of traditional and newer methods.

Automated labelling of radiology reports using natural language processing allows for the labelling of ground truth for large datasets of radiological studies that are required for training of computer vision models. This paper explains the necessary data preprocessing steps, reviews the main methods for automated labelling and compares their performance. There are four main methods of automated labelling, namely: (1) rules-based text-matching algorithms, (2) conventional machine learning models, (3) neural network models and (4) Bidirectional Encoder Representations from Transformers (BERT) models. Rules-based labellers perform a brute force search against manually curated keywords and are able to achieve high F1 scores. However, they require proper handling of negative words. Machine learning models require preprocessing that involves tokenization and vectorization of text into numerical vectors. Multilabel classification approaches are required in labelling radiology reports and conventional models can achieve good performance if they have large enough training sets. Deep learning models make use of connected neural networks, often a long short-term memory network, and are similarly able to achieve good performance if trained on a large data set. BERT is a transformer-based model that utilizes attention. Pretrained BERT models only require fine-tuning with small data sets. In particular, domain-specific BERT models can achieve superior performance compared with the other methods for automated labelling.

Comparative overview of ST-elevation myocardial infarction epidemiology, demographics, management, and outcomes in five Asia-Pacific countries: a meta-analysis.

The aim of this study is to gain insight into the differences in demographics of ST-elevation myocardial infarction (STEMI) patients in Asia-Pacific, as well as inter-country variation in treatment and mortality outcomes. Systematic review of published studies and reports from known registries in Australia, Japan, Korea, Singapore, and Malaysia that began data collection after the year 2000. Supplementary self-report survey questionnaire on public health data answered by representative cardiologists working in these countries. Twenty studies comprising of 158 420 patients were included in the meta-analysis. The mean age was 61.6 years. Chronic kidney disease prevalence was higher in Japan, while dyslipidaemia was low in Korea. Use of aspirin, P2Y12 inhibitors, and statins were high throughout, but ACEi/ARB and ß-blocker prescriptions were lower in Japan and Malaysia. Reperfusion strategies varied greatly, with high rates of primary percutaneous coronary intervention (pPCI) in Korea (91.6%), whilst Malaysia relies far more on fibrinolysis (72.6%) than pPCI (9.6%). Similarly, mortality differed, with 1-year mortality from STEMI was considerably greater in Malaysia (17.9%) and Singapore (11.2%) than in Korea (8.1%), Australia (7.8%), and Japan (6.2%). The countries were broadly similar in development and public health indices. Singapore has the highest gross national income and total healthcare expenditure per capita, whilst Malaysia has the lowest. Primary PCI is available in all countries 24/7/365. Despite broadly comparable public health systems, differences exist in patient profile, in-hospital treatment, and mortality outcomes in these five countries. Our study reveals areas for improvements. The authors advocate further registry-based multi-country comparative studies focused on the Asia-Pacific region.

Hepatic encephalopathy: a rare cause of focal seizures in chronic liver disease.

Hepatic encephalopathy (HE) is an extremely rare cause of focal seizures and is usually a diagnosis of exclusion when more commoner causes such as infection, autoimmune and malignancy have been discounted. The literature reports patients with generalised cerebral oedema and rarely status epilepticus, but these are often in the context of acute liver failure as opposed to chronic liver disease. Here we discuss a case of HE leading to focal neurological deficits and seizures in a 48-year-old woman with a background of chronic alcoholic liver disease. MRI scan showed extensive left-sided tempo-parietal-occipital cortical oedema and electroencephalogram showed widespread moderate HE with runs of epileptiform discharges. The treatment involves antiepileptic therapy as well as standard management of HE with laxatives, rifaximin and optimisation of nutrition.

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).

OBJECTIVES: The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS: This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS: Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS: A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Plasma glucose concentration 60 min post oral glucose load and risk of type 2 diabetes and cardiovascular disease: Pathophysiological implications.

AIM: The aim of this study was to gain insight into the pathophysiological significance of elevated plasma glucose concentrations (mmol/L) 60 min post oral glucose load in apparently healthy individuals. METHODS: Comparison of resistance to insulin action and associated cardio-metabolic risk factors in 490 apparently healthy persons, subdivided into those with a plasma glucose concentration 60 min following a 75-g oral glucose challenge of <8.6 versus ⩾8.6. RESULTS: Insulin resistance was significantly greater in persons with normal glucose tolerance whose 60-min glucose concentration was ⩾8.6, associated with higher blood pressure, plasma concentrations of glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol concentrations. Similar differences were seen in persons with impaired fasting glucose, but not in those with impaired glucose tolerance or both impaired fasting glucose and impaired glucose tolerance. The group whose 60-min glucose was <8.6 (n = 318) contained primarily persons with normal glucose tolerance (88%), whereas the majority of those whose 60-min value was ⩾8.6 (n = 172) had prediabetes (59%) and in particular combined impaired fasting glucose and impaired glucose tolerance. CONCLUSION: Plasma glucose concentration of ⩾8.6 mmol/L 60 min post oral glucose identifies higher proportions of combined impaired fasting glucose and impaired glucose tolerance individuals as well as normal glucose tolerance and impaired fasting glucose individuals with a more adverse cardio-metabolic profile, contributing to observed increased overall risk of type 2 diabetes and other metabolic diseases.

Case report: photo-onycholysis after PUVA treatment for hypopigmented mycosis fungoides with response to topical steroid.

Melanin in the nail bed in patients with skin type VI has been suggested to afford some protection against photo-onycholysis. We report a case of a 16-year-old male patient with skin type VI with onycholysis following PUVA treatment for hypopigmented mycosis fungoides. Symptoms resolved with the application of topical steroid.

Evaluating the impact of Brexit on the pharmaceutical industry.

INTRODUCTION: The UK Pharmaceutical Industry is arguably one of the most important industries to consider in the negotiations following the Brexit vote. Providing tens of thousands of jobs and billions in tax revenue and research investment, the importance of this industry cannot be understated. At stake is the global leadership in the sector, which produces some of the field's most influential basic science and translation work. However, interruptions and losses may occur at multiple levels, affecting patients, researchers, universities, companies and government. GOALS: By understanding the current state of pharmaceutical sector, the potential effect of leaving the European Union (EU) on this successful industry can be better understood. This paper aims to address the priorities for negotiations by collating the analyses of professionals in the field, leading companies and non-EU member states. RESEARCH METHODS: A government healthcare policy advisor and Chief Science Officer (CSO) for a major pharmaceutical firm were consulted to scope the paper. In these discussions, five key areas were identified: contribution, legislative processes, regulatory processes, research and outcomes, commercial risk. Multiple search engines were utilised for selecting relevant material, predominantly PubMed and Google Scholar. To supplement this information, Government documents were located using the "GOV.UK" publications tool, and interviews and commentaries were found through the Google News search function. CONCLUSION: With thorough investigation of the literature, we propose four foundations in the advancement of negotiations. These prioritise: negotiation of 'associated country' status, bilaterally favourable trade agreements, minimal interruption to regulatory bodies and special protection for the movement of workforce in the life sciences industry.