Combining multimodal magnetic resonance brain imaging and machine learning to unravel neurocognitive function in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.

Hospital admission risk stratification of patients with gout presenting to the emergency department.

To characterise gout patients at high risk of hospitalisation and to develop a web-based prognostic model to predict the likelihood of gout-related hospital admissions. This was a retrospective single-centre study of 1417 patients presenting to the emergency department (ED) with a gout flare between 2015 and 2017 with a 1-year look-back period. The dataset was randomly divided, with 80% forming the derivation and the remaining forming the validation cohort. A multivariable logistic regression model was used to determine the likelihood of hospitalisation from a gout flare in the derivation cohort. The coefficients for the variables with statistically significant adjusted odds ratios were used for the development of a web-based hospitalisation risk estimator. The performance of this risk estimator model was assessed via the area under the receiver operating characteristic curve (AUROC), calibration plot, and brier score. Patients who were hospitalised with gout tended to be older, less likely male, more likely to have had a previous hospital stay with an inpatient primary diagnosis of gout, or a previous ED visit for gout, less likely to have been prescribed standby acute gout therapy, and had a significant burden of comorbidities. In the multivariable-adjusted analyses, previous hospitalisation for gout was associated with the highest odds of gout-related admission. Early identification of patients with a high likelihood of gout-related hospitalisation using our web-based validated risk estimator model may assist to target resources to the highest risk individuals, reducing the frequency of gout-related admissions and improving the overall health-related quality of life in the long term. KEY POINTS : • We reported the characteristics of gout patients visiting a tertiary hospital in Singapore. • We developed a web-based prognostic model with non-invasive variables to predict the likelihood of gout-relatedhospital admissions.

Cognitive Dysfunction in Systemic Lupus Erythematosus: Immunopathology, Clinical Manifestations, Neuroimaging and Management.

Cognitive dysfunction (CD) is a common yet often clinically subtle manifestation that considerably impacts the health-related quality of life in patients with systemic lupus erythaematosus (SLE). Given the inconsistencies in CD assessment and challenges in its attribution to SLE, the reported prevalence of CD differs widely, ranging from 3 to 88%. The clinical presentation of CD in SLE is non-specific and may manifest concurrently with overt neuropsychiatric illness such as psychosis or mood disorders or as isolated impairment of attention, working memory, executive dysfunction or processing speed. Despite the lack of standardized and sensitive neuropsychological tests and validated diagnostic biomarkers of CD in SLE, significant progress has been made in identifying pathogenic neural pathways and neuroimaging. Furthermore, several autoantibodies, cytokines, pro-inflammatory mediators and metabolic factors have been implicated in the pathogenesis of CD in SLE. Abrogation of the integrity of the blood-brain barrier (BBB) and ensuing autoantibody-mediated neurotoxicity, complement and microglial activation remains the widely accepted mechanism of SLE-related CD. Although several functional neuroimaging modalities have consistently demonstrated abnormalities that correlate with CD in SLE patients, a consensus remains to be reached as to their clinical utility in diagnosing CD. Given the multifactorial aetiology of CD, a multi-domain interventional approach that addresses the risk factors and disease mechanisms of CD in a concurrent fashion is the favourable therapeutic direction. While cognitive rehabilitation and exercise training remain important, specific pharmacological agents that target microglial activation and maintain the BBB integrity are potential candidates for the treatment of SLE-related CD.

Facilitators and barriers of Hepatitis B screening and vaccination.

BACKGROUND: Hepatitis B virus (HBV) infection is the most common cause of liver disease and liver cancer in Singapore, being endemic despite availability of an efficacious vaccine. OBJECTIVE: To assess the factors associated with HBV screening and vaccination. METHODS: Using mixed methods analysis, focus group discussions were conducted alongside a cross-sectional study amongst 784 Singapore Citizens and Permanent Residents aged 25-69 residing in Housing and Development Board (HDB) flats. RESULTS: Amongst the respondents, 50.6% were screened and 37.8% were vaccinated. The self-reported prevalence of HBV infection was 3.4% and that of HBsAg seropositivity among those screened was 4.3%. Routine health screening was the most common reason cited for screening (32.9%) while doctors' recommendation was the most common reason for vaccination (42.7%). For both screening and vaccination, knowledge and cost were the top facilitators and barriers respectively. Multivariable regression models revealed the most significant predictors for not undergoing screening to be poor knowledge (p < 0.001), the presence of stigma (p = 0.040) and not being employed in a healthcare sector (p = 0.022), while factors associated with not undergoing vaccination are that of having not undergone screening (p < 0.001) and the lack of importance placed on the knowledge of the possibility of HBV being a silent killer (p = 0.006). CONCLUSION: Several facilitators and barriers are seen to regulate health-seeking behaviour towards HBV infection. Public initiatives including education and financial relief targeting specific population groups should be considered to increase the uptake of HBV screening and vaccination.

Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital.

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA. METHODS: This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013. RESULTS: Eight patients aged 9-41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20-75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients. CONCLUSIONS: With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA.