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BACKGROUND The relationship of early catheter-related bloodstream infections (CRBSIs) with perioperative neutropenia and antibiotic prophylaxis is not well established. We sought to evaluate perioperative factors associated with early CRBSIs in newly diagnosed pediatric cancer patients, particularly hematological indices and antibiotic use. METHODS We retrospectively reviewed national registry records of newly diagnosed pediatric cancer patients with port-a-caths inserted using standardized perioperative protocols where only antibiotic use was not regulated. Thirty-day postoperative CRBSI incidence was correlated with preoperative factors using logistic regression and with postoperative blood counts using linear trend analysis. RESULTS Among 243 patients, 17 CRBSIs (7.0%) occurred at median 14 (range, 8-28) postoperative days. Early CRBSIs were significantly associated with cancer type [acute myeloid leukemia and other leukemias (AML/OLs) vs. solid tumors and lymphomas (STLs): odds ratio (OR), 5.09; P = 0.0036; acute lymphoblastic leukemia vs. STL: OR 0.83; P = 0.0446] but not preoperative antibiotics, absolute neutrophil counts and white blood cell counts. Thirty-day postoperative absolute neutrophil counts and white blood cell trends differed significantly between patients with acute lymphoblastic leukemia and STLs (OR 0.83, P < 0.05) and between AML/OLs and STLs (OR 5.09, P < 0.005), with AML/OL patients having the most protracted neutropenia during this period. CONCLUSIONS Contrary to common belief, low preoperative absolute neutrophil counts and lack of preoperative antibiotics were not associated with higher early CRBSI rates. Instead, AML/OL patients, particularly those with prolonged neutropenia during the first 30 postoperative days, were at increased risk. Our findings do not support the use of empirical preoperative antibiotics and instead identify prolonged postoperative neutropenia as a major contributing factor for early CRBSI.

To comprehensively investigate the efficacy of adjunctive probiotics compared to placebo, using conventional and novel treatment outcomes.Three databases (MEDLINE, EMBASE, and CENTRAL) were searched. Outcomes included percent change in the total number of deep sites before and after therapy, change in mean probing pocket depth (mm), percentage patients requiring additional therapy, risk for disease progression, and microbiological and immunological results. Meta-analysis was conducted to evaluate treatment effects wherever appropriate.Ten studies were selected from 818 records. Meta-analysis showed that adjunctive probiotics had no additional benefit for percentage change of the total number of deeper sites (≥5 mm, ≥6 mm, ≥7 mm) before and after therapy. No significant difference was observed for mean probing pocket depth reduction at 3 and 6 months. Statistically significant beneficial odds ratios for need for additional therapy (OR = 0.19, 95% CI [0.07-0.56]) and risk of disease progression (OR = 0.32, 95% CI [0.14-0.73]) were observed with probiotic administration. Immunological rather than microbiological outcomes correlated more consistently with clinical findings. No adverse events were reported.Adjunctive probiotics are safe in systemically healthy individuals and could offer additional patient-level benefits compared to placebo, hence its use can sometimes be justified.

Background: Mild behavioral impairment (MBI) describes persistent behavioral changes in later life as an at-risk state for dementia. While cardiovascular risk factors (CVRFs) are linked to dementia, it is uncertain how CVRFs are associated with MBI. Objective: To determine the prevalence of MBI and its association with CVRFs among cognitively normal (CN) and mild cognitive impairment (MCI) individuals in Singapore. Methods: 172 individuals (79 CN and 93 MCI) completed the MBI-checklist (MBI-C). The prevalence of MBI and MBI-C sub-domain characteristics among CN and MCI were examined. Regression models evaluated the relationships between MBI-C sub-domain scores with CVRFs. Results: The prevalence of MBI and mean MBI-C total score were significantly higher among MCI than CN (34.4%versus 20.3%, p = 0.022 and 7.01 versus 4.12, p = 0.04). The highest and lowest-rated sub-domains among CN and MCI were impulse dyscontrol and abnormal thoughts and perception respectively. Within the MCI cohort, a higher proportion of individuals with diabetes mellitus (DM) had MBI compared to individuals without DM (28.1%versus 10.4%, p = 0.025). The interaction of DM and MCI cohort resulted in significantly higher mean MBI-C total, decreased motivation, emotional dysregulation, impulse dyscontrol, and abnormal thoughts and perception sub-domain scores. Conclusion: The prevalence of MBI is higher among a Singapore cohort compared to Caucasian cohorts. The associations of DM with both the presence and severity of MBI among MCI suggest that DM may be a risk factor for MBI. The optimization of DM may be a potential therapeutic approach to improve clinical outcomes among MCI with MBI.

INTRODUCTION This study aimed to evaluate the LITE (Lifestyle Intervention for TEenagers) group programme, a family-based behavioural lifestyle intervention for overweight and obese adolescents. METHODS We conducted a two-arm randomised controlled trial that recruited overweight and obese adolescents who attended a tertiary care weight management clinic. Participants were randomised to the LITE programme or usual care. The primary outcome assessed was body mass index (BMI) z-score. Secondary outcomes of anthropometric measurements, metabolic profile, parenting and adolescents’ perception of family support were measured at baseline, three months and six months. Feasibility and acceptability of the LITE programme were also evaluated. RESULTS 61 adolescents were enrolled, with 31 in the LITE programme and 30 in usual care. At three months, participants in the programme had a greater reduction in weight (−0.18 ± 2.40 kg vs. 1.48 ± 1.97 kg; p = 0.107), waist circumference (−1.0 ± 3.1 cm vs. 2.4 ± 2.7 cm; p = 0.016), waist-height ratio (−0.01 ± 0.02 vs. 0.01 ± 0.02; p = 0.040) and systolic blood pressure (−3.8 ± 13.7 vs. 5.7 ± 13.1; p = 0.119) compared to the usual care group. There was no significant difference in BMI z-score. At six months, there were significant improvements in adolescents’ perception of family support for eating habits in the LITE group compared to the usual care group. The LITE programme had a good attendance rate of 67.7% and was well received. CONCLUSION The LITE programme showed feasibility and short-term clinical effectiveness in improving some clinical outcomes and improved adolescents’ perception of family support.

Introduction Subjective cognitive complaints (SCC) and affective symptoms are highly prevalent in Parkinson's Disease (PD). In early PD, SCC prevalence and its affective correlates, using recommended Movement Disorders Society (MDS) Level II Criteria to define the underlying cognitive impairment, has not been previously explored. Methods We recruited 121 participants with early PD from two tertiary hospitals in Singapore. The presence of SCC was defined using a Non-Motor Symptoms Scale Domain-5 Score ≥1. Comprehensive neuropsychological testing was conducted with Mild Cognitive Impairment (PD-MCI) defined using recommended MDS Level II Criteria. Affective symptoms were assessed using the Hospital Anxiety Depression Scale (HADS), Geriatric Depression Scale (GDS) and Apathy Scale (AS). Analysis using multivariable linear regression model was performed. Results In our early PD cohort, SCC prevalence independent of underlying cognitive status was 38.8%. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively (р = 0.241). In cognitively normal PD participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety (β = 0.28, 95% CI = 0.09–0.79, p = 0.014), depression (β = 0.31, 95% CI = 0.10–0.59, p = 0.006) and apathy (β = 0.32, 95% CI = 1.15–5.98, p = 0.004). Such an association was not found in cognitively impaired PD participants. Conclusion SCC is highly prevalent even in early PD. Its implications in early PD differ depending on underlying cognitive status. SCC in cognitively impaired participants underestimates the true prevalence of PD-MCI. In contrast, SCC in cognitively normal participants is suggestive of an underlying affective disorder.

Background The year-round respiratory syncytial virus (RSV) circulation in tropical regions leads to different transmission patterns and burden of disease among infants born very preterm. Methods We conducted a retrospective cohort study to estimate the effectiveness of palivizumab in preventing RSV hospitalization at 6 and 12 months after discharge, among infants born at Results A total of 109 infants (26.3%) received palivizumab at discharge, of 415 who were eligible. All patients received ≥4 doses, with 105 infants (96.3%) completing 5 doses. Within 1 year after discharge, there were 35 RSV-associated admissions (3 [2.8%] in the palivizumab vs 32 [10.5%] in the nonpalivizumab group; P = .02). After adjustment for confounders, the effectiveness of palivizumab against RSV hospitalization was estimated to be 90% (95% confidence interval, 10%–99%) up to 6 months after discharge. The median time to RSV hospitalization was shorter in the nonpalivizumab than in the palivizumab group (median [range], 155 [15–358] vs 287 [145–359] days, respectively; P = .11). Five infants (14.3%), all from the nonpalivizumab group, required admission to the intensive care unit. Conclusions In our setting with year-round RSV circulation, palivizumab prophylaxis was effective in reducing RSV hospitalization among high-risk preterm infants of

Chronic subdural haemorrhage (CSDH) is a common neurosurgical entity with complex pathophysiological pathways. The generally favourable surgical outcome may be affected by its associated risks including recurrence rates. We performed a prospective randomized multi-center clinical trial comparing the addition of tranexamic acid (TXA) to standard neurosurgical procedures for patients with symptomatic CSDH. The primary endpoint was CSDH requiring repeat surgery within 6-month post-operatively. Secondary endpoints were comparison of post-operative volumes between the treatment arms and safety evaluation of the dosing regime. 90 patients were analyzed with 49 patients in the observation arm and 41 patients in the TXA arm. The observation arm had five (10.2%) recurrences compared to two (4.8%, p = 0.221) in the TXA arm. Patients in the TXA arm demonstrated a greater reduction of their CSDH volume at 6 weeks follow up (36.6%) compared to the observation arm (23.3%, p = 0.6648). There were no reportable serious adverse events recorded in the observation arm, compared to 4 (9.8%) patients in the TXA arm. The addition of TXA treatment to standard surgical drainage of CSH did not significantly reduce symptomatic post-operative recurrence. Patients in the TXA arm had a delay in the CSDH recurrence with a comparative reduction of residual hematoma volume at the 6-week follow up although the effect was unsustained. Larger randomized trials with dose adjustments should be considered to investigate subgroups of patients that may benefit from this medical adjunct.

Background Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not been fully explored. Objective To describe the frequency, coexistence, and longitudinal change in excessive daytime sleepiness (EDS), insomnia, and probable REM sleep behavior disorder (pRBD) in early PD. Methods Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI). EDS, insomnia, and pRBD were defined using the Epworth Sleepiness Scale, MDS-UPDRS Part I sub-item 1.7, and RBD screening questionnaire. Results 218 PD subjects and 102 controls completed 5 years of follow-up. At baseline, 69 (31.7%) PD subjects reported one type of sleep disturbance, 25 (11.5%) reported two types of sleep disturbances, and three (1.4%) reported all three types of sleep disturbances. At 5 years, the number of PD subjects reporting one, two, and three types of sleep disturbances was 85 (39.0%), 51 (23.4%), and 16 (7.3%), respectively. Only 41(18.8%) patients were taking sleep medications. The largest increase in frequency was seen in insomnia (44.5%), followed by EDS (32.1%) and pRBD (31.2%). Insomnia was the most common sleep problem at any time over the 5-year follow-up. The frequency of sleep disturbances in HCs remained stable. Conclusions There is a progressive increase in the frequency of sleep disturbances in PD, with the number of subjects reporting multiple sleep disturbances increasing over time. Relatively a few patients reported multiple sleep disturbances, suggesting that they can have different pathogenesis. A large number of patients were not treated for their sleep disturbances.

We compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement].In the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival.Of 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05-6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60-5.76) and ILD (HR 1.84, 95% CI: 1.04-3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13-5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups.PAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

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.

To determine the rate of prophylactic embolization of extrahepatic vessels in patients undergoing yttrium-90 selective internal radiotherapy (90Y SIRT) for hepatocellular carcinoma (HCC) with the use of catheter-directed computed tomography hepatic angiography (CD-CTHA). This retrospective study included 186 HCC patients who received 90Y SIRT from May 2010 to June 2015 in a single institution. All procedures were performed in a hybrid angiography-CT suite equipped with digital subtraction angiography (DSA) and CD-CTHA capabilities. CD-CTHA was performed during pre-treatment hepatic angiography. 90Y SIRT was administered approximately 2 weeks later. Selective prophylactic embolization of extrahepatic vessels was performed if extrahepatic enhancement was seen on CD-CTHA or if an extrahepatic vessel opacified on DSA/CD-CTHA despite the final microcatheter position for 90Y microsphere delivery being beyond the origin of this vessel. Thirty-five patients (18.8%) required selective embolization of extrahepatic vessels. Technical success of 90Y SIRT was 99.5%. Two patients (1.1%) developed radiation-induced gastrointestinal ulceration, and one (0.54%) developed radiation-induced pneumonitis. Extrahepatic uptake of 90Y microspheres was seen in the gallbladder of one patient without significant complications. The use of CD-CTHA in 90Y SIRT of HCC was associated with a low rate of prophylactic embolization of extrahepatic vessels while maintaining a high technical success rate of treatment and low rate of complications. Level 4, case series.

ObjectivesDiazoxide (DZX) is the drug of choice for treating hyperinsulinaemic hypoglycaemia (HH), and it has potentially serious adverse effects. We studied the safety and efficacy of low-dose DZX in small-for-gestational-age (SGA) infants with HH.DesignAn observational cohort study from 1 September 2014 to 31 September 2020.SettingA tertiary Women’s and Children’s Hospital in Singapore.PatientsAll SGA infants with HH.InterventionDiazoxide, at 3–5 mg/kg/day.Main outcome measuresShort-term outcomes; adverse drug events and fasting studies to determine ‘safe to go home’ and ‘resolution’ of HH.ResultsAmong 71 836 live births, 11 493 (16%) were SGA. Fifty-six (0.5%) SGA infants with HH were identified, of which 27 (47%) with a mean gestational age of 36.4±2 weeks and birth weight of 1942±356 g required DZX treatment. Diazoxide was initiated at 3 mg/kg/day at a median age of 10 days. The mean effective dose was 4.6±2.2 mg/kg/day, with 24/27 (89%) receiving 3–5 mg/kg/day. Generalised hypertrichosis occurred in 2 (7.4%) and fluid retention in 1 (3.7%) infant. A fasting study was performed before home while on DZX in 26/27 (96%) cases. Diazoxide was discontinued at a median age of 63 days (9–198 days), and resolution of HH was confirmed in 26/27 (96%) infants on passing a fasting study.ConclusionOur study demonstrates that low-dose DZX effectively treats SGA infants with HH as measured by fasting studies. Although the safety profile was excellent, minimal adverse events were still observed with DZX, even at low doses.

Objectives: To evaluate the effect of a musculoskeletal ultrasound programme (MUSP) applying real-time ultrasonography with reinforcement of findings by a rheumatologist on improving disease-modifying anti-rheumatic drugs (DMARDs) adherence in rheumatoid arthritis (RA).Method: Eligible RA patients with low adherence score ( 0.05). All 62 patients completed the MUSP (mean time taken, 9.2 min), with the majority reporting moderately/very much improved understanding of their joint condition (71%) and the importance of regularly taking their RA medication(s) (79%). Most patients (90.3%) would recommend the MUSP to another RA patient.Conclusions: The MUSP improved RA patients' DMARDs adherence in the short term and was feasible and well accepted by patients. Future studies could evaluate whether repeated feedback using MUSP could help to sustain the improvement in DMARD adherence in RA patients, and whether this may be clinically impactful and cost-effective.

Background and purpose Although COVID‐19 predominantly affects the respiratory system, recent studies have reported the occurrence of neurological disorders such as stroke in relation to COVID‐19 infection. Encephalitis is an inflammatory condition of the brain that has been described as a severe neurological complication of COVID‐19. Despite a growing number of reported cases, encephalitis related to COVID‐19 infection has not been adequately characterised. To address this gap, this systematic review and meta‐analysis aims to describe the incidence, clinical course, and outcomes of patients who suffer from encephalitis as a complication of COVID‐19. Methods All studies published between 1 November 2019 and 24 October 2020 that reported on patients who developed encephalitis as a complication of COVID‐19 were included. Only cases with radiological and/or biochemical evidence of encephalitis were included. Results In this study, 610 studies were screened and 23 studies reporting findings from 129,008 patients, including 138 with encephalitis, were included. The average time from diagnosis of COVID‐19 to onset of encephalitis was 14.5 days (range = 10.8–18.2 days). The average incidence of encephalitis as a complication of COVID‐19 was 0.215% (95% confidence interval [CI] = 0.056%–0.441%). The average mortality rate of encephalitis in COVID‐19 patients was 13.4% (95% CI = 3.8%–25.9%). These patients also had deranged clinical parameters, including raised serum inflammatory markers and cerebrospinal fluid pleocytosis. Conclusions Although encephalitis is an uncommon complication of COVID‐19, when present, it results in significant morbidity and mortality. Severely ill COVID‐19 patients are at higher risk of suffering from encephalitis as a complication of the infection.

BackgroundPersons with mild stroke experience minimal functional difficulties; nonetheless, they are at elevated risk for post-stroke cognitive impairment (PSCI) and cognitive decline. AimsWe report outcomes from an observational cohort study of a structured, multidomain intervention for persons with mild strokes. MethodsThe Stroke Memory RehabiliTation (SMaRT) program comprises weekly two-hour group sessions for six weeks on cognitive strategies, lifestyle and relaxation. Participants were recruited from a tertiary hospital between June 2018 to September 2019. They had MRI-confirmed ischemic strokes with mild functional difficulties (modified Rankin Scale score ≤3). Participants underwent assessments and questionnaires at baseline, 1-week post-program, 3 months post-program, and 6 months post-program. Results Participants (N=108, mean age=63.54±9.22, 31.5% female) demonstrated significant improvement in cognition, mood, activities of daily living (ADL) and quality of life (QOL) (ps vs. 25.80±2.83, Beta=1.26, 95% CI(0.78,1.74)), pppppConclusionsThe SMaRT program is a cost-effective, scalable, structured program for PSCI. Findings suggest its potential effectiveness in reducing cognitive decline and improving other domains of well-being, with carry-over benefits after 6 months.

Introduction: It is yet to be understood how COVID-19 impacted utilisation of Emergency Department (ED) services in Singapore. This study aimed to describe the changes in attendance of a single ED and corresponding patient visit characteristics and outcomes before and during the COVID-19 period.Methods: In a single-centre retrospective cohort study, we used descriptive statistics to compare ED attendance, patient demographics and visit characteristics during the COVID-19 period (1 January – 28 June 2020) and its corresponding historical period in 2019 (2 January – 30 June 2019).Results: Mean ED attendance decreased from 342 visits/day in the pre-COVID-19 period, to 297 visits/day in the COVID-19 period. This was accompanied by reductions in P1 visits and presentations in nearly every ICD-10-CM diagnosis category except for respiratory-related diseases. We also noted a shift in ED patient case-mix from ‘Non-fever’ cases to ‘Fever’ cases, likely giving rise to two distinct trough-to-peak visit patterns during the pre-Circuit Breaker and Circuit Breaker period. Average ED admission rate during the Circuit Breaker period (48.3%) was higher as compared to pre-Circuit Breaker period (40.7%), however average daily admission remained stable.Conclusion: The COVID-19 pandemic caused a reduction in SGH ED attendances amongst patients with low-acuity conditions and those with highest priority for emergency care. This raises concern about treatment-seeking delays and possible impact on health outcomes. Our data provides insights that may be useful for ED crowd management planning in the post-COVID-19 era. There should be cautious use of ED admission rate as a metric in evaluating ED performance during an outbreak.

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; Results Dementia of the Alzheimer’s type (DAT) was the most common diagnosis (59.8%), followed by vascular dementia (14.9%) and frontotemporal dementia (11.1%). YOD patients accounted for 28.5% of all dementia patients. Patients with higher lifespan education had a steeper decline in global cognition (pp=0.0006). Older patients with a moderate-to-severe burden of CVD demonstrated a trend for a faster decline in global cognition compared to those with a mild burden. Conclusions There is a high frequency of YOD with DAT being most common in our Southeast Asian memory clinic cohort. YOD patients with higher lifespan education and LOD patients with moderate-to-severe CVD experience a steep decline in cognition.

Introduction COVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis. The consequences of this include renal dysfunction, hepatitis and stroke. In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19. Methods We conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19. Results 326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included. The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4–76.4 years). The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%). The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%). These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts. Conclusion Although stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality. In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.

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 p p = 0.039). Within the PIGD group, higher NfL associated significantly with worse global cognition and UPDRS motor scores at baseline, and was able to predict motor and cognitive decline at a mean follow-up duration of 1.9 years, controlled for age, sex and disease duration. Conclusions In this longitudinal study, we demonstrated for the first time the potential utility of plasma NfL as a diagnostic and prognostic biomarker in PIGD even at early stages of PD. These important novel findings will require further confirmation in larger, longitudinal PD cohorts.

Background Acute ischemic stroke is a time-sensitive emergency where accurate diagnosis is required promptly. Due to time pressures, stroke mimics, whom 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 aim to 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 whom 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), although it was not statistically significantly better. 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 (88.1–97.5%) and low negative predictive values (4.7–32.3%). 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 well to identify stroke mimics in the emergency setting. A novel decision tree may improve the identification of stroke mimics.

Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) face long-term disturbance in bowel function even after definitive surgery. This study evaluates the quality of life (QOL) of patients with ARM and HD, and compares them to healthy controls using self-report questionnaires.A prospective study was performed recruiting patients with ARM or HD from September 2013 to December 2014 who had primary surgery done in our institution at least 2 years prior to participation. Age-matched and gender-matched controls were enrolled from our patients with minor outpatient complaints. All participants completed the following PedsQL™ scales (maximum score 100): 4.0 Generic Core Scales, 3.0 General Well-Being (GWB) Scale and 2.0 Family Impact (FI) Module. All were also scored on bowel function (BFS), with a maximum score 20. Appropriate statistical analysis was performed, with significance level0.05.There were 193 participants: 87 controls, 62 ARM, 44 HD. When comparing Core, GWB and FI scores, there were no significant differences between groups although controls had best scores indicating best QOL and general wellbeing, with least impact of the child's health on the family. BFS was significantly different with controls having best and ARM worst scores. There were no significant differences in scores between parent and child indicating intradyad consistency. There was significant positive correlation between BFS and Core (p0.0001), and between BFS and GWB scores (p0.005); and significant negative correlation between BFS and FI scores (p0.0001).Bowel function impacts quality of life. Those with ARM and HD can achieve good quality of life comparable to controls, based on patient and caregiver self-reported outcomes.Prospective comparative study LEVEL OF EVIDENCE: Level II.

Background The prevalence of peanut allergy (PA) among children has increased significantly over the past decade. Even though the prevalence of PA in Singapore is considered low, peanut is the top trigger for food-induced anaphylaxis in Singaporean children. Objective To describe the demographic characteristics and clinical features of children with PA. Methods This is a 5-year retrospective review of children diagnosed with PA based on clinical history coupled with a positive skin prick test to peanut or positive oral food challenge results. Results There were 269 patients (53.9% males) with a clinical diagnosis of PA. The median age at first allergic presentation for the PA group was 24 months old, with interquartile range of 13-39 months. The most common form of peanut introduced was roasted peanut. The rate of peanut anaphylaxis was 7.1%. Concomitant tree nut sensitization was found in 32.3% of this cohort, predominantly to cashew nut. Majority of them have a personal history of atopy - 75.8% with eczema, 63.6% with allergic rhinitis, and 19.7% with asthma. Conclusion This is the first large review of peanut-allergic children in Singapore. Prospective population-based studies are needed to establish the true prevalence and risk factors associated with the development of this potentially life-threatening condition.

BACKGROUND Cow's milk protein allergy (CMA) is the second most common food allergy in Singapore. However, there is limited data on local paediatric CMA. OBJECTIVE We aimed to describe the demographics, clinical characteristics, natural history and diagnostic performance of skin prick test (SPT) and cow's milk-specific immunoglobulin E (CM-IgE) in Singaporean children diagnosed with IgE-mediated CMA. METHODS A retrospective review of medical records was conducted for children with an SPT performed to cow's milk between 2011 and 2016. RESULTS There were 355 patients included, 313 cow's milk allergic and 42 cow's milk tolerant. The median age of reaction was 6 months (IQR 4-8). The most common allergic presentation was cutaneous reactions, followed by gastrointestinal reactions. Six patients (1.9%) reported anaphylaxis at initial presentation and 16 children (5.1%) experienced anaphylaxis to cow's milk at least once in their lifetime. Most of the CMA patients (81.8%) acquired natural tolerance by 6 years old. SPT to cow's milk of ≥ 7 mm and CM-IgE of ≥ 13 kU/L showed good discriminative abilities in predicting a failed oral food challenge (OFC) outcome. CONCLUSION CMA is a food allergy which commonly presents during infancy, and parents need to be aware of the likelihood of severe allergic reactions, including anaphylaxis. Prognosis for CMA is generally favourable. Future prospective cohort studies are required to better understand the natural history and better define the diagnostic cut-off values for allergy testing in our population.

BACKGROUND While the association between alpha-synuclein gene promoter (Rep1) variability and risk of PD is well established, its association with cognition is unclear. OBJECTIVES To investigate the association between Rep1 and motor and cognitive outcomes in PD. METHODS Rep1 allele lengths were determined in 172 PD patients who were grouped into "long" and "short" carriers according to previous methods. Multivariable regression analysis was performed to investigate the effect of Rep1 length on cognitive and motor scores. RESULTS Long Rep1 allele carriers had significantly lower MMSE (P = 0.010) and higher UPDRS Part III (P = 0.026) and H & Y (P = 0.008) scores compared to short allele carriers (controlled for age, sex, and disease duration). Interaction analyses of Rep1 with apolipoprotein 4 revealed no significant effect on clinical outcomes. CONCLUSIONS PD patients carrying long Rep1 alleles are more impaired on cognitive and motor function independent of apolipoprotein 4 genotype. © 2019 International Parkinson and Movement Disorder Society.

OBJECTIVE Malignant internal carotid artery (ICA) infarction is an entirely different disease entity when compared with middle cerebral artery (MCA) infarction. Because of an increased area of infarction, it is assumed to have a poorer prognosis; however, this has never been adequately investigated. Decompressive craniectomy (DC) for malignant MCA infarction has been shown to improve mortality rates in several randomized controlled trials. Conversely, aggressive surgical decompression for ICA infarction has not been recommended. The authors sought to compare the functional outcomes and survival between patients with ICA infarctions and those with MCA infarctions after DC in the largest series to date to investigate this assumption. METHODS A multicenter retrospective review of 154 consecutive DCs for large territory cerebral infarctions performed from 2005 to 2020 were analyzed. Patients were divided into ICA and MCA groups depending on the territory of infarction. Variables, including age, sex, medical comorbidities, laterality of the infarction, preoperative neurological status, primary stroke treatment, and the time from stroke onset to DC, were recorded. Univariable and multivariable analyses were performed for the clinical exposures for functional outcomes (modified Rankin Scale [mRS] score) on discharge and at the 1- and 6-month follow-ups, and for mortality, both inpatient and at the 1-year follow-up. A favorable mRS score was defined as 0–2. RESULTS There were 67 patients (43.5%) and 87 patients (56.5%) in the ICA and MCA groups, respectively. Univariable analysis showed that the ICA group had a comparably favorable mRS (OR 0.15 [95% CI 0.18–1.21], p = 0.077). Inpatient mortality (OR 1.79 [95% CI 0.79–4.03], p = 0.16) and 1-year mortality (OR 2.07 [95% CI 0.98–4.37], p = 0.054) were comparable between the groups. After adjustment, a favorable mRS score at 6 months (OR 0.17 [95% CI 0.018–1.59], p = 0.12), inpatient mortality (OR 1.02 [95% CI 0.29–3.57], p = 0.97), and 1-year mortality (OR 0.94 [95% CI 0.41–2.69], p = 0.88) were similar in both groups. The overall survival, plotted using the Cox proportional hazard regression, did not show a significant difference between the ICA and MCA groups (HR 0.581). CONCLUSIONS Unlike previous smaller studies, this study found that patients with malignant ICA infarction had a functional outcome and survival that was similar to those with MCA infarction after DC. Therefore, DC can be offered for malignant ICA infarction for life-saving purposes with limited functional recovery.

Objective: To identify the fetal and neonatal imaging characteristics of meconium peritonitis (MP) and their clinical outcome. We also studied the role of prenatal ultrasound (US) in antenatal diagnosis and its use in predicting the need for surgical intervention postnatally. Material and Methods: We conducted a retrospective analysis of a cohort of 18 infants with MP from April 2004 to March 2014. Results: Prenatal US detected MP-related abnormalities in 15/18 (83.3%) fetuses. The median gestational age at initial diagnosis of MP was 24 weeks (range 19-31). Fetal ascites (93.3%) was the most common prenatal US finding. Of the 18 infants, 12 (66.7%) required surgical intervention. The overall survival rate was 94.4%. All infants with a prenatal US scan showing meconium pseudocyst or bowel dilatation required surgical intervention postnatally. Discussion: A combination of ascites, intraperitoneal calcification, and echogenic bowel on fetal US raises a high suspicion of MP. Surgical intervention is indicated in the presence of meconium pseudocyst on fetal or postnatal US scan. Antenatal US has high specificity (100%) but low sensitivity (22.2%) in detecting meconium pseudocyst. A favorable outcome can be expected with early antenatal diagnosis and timely surgical intervention in a tertiary hospital.

The above article was published with incorrect list of authors. We have added Seyed Ehasan Saffari and his affiliation as the addition of the new author to the author list was requested at revision stage.

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.

Background: Multidisciplinary pediatric weight management clinics have reported varying effectiveness in childhood obesity and they faced a common issue of high attrition rate. The effectiveness of pediatric weight management clinic and predictors of attrition has not been described in a multiracial Singapore population. Objectives: The aim of the study is to determine whether a dedicated multidisciplinary pediatric weight management program in a single center tertiary institution effectively reduces Body Mass Index (BMI) Z-Scores and cardiovascular risk factors in children with obesity aged 2-16 years old pre post intervention and to examine the factors that predict attrition from the program. Methods: This is a single center retrospective study, where medical records of patients enrolled in KK Women’s and Children’s Hospital paediatric weight mangement clinic over a 14 months period was reviewed. The program is a multicomponent family based clinic that utilizes medical management, dietary and physical activity counseling and intervention. Inclusion criteria for enrollment in the program was more than 2 years of age with BMI of more than 90th percentile. Attenders were defined as attending more than ≥ 2 clinic visit. Analyses were performed to identify factors associated with changes in BMI Z-Score and cardiovascular risk factors and attrition from the program. Results: A total of 121 patients were enrolled in the pediatric weight management program and 68% had obesity related comorbidities with dyslipidemia being the most common followed by hypertension. There were 51 attenders and presence of obesity related comorbidities predicted lower attrition rate (p=0.05). The attenders had a significant reduction in mean BMI Z-Score of 0.082 (95% CI,-0.13 to -0.033) (p=0.001) with significant improvements in high-density lipoprotein level and total cholesterol to high- density lipoprotein level (p

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis. Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined. Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF. Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF. Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM.

Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.