Impact of Comorbidities and Drug Interactions in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Androgen Receptor Pathway Inhibitors.

PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described. METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley's databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed. RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P = .04) and poorer overall survival (28 v 45 months, P = .04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences. CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes.

Remdesivir therapy for severe pediatric COVID-19 in Singapore: A single-center retrospective observational cohort study.

Background and Aims: There is a paucity of information on remdesivir (RDV) use in severe pediatric coronavirus disease 2019 (COVID-19). We aimed to explore the effectiveness of RDV as the cumulative proportion of pediatric COVID-19 patients deescalated from Day 5 of high dependency or intensive care unit (HD/ICU). Methods: All children ≤18 years admitted to Singapore's largest pediatric hospital from January 1, 2020 to March 18, 2022 were reviewed retrospectively. Patients were included if they were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction, required oxygen, and HD/ICU care. The characteristics and outcomes of those who received RDV or not (no-RDV) were compared. Results: We reviewed 15 children with a median age of 2.5 years (interquartile range [IQR]: 0.8-11.0), of which 7 (46.7%) received RDV. There was no difference in cumulative proportion of children deescalated from Day 5 of HD/ICU care in the RDV versus the no-RDV group (5/7, 70% vs. 7/8, 87.5%, p = 0.57). The RDV versus no-RDV group had higher disease severity, that is, WHO Ordinal Scale scores (median 6, IQR: 5-7 vs. 5, IQR: 4-5, p = 0.03), higher procalcitonin levels (ug/L) (median 4.31, IQR: 0.8-24.2 vs. 0.12, IQR: 0.09-0.26, p = 0.02), and longer HD/ICU care days (median 5, IQR: 4-9, vs. 1, IQR: 1-4, p = 0.01). There was no significant difference in hospitalization days. There were no adverse events directly attributable to RDV. None died from COVID-19 infection. Conclusion: Our observational analysis was unable to detect any clear benefit of RDV in terms of reducing duration in HD/ICU. RDV was well-tolerated in children with severe COVID-19.

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease.

The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point-of-care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high-resolution mass spectrometry-based quantitative proteomics technology. We identified 19 upregulated (fold change = 1.5-5.8) and 51 downregulated proteins (fold change = 0.1-0.6) in the saliva samples of HFMD patients in comparison to that of healthy volunteers. Four upregulated protein candidates were selected for dot blot-based validation assay, based on novelty as biomarkers and exclusions in oral diseases and cancers. Salivary legumain was validated in the Singapore (n = 43 healthy, 28 HFMD cases) and Taiwan (n = 60 healthy, 47 HFMD cases) cohorts with an area under the receiver operating characteristic curve of 0.7583 and 0.8028, respectively. This study demonstrates the feasibility of a broad-spectrum HFMD POC diagnostic test based on legumain, a virus-specific host systemic signature, in saliva.

Paediatric actinomycosis: A 16-year, single-institution retrospective review of cases.

AIM: Actinomycosis is a rare subacute to chronic granulomatous infection which can mimic other infectious or malignant diseases. This study examined the epidemiology and treatment outcome of actinomycosis in children. METHODS: A retrospective study on children admitted for actinomycosis in a tertiary paediatric hospital in Singapore, from January 2004 to December 2020. Clinical profile, therapeutic interventions and outcomes were examined. RESULTS: A total of 10 patients were identified; 7 were female. The median age at first presentation was 9.8 years (range 4.7-15.7). The most common presenting symptom was fever (n = 6, 60%), followed by facial or neck swelling (n = 3, 30%) and ear pain (n = 3, 30%). Actinomycosis occurred predominantly in the orocervicofacial region (n = 6, 60%). Four patients (40%) had preceding dental infections in the form of dental caries or gingivitis. One patient had poorly controlled insulin-dependent diabetes mellitus. Actinomycosis was confirmed via culture in four patients, histopathology in four patients and both methods in two patients. All except one patient (n = 9, 90%) underwent surgical procedures. All patients received ampicillin or amoxicillin/clavulanate or other beta-lactams, for a median duration of 6.5 months (range 1.5-14). Complications included osteomyelitis (n = 4, 40%), mastoiditis (n = 2, 20%), brain abscess (n = 1, 10%) and recurrent neck abscess (n = 1, 10%). There was no mortality and all patients achieved complete resolution. CONCLUSIONS: Paediatric actinomycosis was rare in our 16-year review, but had a high complication rate. It can occur in immunocompetent patients, and dental infection was the predominant risk factor identified. Prognosis was excellent after surgical intervention and appropriate antimicrobial therapy.

Co-prevalence and incidence of myocardial infarction and/or stroke in patients with depression and/or anxiety: A systematic review and meta-analysis.

OBJECTIVE: Co-prevalence and incidence of depression and/or anxiety with stroke and myocardial infarction are currently unclear. This paper explores the relationships, as these are important comorbidities affecting patient outcomes. METHODS: A systematic search across five databases (PubMed, Scopus, PsycINFO, Embase, Cochrane) was conducted for observational studies reporting co-prevalence of depression or anxiety with stroke or myocardial infarction. We used random-effects models in all meta-analyses and evaluated heterogeneity using I2. RESULTS: This analysis included 48 studies with a total of 57,342 patients. In patients with depression, the pooled prevalence of stroke was 5.9% (95% CI = 5.53-6.37). In patients with myocardial infarction, the pooled prevalence of anxiety and depression was 9.1% (95% CI = 7.07-11.40, I2 = 85.6%) and 25.9% (95% CI = 18.46-34.12, I2 = 99.1%), respectively, and the pooled cumulative incidence of depression at one year was 20.5% (95% CI = 18.36-22.79). The pooled prevalence of anxiety and depression in patients with stroke was 13.5% (95% CI = 7.67-22.66, I2 = 96.9%) and 23.0% (95% CI = 17.93-28.99, I2 = 96.7%), respectively. The pooled cumulative incidences of depression at two weeks, three months, six months, and one year, were 29.1% (95% CI = 26.60-31.81), 17.0% (95% CI = 10.74-25.92, I2 = 98.0%), 7.4% (95% CI = 6.52-8.49), and 9.1% (95% CI = 3.71-20.79, I2 = 99.8%), respectively. CONCLUSIONS: This meta-analysis outlines the co-morbid burden between depression/anxiety and stroke/myocardial infarction. Future research should be done to evaluate the effectiveness of screening anxiety/depression in myocardial infarction/stroke.

SARS-CoV-2 antigen rapid tests and universal screening for COVID-19 Omicron variant among hospitalized children.

BACKGROUND: Clinical utility of universal antigen rapid test (ART) in the pediatric setting is unknown. We aimed to assess the performance and utility of universal ART in hospitalized children (≥5-year-old) to prevent nosocomial COVID-19 transmission. METHODS: Cross-sectional study involving all hospitalized pediatric patients aged ≥5-year-old from 2 periods during Omicron wave. Clinical data, ART and polymerase chain reaction test results were collected. RESULTS: A total of 444 patients were included from the 2 study periods, and 416 patients (93.7%) had concordant results between ART and polymerase chain reaction. The overall sensitivity and specificity of ART were 83.3% (95% CI: 75.2-89.3) and 97.5% (95% CI: 95.0-98.8), respectively. Negative predictive values of ART between the Omicron emergence and Omicron peak periods for a probable case group were 71.4% and 66.7%, respectively, and for a suspect case group 91.4% and 75.0%, respectively. Negative predictive values for an unlikely case group was >95% in both periods. Positive predictive value of ART was >85% for probable and suspect case groups in both periods. Seventy-five percent of patients (n = 15) who were incorrectly classified as SARS-CoV-2 negative by ART had potentially viable virus. No large nosocomial transmission clusters were detected. CONCLUSIONS: Universal ART screening may limit nosocomial outbreaks in hospitalized children. The performance can be optimized by considering clinical symptoms, exposure and periods within COVID waves.

Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of ß-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of brain function. TgSwDI is a well-studied transgenic mouse model of AD, but no longitudinal studies have been performed to characterize cognitive deficits or ß-amyloid plaque accumulation for use as a baseline reference in future research. Thus, we use behavioral tests (T-Maze, Novel Object Recognition (NOR), Novel Object Location (NOL)) to study long-term and working memory, and immunostaining to study ß-amyloid plaque deposits, as well as brain size, in hippocampal, cerebellum, and cortical slices in TgSwDI and wild-type (WT) mice at 3, 5, 8, and 12 months old. The behavioral results show that TgSwDI mice exhibit deficits in their long-term spatial memory starting at 8 months old and in long-term recognition memory at all ages, but no deficits in their working memory. Immunohistochemistry showed an exponential increase in ß-amyloid plaque in the hippocampus and cortex of TgSwDI mice over time, whereas there was no significant accumulation of plaque in WT mice at any age. Staining showed a smaller hippocampus and cerebellum starting at 8 months old for the TgSwDI compared to WT mice. Our data show how TgSwDI mice differ from WT mice in their baseline levels of cognitive function and ß-amyloid plaque load throughout their lives.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

Effectiveness of maternal pertussis vaccination in Singapore: A test-negative case-control study.

Pertussis vaccination (Tdap -Tetanus-diphtheria-acellular pertussis) for pregnant women has been recommended since November 2017 in Singapore. In this prospective test-negative case-control study from 2018 to 2019, we aimed to evaluate vaccine effectiveness (VE) against pertussis infection and pertussis-related intensive care unit (ICU) admission according to Tdap (Tetanus-diphtheria-acellular pertussis) during pregnancy and/or infant pertussis vaccination. A total of 58 children (26 cases, 32 controls) were recruited with 4 ICU admissions. The median age was 3 months (interquartile range [IQR] 1.50-4.56 months). Overall, 25.9 % of mothers had received antenatal Tdap vaccination and 43.1 % of infants received pertussis vaccination, majority only 1 dose. Tdap in pregnancy alone without infant vaccine or with 0-1 infant dose had a VE of 97.62 % (95 % confidence interval [CI] 53.25-99.88 %), 98.17 % (95 %CI 66.61-99.9 %) respectively, against pertussis infection and 71.9 % (95 %CI 0.0-98.64), 75.86 % (95 % CI 0.0-98.78) respectively, against ICU admissions. Conclusion: Maternal Tdap vaccination was highly protective against infant pertussis and should be routinely recommended for all pregnant women.

Analysis of Neutralizing Antibody Levels in Children and Adolescents Up to 16 Months After SARS-CoV-2 Infection.

This cohort study assesses the presence of neutralizing antibodies in the serum samples of children in different age groups during and after SARS-CoV-2 infection.

The use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

OBJECTIVE: The primary objective is to evaluate the use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease. BACKGROUND: There has been a rising number of randomized controlled trials conducted in patients with coronary artery disease on the use of colchicine in reducing cardiovascular complications. Recent publications suggest colchicine reduces the risk of stroke and other cardiovascular events. METHODS: We performed a systematic review of known trials in the current literature to characterize the clinical characteristics and outcomes of colchicine treatment in patients with coronary artery disease. A literature search was performed in PubMed, Embase and SCOPUS using a suitable keyword search strategy from inception to 4 June 2021. All studies evaluating cardiovascular outcomes of colchicine treatment in patients with coronary artery disease were included. RESULTS: The systemic review included 5 randomized controlled trials assessing a total of 11,790 patients. Majority of studies used a colchicine dosing regimen of 0.5 mg once daily, with the median follow-up duration ranging from 6 to 36 months. Meta-analytic estimates for stroke incidence highlighted a statistically significant benefit for patients that were administered colchicine compared to placebo (OR 0.47, 95% CI 0.27-0.81, p = 0.006), and a non-significant benefit for myocardial infarction. There was no significant association between colchicine treatment and the adverse effects of gastrointestinal symptoms and myopathy/myalgia. CONCLUSIONS: The use of colchicine reduces the risk of stroke in patients with a history of coronary artery disease, without a significant increase in gastrointestinal and myopathy/myalgia adverse effects.

Pediatric COVID-19 Risk Factors in Southeast Asia-Singapore and Malaysia: A Test-Negative Case-Control Study.

There is a scarcity of population-level data of pediatric COVID-19 infection from Southeast Asia. This study aims to describe and compare epidemiological, clinical, laboratory and outcome data among pediatric COVID-19 cases versus controls in two neighboring countries, Singapore and Malaysia. We used a test-negative case-control study design recruiting all suspected COVID-19 cases (defined by either clinical or epidemiological criteria) from January 2020 to March 2021 admitted to two main pediatric centers in Singapore and Malaysia. Data were collected using a standardized registry (Pediatric Acute and Critical Care COVID-19 Registry of Asia). The primary outcome was laboratory-confirmed COVID-19. Univariate and multivariable logistic regression analysis was used to determine factors associated with COVID-19. This study included 923 children with median age of 4 (interquartile range 2-9) years. Of these, 35.3% were COVID-19 cases. Children with COVID-19 were more likely to be asymptomatic compared with controls (49.4 versus 18.6%; P < 0.0001). They were also less likely to develop respiratory complications, such as bronchitis or pneumonia, or organ dysfunction. Four (1.2%) of our COVID-19 patients required respiratory support compared with 14.2% of controls needing respiratory support. COVID-19 cases tended to have lower neutrophil count but higher hemoglobin compared with controls. There were no reported deaths of COVID-19 infection; in contrast, 0.7% of the control group died. In the multivariable analysis, older age, travel history, and close contact with an infected household member were associated with COVID-19 infection. This study shows that the majority of pediatric COVID-19 cases were of lesser severity compared with other community acquired respiratory infections.

Re-analysis of genomic data: An overview of the mechanisms and complexities of clinical adoption.

Re-analyzing genomic information from a patient suspected of having an underlying genetic condition can improve the diagnostic yield of sequencing tests, potentially providing significant benefits to the patient and to the health care system. Although a significant number of studies have shown the clinical potential of re-analysis, less work has been performed to characterize the mechanisms responsible for driving the increases in diagnostic yield. Complexities surrounding re-analysis have also emerged. The terminology itself represents a challenge because "re-analysis" can refer to a range of different concepts. Other challenges include the increased workload that re-analysis demands of curators, adequate reimbursement pathways for clinical and diagnostic services, and the development of systems to handle large volumes of data. Re-analysis also raises ethical implications for patients and families, most notably when re-classification of a variant alters diagnosis, treatment, and prognosis. This review highlights the possibilities and complexities associated with the re-analysis of existing clinical genomic data. We propose a terminology that builds on the foundation presented in a recent statement from the American College of Medical Genetics and Genomics and describes each re-analysis process. We identify mechanisms for increasing diagnostic yield and provide perspectives on the range of challenges that must be addressed by health care systems and individual patients.

Clinical profile of children with parechovirus meningitis in Singapore.

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1 year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127 days, with the majority (96%) being ≤ 90 days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90 days old, children with HPeV meningitis ≤ 90 days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90 days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90 days old (OR 6.3, 95% CI 2.7-14.2).

Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria's Undiagnosed Diseases Program.

BACKGROUND: Clinical exome sequencing typically achieves diagnostic yields of 30%-57.5% in individuals with monogenic rare diseases. Undiagnosed diseases programmes implement strategies to improve diagnostic outcomes for these individuals. AIM: We share the lessons learnt from the first 3 years of the Undiagnosed Diseases Program-Victoria, an Australian programme embedded within a clinical genetics service in the state of Victoria with a focus on paediatric rare diseases. METHODS: We enrolled families who remained without a diagnosis after clinical genomic (panel, exome or genome) sequencing between 2016 and 2018. We used family-based exome sequencing (family ES), family-based genome sequencing (family GS), RNA sequencing (RNA-seq) and high-resolution chromosomal microarray (CMA) with research-based analysis. RESULTS: In 150 families, we achieved a diagnosis or strong candidate in 64 (42.7%) (37 in known genes with a consistent phenotype, 3 in known genes with a novel phenotype and 24 in novel disease genes). Fifty-four diagnoses or strong candidates were made by family ES, six by family GS with RNA-seq, two by high-resolution CMA and two by data reanalysis. CONCLUSION: We share our lessons learnt from the programme. Flexible implementation of multiple strategies allowed for scalability and response to the availability of new technologies. Broad implementation of family ES with research-based analysis showed promising yields post a negative clinical singleton ES. RNA-seq offered multiple benefits in family ES-negative populations. International data sharing strategies were critical in facilitating collaborations to establish novel disease-gene associations. Finally, the integrated approach of a multiskilled, multidisciplinary team was fundamental to having diverse perspectives and strategic decision-making.

Recurrent de novo missense variants in GNB2 can cause syndromic intellectual disability.

PURPOSE: Binding proteins (G-proteins) mediate signalling pathways involved in diverse cellular functions and comprise Gα and Gßγ units. Human diseases have been reported for all five Gß proteins. A de novo missense variant in GNB2 was recently reported in one individual with developmental delay/intellectual disability (DD/ID) and dysmorphism. We aim to confirm GNB2 as a neurodevelopmental disease gene, and elucidate the GNB2-associated neurodevelopmental phenotype in a patient cohort. METHODS: We discovered a GNB2 variant in the index case via exome sequencing and sought individuals with GNB2 variants via international data-sharing initiatives. In silico modelling of the variants was assessed, along with multiple lines of evidence in keeping with American College of Medical Genetics and Genomics guidelines for interpretation of sequence variants. RESULTS: We identified 12 unrelated individuals with five de novo missense variants in GNB2, four of which are recurrent: p.(Ala73Thr), p.(Gly77Arg), p.(Lys89Glu) and p.(Lys89Thr). All individuals have DD/ID with variable dysmorphism and extraneurologic features. The variants are located at the universally conserved shared interface with the Gα subunit, which modelling suggests weaken this interaction. CONCLUSION: Missense variants in GNB2 cause a congenital neurodevelopmental disorder with variable syndromic features, broadening the spectrum of multisystem phenotypes associated with variants in genes encoding G-proteins.

Evaluating the safety and efficacy of intravenous thrombolysis for acute ischemic stroke patients with a history of intracerebral hemorrhage: a systematic review and meta-analysis.

Previous intracerebral hemorrhage (ICH) is labelled as a contraindication for the use of intravenous tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) based on expert opinion. However, there is a paucity of data available regarding the benefits and risks of IV-tPA in this population. Recent small retrospective cohort studies reporting its off-label use suggest it may be beneficial. This study aims to investigate the safety and efficacy of IV-tPA in AIS patients with previous ICH. We performed a systematic review and meta-analysis of studies reporting on IV-tPA use in AIS patients with and without previous ICH. We searched Embase, PubMed and Cochrane Library from inception to 20 April 2021. Outcomes measured included symptomatic ICH (sICH), 3-month modified Rankin Scale (mRS) score, and 3-month mortality. We included seven retrospective cohort studies comprising 5760 AIS patients who had received IV-tPA, of which 134 had previous ICH. There was no significant difference in the odds of sICH (OR 1.57, 95% CI 0.78-3.15, p = 0.21) and 3-month mRS (mRS 0-1: OR 0.78, 95% CI 0.37-1.65, p = 0.52; mRS 0-2: OR 1.07, 95% CI 0.36-3.15, p = 0.90) between patients with and without previous ICH. There was a trend towards higher 3-month mortality in patients with previous ICH (OR 1.69, 95% CI 0.98-2.91, p = 0.06), although this did not reach statistical significance. The use of IV-tPA in AIS patients with previous ICH was not associated with an increased risk of sICH or disability at 3 months. Further larger studies are needed to establish the safety and efficacy of IV-tPA use in this population.