Search

Abstract Introduction Mandibular advancement devices (MADs) increase the airway by providing a stable anterior position of the mandible, advancing the tongue and soft palate and potentially changing the genioglossus muscle activity. As such they are an accepted non-surgical treatment option for obstructive sleep apnea (OSA). The study aimed to investigate whether the amount of mandibular advancement impacts treatment outcomes of OSA. Secondary aims included identifying variables correlated with treatment response and assessing changes in polysomnography (PSG) parameters based on advancement. Methods This retrospective study included patients aged ≥ 18 years diagnosed with OSA and treated with MADs. Data were collected from clinical notes, pre- and post-treatment PSG sleep studies. Amount of advancement was determined by the final titrated advancement achieved. Patients were grouped according to whether the final amount of advancement was ≤ 8 mm or > 8 mm. Treatment responses were classified as complete (symptom resolution and RDI 8 mm advancement, but this difference was not statistically significant. Similarly, changes in RDI, LSAT and T90 were not statistically significant between the two groups. There was statistically significant difference in treatment response between age groups, with younger patients (≤ 50 years) showing better response. Conclusion Effectiveness of MADs in the treatment of OSA does not depend on the final titrated advancement achieved. However, younger patients benefit more from MADs, highlighting age as a critical parameter in treatment responses. Clinical implications There is strong evidence to support the use of MADs as a functional second line treatment option to CPAP, and thus understanding the factors that contribute to positive treatment of OSA is important.

Abstract Head motion during MRI compromises image quality for clinical assessments and research. Active motion reduction strategies are effective but rarely applied due to uncertainty in their value for a given study. The ability to anticipate motion based on group characteristics would aid effective neuroimaging study design. This study compared putative motion indicators for their association to fMRI head motion in a large UK Biobank cohort (n = 40,969, aged 54.9 ± 7.5 years, 53% male). Body Mass Index (BMI; βadj = .050, p

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson’s disease (PD), reducing dyskinesia and time spent in the “OFF” state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the “OFF” state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P less than 0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Abstract Pain catastrophizing is an exaggerated focus on pain sensations. It may be an independent factor influencing pain and functional outcomes of knee arthroplasty. We aimed to evaluate the association between pre-operative pain catastrophizing with pain and function outcomes up to one year after knee arthroplasty. We used data from a cohort study of patients undergoing primary knee arthroplasty (either total or unicompartmental arthroplasty) for knee osteoarthritis. Pain catastrophizing was assessed pre-operatively using the Pain Catastrophizing scale (PCS). Other baseline variables included demographics, body mass index, radiographic severity, anxiety, depression, and knee pain and function assessed using the Western Ontario and McMaster University Index (WOMAC). Patients completed the WOMAC at 6- and 12-months after arthroplasty. WOMAC pain and function scores were converted to interval scale and the association of PCS and changes of WOMAC pain and function were evaluated in generalized linear regression models with adjustment with confounding variables. Of the 1136 patients who underwent arthroplasty (70% female, 84% Chinese, 92% total knee arthroplasty), 1102 and 1089 provided data at 6- and 12-months post-operatively. Mean (± SD) age of patients was 65.9 (± 7.0) years. PCS was associated with a change in WOMAC pain at both 6-months and 12-months (β = − 0.04, 95% confidence interval: − 0.06, − 0.02; P

Abstract Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups—Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.

Abstract Purpose Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. Methods We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. Results Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. Conclusion Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease, primarily affecting the middle-aged to elderly population. Among its nonmotor symptoms, cognitive decline (CD) is a precursor to dementia and represents a critical target for early risk assessment and diagnosis. Accurate CD prediction is crucial for timely intervention and tailored management of at-risk patients. This study used machine learning (ML) techniques to predict the CD risk over five-year in early-stage PD. Methods: Data from the Early Parkinson’s Disease Longitudinal Singapore (2014 to 2018) was used to predict CD defined as a one-unit annual decrease or a one-unit decline in Montreal Cognitive Assessment over two consecutive years. Four ML methods—AutoScore, Random Forest, K-Nearest Neighbors and Neural Network—were applied using baseline demographics, clinical assessments and blood biomarkers. Results: Variable selection identified key predictors of CD, including education year, diastolic lying blood pressure, diastolic standing blood pressure, systolic lying blood pressure, Hoehn and Yahr scale, body mass index, phosphorylated tau at threonine 181, total tau, Neurofilament light chain and suppression of tumorigenicity 2. Random Forest was the most effective, achieving an AUC of 0.93 (95% CI: 0.89, 0.97), using 10-fold cross-validation. Conclusions: Here, we demonstrate that ML-based models can identify early-stage PD patients at high risk for CD, supporting targeted interventions and improved PD management.

Neuropsychological assessments play a vital role in the early detection of cognitive disorders. However, the lack of Singapore-specific norms has resulted in a reliance on international, usually Western, norms that potentially reduce the accuracy and reliability of assessments due to sociocultural differences.1 Moreover, the lack of longitudinal norms limits the reliable monitoring of cognitive changes over time.

Abstract There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5–11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p

Introduction: Patients with cancer are known to have an increased risk of ischemic stroke (IS) around the time of their diagnosis. However, there is a paucity of data in Asian populations, and as such, we aimed to determine cancer incidence rates and patterns in Asian IS patients as well as investigate the differences in vascular risk profile of IS patients with and without concomitant cancer. Methods: We conducted a retrospective cross-sectional study using data from the Singapore Stroke and Cancer registries. We defined cases as patients with IS and a cancer diagnosis 2 years before or after the index IS. Cancer incidence was determined using the same direct age-standardization method performed for the Singapore general population in the 2015 Singapore cancer report. Multivariable logistic regression was used to analyze differences in vascular risk factors. Results: Among 21,068 IS patients (mean age, 67.9 ± 13.3 years), 6.3% (1,330) were found to have concomitant cancer; 4.4% (935) had prior cancer while 1.8% (395) had cancer diagnoses within 2 years following IS. The cancer incidence among IS patients was 3,393 (95% confidence interval [CI], 1,937–4,849) per 100,000 person-years compared to 219–231 per 100,000 person-years in the general population. Older age (odds ratio [OR], 1.02 [95% CI, 1.01–1.02] per year), males (OR, 1.25 [95% CI, 1.11–1.41), Chinese ethnicity (OR, 1.61 [95% CI, 1.37–1.89]) and a lower prevalence of hypertension (OR, 0.84 [95% CI, 0.73–0.97)]), and hyperlipidemia (OR, 0.53 [95% CI, 0.45–0.62]) were independently associated with cancer-related IS. Conclusions: The age-standardized cancer incidence was 15 times higher in IS patients than the general population. IS patients with concomitant cancer were older and had a lower prevalence of vascular risk factors.

Abstract Background Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning–based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes. Methods The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%. Results This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models. Conclusion AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data.

Background: Cognitive assessments for patients with neurocognitive disorders are mostly measured by the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left-skewed and the results of the association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions. Materials and Methods: In this retrospective cohort study of individuals with subjective cognitive decline or mild cognitive impairment, the inverse-transformed cognitive outcomes are modelled using different statistical distributions. The robustness of the proposed models are checked under different scenarios: with intercept-only, models with covariates, and with and without bootstrapping. Results: The main results were based on the VCAT score and validated via the MoCA score. The findings suggested that the inverse transformation method improved the modelling the cognitive scores compared to the conventional methods using the original cognitive scores. The association of the baseline characteristics (age, gender, and years of education) and the cognitive outcomes were reported as estimates and 95% confidence intervals. Bootstrap methods improved the estimate precision and the bootstrapped standard errors of the estimates were more robust. Cognitive outcomes were widely analysed using linear regression models with the default normal distribution as a conventional method. We compared the results of our suggested models with the normal distribution under various scenarios. Goodness-of-fit measurements were compared between the proposed models and conventional methods. Conclusions: The findings support the use of the inverse transformation method to model the cognitive outcomes instead of the original cognitive scores for early-stage neurocognitive disorders where the cognitive outcomes are left-skewed.

Abstract The biological underpinnings of the PD clusters remain unknown as the existing PD clusters lacks biomarker characterization. We try to identify clinical subtypes of Parkinson Disease (PD) in an Asian cohort and characterize them by comparing clinical assessments, genetic status and blood biochemical markers. A total of 206 PD patients were included from a multi-centre Asian cohort. Hierarchical clustering was performed to generate PD subtypes. Clinical and biological characterization of the subtypes were performed by comparing clinical assessments, allelic distributions of Asian related PD gene (SNCA, LRRK2, Park16, ITPKB, SV2C) and blood biochemical markers. Hierarchical clustering method identified three clusters: cluster A (severe subtype in motor, non-motor and cognitive domains), cluster B (intermediate subtype with cognitive impairment and mild non-motor symptoms) and cluster C (mild subtype and young age of onset). The three clusters had significantly different allele frequencies in two SNPs (Park16 rs6679073 A allele carriers in cluster A B C: 67%, 74%, 89%, p = 0.015; SV2C rs246814 T allele distribution: 7%, 12%, 25%, p = 0.026). Serum homocysteine (Hcy) and C-reactive protein (CRP) levels were also significantly different among three clusters (Mean levels of Hcy and CRP among cluster A B C were: 19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6, adjusted p = 0.005; 2.5 ± 5.0, 1.5 ± 2.4, 0.9 ± 2.1, adjusted p

Summary: The AutoScore framework can automatically generate data-driven clinical scores in various clinical applications. Here, we present a protocol for developing clinical scoring systems for binary, survival, and ordinal outcomes using the open-source AutoScore package. We describe steps for package installation, detailed data processing and checking, and variable ranking. We then explain how to iterate through steps for variable selection, score generation, fine-tuning, and evaluation to generate understandable and explainable scoring systems using data-driven evidence and clinical knowledge.For complete details on the use and execution of this protocol, please refer to Xie et al. (2020),1 Xie et al. (2022)2, Saffari et al. (2022)3 and the online tutorial https://nliulab.github.io/AutoScore/. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

IntroductionGiven that reports on severe diazoxide (DZX) toxicity are increasing, we aimed to understand if the short-term clinical outcomes of small-for-gestational-age (SGA) infants with hyperinsulinemic hypoglycemia (HH) managed primarily by supportive care, termed watchful waiting (WW), are different from those treated with DZX.MethodA real-life observational cohort study was conducted from 1 September 2014 to 30 September 2020. The WW or DZX management decision was based on clinical and biochemical criteria. We compared central line duration (CLD), postnatal length of stay (LOS), and total intervention days (TIDs) among SGA-HH infants treated with DZX versus those on a WW approach. Fasting studies determined the resolution of HH.ResultAmong 71,836 live births, 11,493 were SGA, and 51 SGA infants had HH. There were 26 and 25 SGA-HH infants in the DZX and WW groups, respectively. Clinical and biochemical parameters were similar between groups. The median day of DZX initiation was day 10 of life (range 4–32), at a median dose of 4 mg/kg/day (range 3–10). All infants underwent fasting studies. Median CLD [DZX, 15 days (6–27) vs. WW, 14 days (5–31), P = 0.582] and postnatal LOS [DZX, 23 days (11–49) vs. WW, 22 days (8–61), P = 0.915] were comparable. Median TID was >3-fold longer in the DZX than the WW group [62.5 days (9–198) vs. 16 days (6–27), P < 0.001].ConclusionCLD and LOS are comparable between WW and DZX groups. Since fasting studies determine the resolution of HH, physicians should be aware that clinical intervention of DZX-treated SGA-HH patients extends beyond the initial LOS.

Abstract Background As most patients are likely to first interface with their community general practitioner (GP) or geriatrician for chronic healthcare conditions, these non-neurologists practitioners are well-placed to diagnose, initiate treatment in symptomatic Parkinson’s disease (PD) patients, and provide regular and timely management of their PD. However, current studies suggest that the role of the GP and geriatrician in providing holistic care for PD patients may be limited by factors such as patient perceptions, and a lack of knowledge base in the quality measures of care. This paper aims to better understand the different management styles between GPs and geriatricians practicing in public institutions in Singapore, qualify the difficulties they face in providing patient-centric care for PD patients, and identify any gaps in quality measures of care. Methods A questionnaire was completed anonymously by GPs (n = 43) and geriatricians (n = 33) based at public institutions, on a voluntary basis before a compulsory didactic teaching on PD. Questions were modelled after quality measures set out by the American Academy of Neurology, specifically eliciting information on falls, non-motor symptoms, exercise regime and medication-related symptoms. “PD management practices and styles” questions were answered by the respondents on a 4-point Likert scale. Results Geriatricians spent more time in consult with PD patients compared with GPs (median [Q1-Q3] = 20 [15–30] vs 10 [10–15] minutes, p

Abstract Background Southeast Asia represents 10% of the global population, yet little is known about regional clinical characteristics of dementia and risk factors for dementia progression. This study aims to describe the clinico-demographic profiles of dementia in Southeast Asia and investigate the association of onset-type, education, and cerebrovascular disease (CVD) on dementia progression in a real-world clinic setting. Methods In this longitudinal study, participants were consecutive series of 1606 patients with dementia from 2010 to 2019 from a tertiary memory clinic from Singapore. The frequency of dementia subtypes stratified into young-onset (YOD;

Introduction: Detection of atrial fibrillation (AF) is challenging in patients after ischemic stroke due to its paroxysmal nature. We aim to determine the utility of a combined clinical, electrocardiographic and genetic variables model to predict AF in a post-stroke population. Materials and Methods: We performed a cohort study at a single comprehensive stroke centre from 09/11/2009 to 31/10/2017. All patients recruited were diagnosed with acute ischemic stroke or transient ischemic attacks. Electrocardiographic variables including p-wave terminal force (PWTF), corrected QT interval (QTc) and genetic variables including single nucleotide polymorphisms (SNP) at the 4q25 (rs2200733) were evaluated. Clinical, electrocardiographic and genetic variables of patients without AF and those who developed AF were compared. Multiple logistic regression analysis and receiver operating characteristics were performed to identify parameters and determine their ability to predict the occurrence of AF. Results: Out of 709 patients (median age of 59 years, IQR 52-67) recruited, sixty (8.5%) were found to develop AF on follow-up. Age (odds ratio (OR): 3.49, 95% confidence interval (CI): 2.03-5.98, p

AimThis study aims to assess the integrity of white matter in various segments of the corpus callosum in Alzheimer's disease (AD) by using metrics derived from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and white matter tract integrity model (WMTI) and compare these findings to healthy controls (HC).MethodsThe study was approved by the institutional ethics board. 12 AD patients and 12 HC formed the study population. All AD patients were recruited from a tertiary neurology memory clinic. A standardized battery of neuropsychological assessments was administered to the study participants by a trained rater. MRI scans were performed with a Philips Ingenia 3.0T scanner equipped with a 32-channel head coil. The protocol included a T1-weighted sequence, FLAIR and a dMRI acquisition. The dMRI scan included a total of 71 volumes, 8 at b = 0 s/mm2, 15 at b = 1,000 s/mm2 and 48 at b = 2,000 s/mm2. Diffusion data fit was performed using DKI REKINDLE and WMTI models.Results and discussionWe detected changes suggesting demyelination and axonal degeneration throughout the corpus callosum of patients with AD, most prominent in the mid-anterior and mid-posterior segments of CC. Axial kurtosis was the most significantly altered metric, being reduced in AD patients in almost all segments of corpus callosum. Reduced axial kurtosis in the CC segments correlated with poor cognition scores in AD patients in the visuospatial, language and attention domains.

BackgroundSleep disorders are common in Parkinson's disease (PD). However, the longitudinal relationship between sleep quality and the other non-motor symptoms of PD has not been well characterized, especially in early PD.ObjectiveTo explore the value of baseline sleep quality in predicting the progression of other non-motor symptoms in early PD.Methods109 early PD patients were recruited to the study. Patients were stratified into good and poor sleepers using the Pittsburgh Sleep Quality Index (PSQI). Assessments performed at baseline and 1 year follow-up included the Epworth Sleepiness Scale, Fatigue Severity Scale, Non-Motor Symptom Scale, Geriatric Depression Scale, Hospital Anxiety and Depression Scale, Apathy Scale, Montreal Cognitive Assessment and detailed neuropsychological assessments. Multivariable linear regression was performed at baseline to investigate differences in clinical scores between poor and good sleepers, while multivariable regression models were used to investigate associations between sleep quality and progression of test scores at 1 year follow-up.Results59 poor sleepers and 50 good sleepers were identified. At baseline, poor sleepers had greater HADS anxiety scores (p = 0.013) [2.99 (95% CI 2.26, 3.73)] than good sleepers [1.59 (95% CI 0.75, 2.42)]. After 1 year, poor sleepers had greater fatigue (FSS scores +3.60 as compared to −2.93 in good sleepers, p = 0.007) and depression (GDS scores +0.42 as compared to −0.70, p = 0.006).ConclusionThis study shows a longitudinal association between sleep quality, fatigue, and depression in early PD patients, independent of medication effect and disease severity, this may support the hypothesis that a common serotonergic pathway is implicated in these non-motor symptoms.

Abstract Background An important cause of hemisensory syndrome is ischemic stroke. However, the diagnostic yield of neuroradiological imaging on hemisensory syndrome is low. Therefore, we aim to describe patients hospitalized with isolated hemisensory syndrome, and to identify clinical features associated with an aetiology of ischemic stroke. Methods We performed a single centre retrospective observation study, identifying patients who were hospitalised with hemisensory syndrome from October 2015 to March 2016, and whom underwent a magnetic resonance imaging (MRI) brain during the admission. Ischemic stroke was defined as the presence of restricted diffusion-weighted image on the MRI brain. Clinical information was analysed and compared between patients with and without stroke seen on MRI brain. Results 79 patients, 36 (45.6%) males and 43 (54.4%) females, aged between 30 to 87 years (mean 54), were included in the final analysis. 18 (22.8%) patients were identified to have an acute ischemic stroke. Clinical features associated with ischemic stroke in hospitalised patients with hemisensory syndrome include symptom onset of ≤24 h at presentation (odds ratio 31.4, 95% CI 3.89–254.4), advanced age (odds ratio 1.14, CI 1.05–1.25) and smoking (odds ratio 7.35, 95% CI 1.20–45). Conclusion Older patients, with a history of smoking, and who present with an acute onset of symptoms, are more likely to have ischemic stroke as the cause of their hemisensory syndrome.

IntroductionPrimary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA.MethodsWe prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment.ResultsAt baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by −2.3, 95% CI: −3.9 to −0.6, P = 0.010, and post-medications by −1.3, 95% CI: −2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e’ (P = 0.006), whereas it was not statistically significant in patients treated with medications.ConclusionTreatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03174847.

Summary: Background: Return of spontaneous circulation (ROSC) before arrival at the emergency department is an early indicator of successful resuscitation in out-of-hospital cardiac arrest (OHCA). Several ROSC prediction scores have been developed with European cohorts, with unclear applicability in Asian settings. We aimed to develop an interpretable prehospital ROSC (P-ROSC) score for ROSC prediction based on patients with OHCA in Asia. Methods: This retrospective study examined patients who suffered from OHCA between Jan 1, 2009 and Jun 17, 2018 using data recorded in the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. AutoScore, an interpretable machine learning framework, was used to develop P-ROSC. On the same cohort, the P-ROSC was compared with two clinical scores, the RACA and the UB-ROSC. The predictive power was evaluated using the area under the curve (AUC) in the receiver operating characteristic analysis. Findings: 170,678 cases were included, of which 14,104 (8.26%) attained prehospital ROSC. The P-ROSC score identified a new variable, prehospital drug administration, which was not included in the RACA score or the UB-ROSC score. Using only five variables, the P-ROSC score achieved an AUC of 0.806 (95% confidence interval [CI] 0.799–0.814), outperforming both RACA and UB-ROSC with AUCs of 0.773 (95% CI 0.765–0.782) and 0.728 (95% CI 0.718–0.738), respectively. Interpretation: The P-ROSC score is a practical and easily interpreted tool for predicting the probability of prehospital ROSC. Funding: This research received funding from SingHealth Duke-NUS ACP Programme Funding (15/FY2020/P2/06-A79).

BackgroundDecompressive craniectomy (DC) improves the survival and functional outcomes in patients with malignant cerebral infarction. Currently, there are no objective intraoperative markers that indicates adequate decompression. We hypothesise that closure intracranial pressure (ICP) correlates with postoperative outcomes.MethodsThis is a multicentre retrospective review of all 75 DCs performed for malignant cerebral infarction. The patients were divided into inadequate ICP (iICP) and good ICP (gICP) groups based on a suitable ICP threshold determined with tiered receiver operating characteristic and association analysis. Multivariable logistic regression was performed for various postoperative outcomes.ResultsAn ICP threshold of 7 mmHg was determined, with 36 patients (48.0%) and 39 patients (52.0%) in the iICP and gICP group, respectively. After adjustment, postoperative osmotherapy usage was more likely in the iICP group (OR 6.32, p = 0.003), and when given, was given for a longer median duration (iICP, 4 days; gICP, 1 day, p = 0.003). There was no difference in complications amongst both groups. When an ICP threshold of 11 mmHg was applied, there was significant difference in the duration on ventilator (ICP ≥11 mmHg, 3–9 days, ICP

Abstract Background Acute ischemic stroke is a time-sensitive emergency where accurate diagnosis is required promptly. Due to time pressures, stroke mimics who present with similar signs and symptoms as acute ischemic stroke, pose a diagnostic challenge to the emergency physician. With limited access to investigative tools, clinical prediction, tools based only on clinical features, may be useful to identify stroke mimics. We aim to externally validate the performance of 4 stroke mimic prediction scales, and derive a novel decision tree, to improve identification of stroke mimics. Methods We performed a retrospective cross-sectional study at a primary stroke centre, served by a telestroke hub. We included consecutive patients who were administered intravenous thrombolysis for suspected acute ischemic stroke from January 2015 to October 2017. Four stroke mimic prediction tools (FABS, simplified FABS, Telestroke Mimic Score and Khan Score) were rated simultaneously, using only clinical information prior to administration of thrombolysis. The final diagnosis was ascertained by an independent stroke neurologist. Area under receiver operating curve (AUROC) analysis was performed. A classification tree analysis was also conducted using variables which were found to be significant in the univariate analysis. Results Telestroke Mimic Score had the highest discrimination for stroke mimics among the 4 scores tested (AUROC = 0.75, 95% CI = 0.63–0.87). However, all 4 scores performed similarly (DeLong p > 0.05). Telestroke Mimic Score had the highest sensitivity (91.3%), while Khan score had the highest specificity (88.2%). All 4 scores had high positive predictive value (88.1 to 97.5%) and low negative predictive values (4.7 to 32.3%). A novel decision tree, using only age, presence of migraine and psychiatric history, had a higher prediction performance (AUROC = 0.80). Conclusion Four tested stroke mimic prediction scales performed similarly to identify stroke mimics in the emergency setting. A novel decision tree may improve the identification of stroke mimics.

Abstract Background The main motor subtypes of Parkinson’s disease (PD) include tremor-dominant (TD) and postural instability gait disorder (PIGD), with varying disease course that warrant the development of biomarkers capable of predicting progression according to motor subtype. The PIGD subtype is associated with a poorer prognosis, hence identification of a biomarker associated with PIGD is clinically relevant. Neurofilament light (NfL) chain is a potential biomarker of disease severity in neurological disorders including PD. However, no study has investigated NfL and PD motor subtypes. Here, we aimed to investigate the diagnostic and prognostic utility of plasma NfL for PD motor subtypes in early Parkinson’s disease. Given the higher risk for cognitive and motor decline in PIGD, we hypothesized that plasma NfL is a potential biomarker for PIGD. Methods Plasma NfL was measured in 199 participants (149 PD and 50 healthy controls, HC) using an ultrasensitive single molecule array. Patients were classified into TD or PIGD based on MDS-UPDRS components. After 2 years, 115 patients were reassessed. Association between NfL and clinical measures in PIGD and TD at baseline and at 2-year follow-up were analysed. Results At baseline, plasma NfL levels were higher in PD than HC (8.8 ± 3.4 vs 16.2 ± 7.6 pg/ml, p

BackgroundPrimary aldosteronism (PA) is the most common cause of secondary hypertension, and patients are at an increased risk of atrial fibrillation (AF) and stroke. We assessed the prevalence of PA in patients with recent stroke.MethodsWe recruited 300 patients admitted to an acute stroke unit with diagnosis of cerebrovascular accident (haemorrhagic/ischaemic) or transient ischaemic attack. Three months post-stroke, plasma renin and aldosterone were measured. Patients with an elevated aldosterone–renin ratio proceeded to the confirmatory saline loading test.ResultsTwenty-six of 192 (14%) patients had an elevated aldosterone–renin ratio. Three of 14 patients who proceeded to saline loading were confirmed with PA (post-saline aldosterone >138 pmol/l). Another three patients were classified as confirmed/likely PA based on the markedly elevated aldosterone–renin ratio and clinical characteristics. The overall prevalence of PA amongst stroke patients with hypertension was 4.0% (95% confidence interval (CI): 0.9%–7.1%). Prevalence of PA was higher amongst patients with cardioembolic stroke, 11% (95% CI: 1.3%–33%), resistant hypertension, 11% (95% CI: 0.3%–48%), and hypertension and AF, 30% (95%CI: 6.7%–65%). If only young patients or those with hypokalaemia were screened for PA, half of our patients with PA would not have been diagnosed. Our decision tree identified that stroke patients with AF and diastolic blood pressure ≥83mmHg were most likely to have PA.ConclusionWe found that amongst hypertensive patients with stroke, PA was more prevalent in those with AF, or cardioembolic stroke. Screening for PA should be considered for all patients with stroke.

Summary: Background: Bystander cardiopulmonary resuscitation (BCPR) is a critical component of the 'chain of survival' in reducing mortality among out-of-hospital cardiac arrest (OHCA) victims. Inconsistent findings on gender disparities among adult recipients of layperson BCPR have been reported in the literature. We aimed to fill this knowledge gap by investigating the extent of gender disparities in a cross-national setting within Pan-Asian communities. Methods: We utilised data collected from the Pan-Asian Resuscitation Outcomes Study (PAROS), an international, multicentre, prospective study conducted between 2009 and 2018. We included all OHCA cases with non-traumatic arrest aetiology transported by emergency medical services and excluded study sites that did not consistently collect information about the location of cardiac arrest. Logistic regression was used to analyse the association between gender and BCPR, stratified by location. Findings: We analysed a cohort of 56,192 OHCA cases with an overall BCPR rate of 36.2% (20,329/56,192). At public locations, the BCPR rate was 31.2% (631/2022) for female and 36.4% (3235/8892) for male OHCA victims; while at home, the rate was 38.3% (6838/17,842) for females and 35.1% (9625/27,436) for males. Controlling for site differences and several factors in multivariable logistic regression, we found females less likely to receive BCPR than males in public locations (odds ratio [OR]=0.89, 95% confidence interval [CI]: 0.70–0.99), but more likely to receive BCPR at home (OR=1.16, 95% CI: 1.11–1.21). Interpretation: In Pan-Asian communities, gender differences exist in adult recipients of BCPR and differ between home and public locations. Future studies should account for additional information on bystanders and societal factors to identify targets for interventions. Funding: The study was supported by grants from the National Medical Research Council (NMRC/CSA/0049/2013) and Laerdal Foundation (20040).

Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number variations (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, to study the relationship between individual genomic aberrations and therapeutic susceptibilities, we integrated comprehensive genomic profiling of neuroblastoma tumors with drug screening of corresponding PDCs against 418 targeted inhibitors. We quantified the strength of association between copy number and cytotoxicity, and validated significantly correlated gene-drug pairs in public data and using machine learning models. Somatic mutations were infrequent (3.1 per case), but copy number losses in 1p (31%) and 11q (38%), and gains in 17q (69%) were prevalent. Critically, in-vitro cytotoxicity significantly correlated only with CNVs, but not SNVs. Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Predictive Markov random field models constructed from CNVs alone recapitulated the true z-score-weighted associations, with the strongest gene-drug functional interactions in subnetworks involving PI3K and JAK-STAT pathways. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers.

Background: Geospatial distribution analysis is a highly useful tool, especially in the field of health research and health economics. We aimed to study the geospatial distribution of poisoned patients and the risk factors in Mashhad, Iran. Methods: This was a retrospective cross-sectional study of patients treated at the Medical Toxicology Center, Imam Reza Hospital, Mashhad, Iran, which is the only referral center in northeast of Iran, in 2013. Negative binomial and Poisson approach via generalized linear mixed models were performed to investigate the association between socio-demographic characteristics with the number of reported cases of poisoning. Results: A total of 5064 poisoned patients (52% females) were included. Most of the poisoned patients were within the age group of 20-29 years old (41.4%). Pharmaceutical agents were the most common cause of poisonings (64.6%). The local test of spatial autocorrelation (Moran’s I) confirms that the poisoning had cluster pattern in Mashhad. Number of poisoning events were found to be associated with population density (RR= 1.00011; 95% CI 1.0001-1.00013), and the frequency of people with less than high school education (RR=1.49; 95% CI 1.32-1.68). Conclusion: The geospatial factors may have impact on the number of acute poisoning events in a city. Some parts of a city may exhibit spatial clustering in poisoning events. Once clusters are found, interventions can be focused to specific geographic locations and would be helpful for healthcare policymakers to focus on prevention programs.

There have been increasing reports of Guillain–Barré syndrome (GBS), a rare but debilitating neurological disease, occurring post-COVID-19 vaccination. However, the outcomes and relationships between patient demographics and clinical outcomes of post-COVID-19 vaccination GBS remain unclear. To bridge this gap, our study investigates the outcomes and clinical factors associated with poorer GBS outcomes following COVID-19 vaccination. We conducted a review and pooled analysis of detailed data extracted from 57 published cases with the relevant search strategies and criteria. The groups compared included male versus female patients, 1st dose versus 2nd dose and early onset versus late onset of GBS. Multivariate regression analysis was performed to compare the vaccine type, clinical severity and post-treatment outcomes between these groups of patients. Our results highlight for the first time that females were significantly more likely to have severe clinical presentation and poorer outcomes compared to males. Additionally, viral vector vaccines were the predominant vaccine type administered in early-onset post-COVID-19-vaccination GBS and GBS occurring after the 1st vaccination dose. It was also shown that reported cases of post-vaccination GBS generally displayed a positive response to conventional treatment and had favourable post-treatment outcomes. Through this study, we have established important links and provided assuring evidence for treatment response and post-treatment outcomes of GBS occurring post-COVID-19 vaccination. While the COVID-19 vaccination brings about much greater benefits than risks, our findings provide further impetus for greater vigilance in certain patient groups and more studies to explore the mechanisms behind these links.

Abstract Background Burkholderia pseudomallei is a gram negative bacteria that causes a spectrum of human diseases in the tropics. Although melioidosis is endemic in Southeast Asia, large clinical case series were rarely reported from metropolitan Singapore. Methods This is a retrospective study of 219 consecutive patients with culture proven infections due to Burkholderia pseudomallei between the years 2001 to 2016 managed in Singapore General Hospital (SGH). We aimed to review local patients’ characteristics and identify clinical factors associated with mortality and recurrent melioidosis. Results Culture proven melioidosis occurred in 219 patients, 83.1% were male with a mean age of 55.7 ± 14.3 years and 63.0% had diabetes mellitus. Most patients (71.7%) present within 4 weeks of symptom onset and the most common symptom was fever. The majority of patients had bacteremia (67.6%) and had infection involving the respiratory system (71.2%), presenting most frequently with multi-lobar pneumonia. Thirty-four (15.5%) deaths occurred during the initial hospitalisation with a median time from presentation to death of 6.0 days (interquartile range: 2.8–16.3). Twelve patients demised before the diagnosis of melioidosis was made. Univariate analysis identified patients with symptom duration of longer than 4 weeks, bacteremia, and disease requiring mechanical ventilation, inotropic support or temporary dialysis as factors that were significantly associated with mortality. Having bacteremia and disease requiring mechanical ventilation remained statistically significant factors in the multivariable analysis. Twenty-one (11.4%) patients developed at least 1 episode of culture proven recurrent infection, with 15 recurring within the first 12 months of their initial infection. Eight patients developed more than 1 episode of culture proven recurrent infection. Patients with multifocal infection were more likely to develop recurrent infection. Conclusion In metropolitan Singapore, melioidosis was associated with mortality in excess of 15%, where more than a third occurred before diagnosis. This study reminds local physicians that melioidosis is still a serious infection affecting local male diabetic patients and an important differential diagnosis in a patient presenting with severe multi-lobar pneumonia and septic shock. Recurrent infections occurred in 11.4% and the weight-based dosing of oral eradication antibiotics may improve the management of this disease locally.