Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

Evaluation of prognostic scores for status epilepticus in the neurology ICU: A retrospective study.

OBJECTIVE: Status epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU. METHODS: Neurology ICU patients with SE requiring continuous electroencephalography (cEEG) monitoring over a 10 year period were included. The STESS, EMSE-EACE and END-IT scores were applied retrospectively. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory value of the scores for inpatient mortality and functional decline, as measured by increase in the modified Rankin Scale (mRS) on discharge. RESULTS: Eighty-five patients were included in the study, of which 71 (83.5%) had refractory SE. Inpatient mortality was 36.5%. Sixty - seven (78.8%) of patients suffered functional decline, with a median mRS of 5 upon hospital discharge. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with inpatient mortality were 0.723 (95% CI 0.613-0.833), 0.722 (95% CI 0.609-0.834) and 0.560 (95% CI 0.436-0.684) respectively. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with functional decline were 0.604 (95% CI 0.468-0.741), 0.596 (95% CI 0.439-0.754) and 0.477 (95% CI 0.331-0.623). SIGNIFICANCE: SE was associated with high mortality and morbidity in this cohort of neurology ICU patients requiring cEEG monitoring. The STESS and EMSE-EACE scores had acceptable AUCs for prediction of inpatient mortality. However, the STESS, EMSE-EACE and END-IT were poorly-correlated with discharge functional outcomes. Further refinements of the scores may be necessary among neurology ICU patients for predicting discharge functional outcomes.

Modelling the Distribution of Cognitive Outcomes for Early-Stage Neurocognitive Disorders: A Model Comparison Approach.

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.

Functional oral status and oral health-related quality of life in community-dwelling older adults in Singapore.

OBJECTIVES: The objectives were to investigate the association between oral functional status (defined by the number of functional teeth and functional occluding units [FOUs]) on oral health-related quality of life (OHRQoL). It also aimed to determine if dentures could compensate for the loss of FOUs in terms of OHRQoL in community-dwelling older adults in Singapore. METHODS: Community-dwelling older adults, aged 60 years and above, were recruited from a community-based oral health functional screening programme from 1 May 2018 to 31 December 2019. During the screening, an Oral Health Impact Profile-14 (OHIP-14) questionnaire and oral examination were administered. Statistical analysis was performed using the chi-square test, univariate logistic regression and multivariate predictive modelling. RESULTS: Data from 1037 participants were analysed (52% female; mean age 71.5 (SD 7.15)). The mean OHIP-14 score was 4.5 ± 7.2. The OHIP-14 scores were significantly associated with the number of functional teeth and the number of FOUs (p < .001). Having at least 20 functional teeth or 10 FOUs was associated with a significantly lower OHIP-14 score. Those with no FOUs had higher OHIP-14 scores compared to those with at least 10 FOUs, even in the presence of a satisfactory denture. CONCLUSION: Maintaining at least 20 functional teeth or 10 FOUs was associated with better OHRQoL among community-dwelling older adults in Singapore. Dentures may have limited compensatory ability in terms of replacing natural functional occlusal units and maintaining OHRQoL.

Recurrent vascular events partially explain association between diabetes and poor prognosis in young ischemic stroke patients.

BACKGROUND AND AIMS: Stroke is the second leading cause of death and third leading cause of disability worldwide. There is an increasing incidence of stroke among the young. In this study, we aimed to identify factors associated with poor long-term prognosis in young stroke patients. METHODS: In this longitudinal observational study, we recruited 147 young ischemic stroke patients within one week of ischemic stroke and followed them up for functional outcome (modified Rankin score (mRS)), recurrent vascular events, and recurrent hospitalisation. Poor function was labelled as mRS score of 3 and above. We performed univariate and multivariable logistic regression analyses to determine factors associated with poor long term functional outcome. RESULTS: At a median follow-up of 7-years, 32 (22%) of the 147 patients had poor functional outcome. In multivariable analyses, diabetes mellitus (OR = 9.01, CI 3.15 to 26.92), was the only independent predictor of poor function. In analyses stratified by diabetic status, recurrent vascular events (OR = 4.47, CI 1.40 to 14.28) were associated with poor functional outcome within young diabetic patients but not in non-diabetic patients. CONCLUSIONS: Our findings suggest that diabetes mellitus affects long-term functional outcome in young ischemic stroke and that its effect is mediated partly by recurrent vascular events. DATA ACCESS STATEMENT: Data obtained from Multi-Centre Retinal study (MCRS), Singapore site. Data cannot be made publicly available due to potentially identifiable research participant information.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Recovery of Volitional Motor Control and Overground Walking in Participants With Chronic Clinically Motor Complete Spinal Cord Injury: Restoration of Rehabilitative Function With Epidural Spinal Stimulation (RESTORES) Trial-A Preliminary Study.

Spinal cord injury (SCI) is damage to any part of the spinal cord resulting in paralysis, bowel and/or bladder incontinence, and loss of sensation and other bodily functions. Current treatments for chronic SCI are focused on managing symptoms and preventing further damage to the spinal cord with limited neuro-restorative interventions. Recent research and independent clinical trials of spinal cord stimulation (SCS) or intensive neuro-rehabilitation including neuro-robotics in participants with SCI have suggested potential malleability of the neuronal networks for neurological recovery. We hypothesize that epidural electrical stimulation (EES) delivered via SCS in conjunction with mental imagery practice and robotic neuro-rehabilitation can synergistically improve volitional motor function below the level of injury in participants with chronic clinically motor-complete SCI. In our pilot clinical RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation), we investigate the feasibility of this combined multi-modal approach in restoring volitional motor control and achieving independent overground locomotion in participants with chronic motor complete thoracic SCI. Secondary aims are to assess the safety of this combination therapy including the off-label SCS usage as well as improving functional outcome measures. To our knowledge, this is the first clinical trial that investigates the combined impact of this multi-modal EES and rehabilitation strategy in participants with chronic motor complete SCI. Two participants with chronic motor-complete thoracic SCI were recruited for this pilot trial. Both participants have successfully regained volitional motor control below their level of SCI injury and achieved independent overground walking within a month of post-operative stimulation and rehabilitation. There were no adverse events noted in our trial and there was an improvement in post-operative truncal stability score. Results from this pilot study demonstrates the feasibility of combining EES, mental imagery practice and robotic rehabilitation in improving volitional motor control below level of SCI injury and restoring independent overground walking for participants with chronic motor-complete SCI. Our team believes that this provides very exciting promise in a field currently devoid of disease-modifying therapies.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

INTRODUCTION: Primary Aldosteronism (PA) is a common cause of hypertension. However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with hypertension is characteristic of PA, and is an indication for screening. We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. METHODS: Our study included all PA patients with hypokalemia diagnosed between 2001 to 2022. Delayed diagnosis was defined as duration of hypokalemia of >1 year from first occurrence, to first evaluation by a PA specialist. Patients were reassessed post-adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. RESULTS: Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 (2.4-7.5) years. Patients with delayed diagnosis were older, had longer duration of hypertension, higher pill burden, lower renal function and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidaemia, and less severe hypokalemia (serum potassium >3.0mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%), P<0.05. Sixty of 118 (50.8%) non-delayed, and 39 of 122 (32.0%) patients with delayed diagnosis underwent surgery. CONCLUSION: Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in hypertension guidelines, and efforts to improve awareness of PA amongst primary care physicians are urgently needed.

Non-Hypertensives and Those with Normal Cholesterol Are More Likely to Have Concomitant Cancer amongst Patients with Ischemic Stroke: A Retrospective Cross-Sectional Registry-Based Study.

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.

BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study.

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 < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5-30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.

Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies.

INTRODUCTION: Misdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD). METHODS: We accessed the National Alzheimer's Coordinating Center database from 2005 to December 2022 data freeze and included 111 and 501 prodromal DLB and AD patients respectively. First visit data was analyzed. RESULTS: Clinician-determined memory impairment is common in prodromal DLB (>70%) but associated with higher risk for AD diagnosis (OR 0.355, p = 0.0003). DLB had a higher proportion of non-amnestic mild cognitive impairment (MCI) diagnoses but statistically insignificance in differentiating the two. Inattention (OR 2.273, p = 0.0015), and neuropsychiatric features, such as visual hallucinations (OR 11.98, p < 0.0001), depressed mood (OR1.709, p = 0.0292), apathy (1.824, p = 0.0345), and night/REM sleep behaviors, are associated with DLB diagnosis. Hallucinations are infrequent (7-11%). Motor symptoms, particularly gait disorders (OR 4.570, p < 0.001), falls (OR3.939, p = 0.0003), tremors (OR2.237, p = 0.0154), slowness (OR3.573, p < 0.0001), and parkinsonism signs (OR2.443, p < 0.0001), are common. 32% showed no parkinsonism during initial presentation. Neuropsychological examination revealed less impaired memory and language but impaired executive function in DLB. CONCLUSION: In clinical practice, it is important to note that memory symptoms although being higher risk associated with AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.

Watchful waiting versus pharmacological management of small-for-gestational-age infants with hyperinsulinemic hypoglycemia.

Introduction: Given 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. Method: A 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. Result: Among 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]. Conclusion: CLD 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.

Lobectomy versus gross total resection for glioblastoma multiforme: A systematic review and individual-participant data meta-analysis.

Overall survival (OS)for glioblastoma multiforme (GBM) has a known association with the extent of tumor resection with gross total resection (GTR) typically considered as the upper limit. In certain regions such as the anterior temporal lobe, more extensive resection by means of a lobectomy may be feasible. In our systematic review and meta-analysis, we aimed to compare the outcomes of lobectomy and GTR for GBM. PubMed and Embase were queriedfor studies that compared the outcomes after lobectomy or GTR for GBM. The primary outcomes were OS, progression-free survival (PFS), and Karnofksy Performance Status (KPS) score at the latest follow-up. The secondary outcomes were seizure control at the latest follow-up and complication rates. Meta-analysis for OS and PFS was performed using individual-participant data reconstructed from published Kaplan-Meier curves. Random-effect meta-analysis was performed for KPS. The secondary outcomes were pooled using descriptive statistics. Of the 795 records screened, 6 were included in our study. Meta-analysis revealed that anterior temporal, frontal, or occipital lobectomy was associated with significantly better OS (p < 0.001) and PFS (p < 0.001) than GTR, but not KPS (MD = 6.37; 95% CI=(-13.80, 26.54); p = 0.536). Anterior temporal lobectomy was associated with significantly better seizure control rates than GTR for temporal GBM (OR = 27; 95% CI=(1.4, 515.9); p = 0.002). There was no statistically significant difference in complication rates between anterior temporal, frontal, or occipital lobectomy and GTR. In conclusion, lobectomy was associated with significantly better OS, PFS, and seizure control than GTR for GBM.

Diffuse alveolar haemorrhage in systemic lupus erythematosus: A multicentre retrospective study in Singapore.

OBJECTIVE: Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival outcomes of SLE patients with DAH in Singapore. METHODS: We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups. RESULTS: A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25-54), with a median disease duration of 8.9 months (IQR: 0.13-102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6-46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026). CONCLUSIONS: The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.

Handling missing values in healthcare data: A systematic review of deep learning-based imputation techniques.

OBJECTIVE: The proper handling of missing values is critical to delivering reliable estimates and decisions, especially in high-stakes fields such as clinical research. In response to the increasing diversity and complexity of data, many researchers have developed deep learning (DL)-based imputation techniques. We conducted a systematic review to evaluate the use of these techniques, with a particular focus on the types of data, intending to assist healthcare researchers from various disciplines in dealing with missing data. MATERIALS AND METHODS: We searched five databases (MEDLINE, Web of Science, Embase, CINAHL, and Scopus) for articles published prior to February 8, 2023 that described the use of DL-based models for imputation. We examined selected articles from four perspectives: data types, model backbones (i.e., main architectures), imputation strategies, and comparisons with non-DL-based methods. Based on data types, we created an evidence map to illustrate the adoption of DL models. RESULTS: Out of 1822 articles, a total of 111 were included, of which tabular static data (29%, 32/111) and temporal data (40%, 44/111) were the most frequently investigated. Our findings revealed a discernible pattern in the choice of model backbones and data types, for example, the dominance of autoencoder and recurrent neural networks for tabular temporal data. The discrepancy in imputation strategy usage among data types was also observed. The "integrated" imputation strategy, which solves the imputation task simultaneously with downstream tasks, was most popular for tabular temporal data (52%, 23/44) and multi-modal data (56%, 5/9). Moreover, DL-based imputation methods yielded a higher level of imputation accuracy than non-DL methods in most studies. CONCLUSION: The DL-based imputation models are a family of techniques, with diverse network structures. Their designation in healthcare is usually tailored to data types with different characteristics. Although DL-based imputation models may not be superior to conventional approaches across all datasets, it is highly possible for them to achieve satisfactory results for a particular data type or dataset. There are, however, still issues with regard to portability, interpretability, and fairness associated with current DL-based imputation models.

A universal AutoScore framework to develop interpretable scoring systems for predicting common types of clinical outcomes.

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/.

COVID-19 infection after SARS-CoV-2 mRNA vaccination in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD patients during the Omicron subvariant BA.1/2 wave in Singapore.

BACKGROUND: The SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore. METHODS: This was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination. RESULTS: Two hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy. CONCLUSIONS: The Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.

Usefulness of the Visual Cognitive Assessment Test in Detecting Mild Cognitive Impairment in the Community.

BACKGROUND: A delay in the detection of mild cognitive impairment (MCI) in the community delays the opportunity for early intervention. Accurate tools to detect MCI in the community are lacking. The Visual Cognitive Assessment Test (VCAT) is a visual based cognitive test useful for multilingual populations without the need for translation. OBJECTIVE: Here, we evaluate the usefulness of VCAT in detecting MCI in a community population in Singapore. METHODS: We recruited 301 participants from the community who completed a detailed neuropsychological assessment and 170 of them completed a 3T magnetic resonance imaging (MRI) brain scan. We performed a receiver operating characteristics analysis to test the diagnostic performance of VCAT compared to Montreal Cognitive Assessment (MoCA) in distinguishing MCI from cognitively normal (CN) by measuring area under the curve (AUC). To test for the association of VCAT with structural MRI, we performed a Pearson's correlation analysis for VCAT and MRI variables. RESULTS: We recruited 39 CN and 262 MCI participants from Dementia Research Centre (Singapore). Mean age of the cohort was 63.64, SD = 9.38, mean education years was 13.59, SD = 3.70 and majority were women (55.8%). VCAT was effective in detecting MCI from CN with an AUC of 0.794 (95% CI 0.723-0.865) which was slightly higher than MoCA 0.699 (95% CI 0.621-0.777). Among subjects with MCI, VCAT was associated with medial temporal lobe atrophy (ρ = -0.265, p = 0.001). CONCLUSIONS: The VCAT is useful in detecting MCI in the community in Singapore and may be an effective measure of neurodegeneration.

Corrigendum: Topology of diffusion changes in corpus callosum in Alzheimer's disease: An exploratory case-control study.

[This corrects the article DOI: 10.3389/fneur.2022.1005406.].

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson disease using machine learning.

BACKGROUND AND PURPOSE: A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson disease (PD) have been investigated separately. However, there is as yet no study including all of them to assess variable importance. Shapley variable importance cloud (ShapleyVIC) can robustly assess variable importance while accounting for correlation between variables. Objectives of this study were (i) to prioritize the important variables associated with PD-MCI and (ii) to explore new blood biomarkers related to PD-MCI. METHODS: ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables associated with PD-MCI. Relative risk was used to quantify the association of final associated variables and PD-MCI in the final multivariable log-binomial regression model. RESULTS: Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and eight variables were subsequently selected in the final model, indicating fewer years of education, shorter history of hypertension, higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor score, higher levels of triglyceride (TG) and apolipoprotein A1 (ApoA1), and SNCA rs6826785 noncarrier status were associated with increased risk of PD-MCI (p < 0.05). CONCLUSIONS: Our study highlighted the strong association between TG, ApoA1, SNCA rs6826785, and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interest.