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Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension.
We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007–December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011–2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430–437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified.
In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03–1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00–1.67).
Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.
Several questions still exist in the literature on the relationship between cumulative exposure to work-related incidents and posttraumatic stress disorder (PTSD) in First Responders (FR).
To address three unanswered questions in the field.
(1) Are different cumulative exposure scoring algorithms similarly related to PTSD?
(2) Is PTSD associated only with incidents rated as severe and traumatic?
(3) Can we identify cut-off scores of cumulative exposure that maximize sensitivity and specificity to predict PTSD?
To better characterize the relationship between cumulative exposure and PTSD in FR.
The association between exposure and PTSD was examined with logistic and linear regression and with receiver operating characteristic analysis in 349 FR.
(1) The strength of the association between PTSD and total cumulative exposure indexes varied across different scoring algorithms.
(2) Compared to total cumulative exposure indexes and to sub-scores of exposure to non-traumatic and/or less severe incidents, sub-scores indexing exposure to severe traumatic events only were more strongly and significantly associated with PTSD.
(3) The use of two cut-off scores maximizes sensitivity and specificity to predict PTSD.
(1) The relationship between current PTSD and cumulative exposure is partially dependent on the approach used to quantify exposure.
(2) Focusing on the assessment of cumulative exposure to severe traumatic events is sufficient to predict PTSD, and might be more useful and effective in research and clinical decision-making.
(3) Sensitivity and specificity of exposure scores might help improve secondary prevention (early detection and effective intervention) of individuals at risk.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1. Explore the current molecular landscape of pediatric high grade gliomas
2. Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3. Discuss the current status of NTRK inhibitor clinical trials
There have been significant changes in the diagnostic criteria for diffuse gliomas in the 2016 WHO CNS tumor classification, with the incorporation of molecular criteria into a number of definitions. This has placed a greater emphasis on the availability of key immunohistochemical and molecular tests. In order to determine the effect that these changes have had on neuropathology practice and the access of different centres to these tests, we designed a survey that was sent to all members of the Canadian Association of Neuropathology member list in the fall of 2017. This survey asked a number of questions relating to the approach to glioma diagnosis, immunohistochemical/molecular test ordering patterns, in-house test availability, and need to send out for testing. In this presentation we will present preliminary results from this survey, with a focus on institutional testing capabilities. This provides a valuable resource that could ultimately need to a national database of immunohistochemical and molecular test availability for each neuropathology centre.
This presentation will enable the learner to:
1. Review the key molecular markers in the diagnosis of adult gliomas and methods of testing for them
2. Discuss the effect that the 2016 WHO CNS tumor update has had on clinical practice in Canada
Introduction: A significant gap exists between the number of people waiting for an organ and donors. There are currently 1,628 people awaiting organ donation in Ontario alone. In 2018 to date, 310 donors have donated 858 organs. The purpose of this study was to determine whether there were missed donors in the Emergency Department (ED) and by what percent those missed donors would increase organ donation overall. Methods: This was a health records and organ donation database review of all patients who died in the ED at a large academic tertiary care center with 2 campuses and 160,000 visits per year. Patients were included from November 1, 2014 – October 31, 2017. We collected data on demographics, cause of death, and suitability for organ donation. Data was cross-referenced between hospital records and the provincial organ procurement organization called Trillium Gift of Life Network (TGLN) to determine whether patients were appropriately referred for consideration of donation in a timely manner. Potential missed donors were manually screened for suitability according to TGLN criteria. We calculated simple descriptive statistics for demographic data and the primary outcome. The primary outcome was percentage of potential organ donors missed in the Emergency Department (ED). Results: There were 606 deaths in the ED from November 1, 2014 – October 31, 2017. Patients were an average of 71 years old, 353 (58%) were male, and 75 (12%) died of a traumatic cause. TGLN was not contacted in 12 (2%) of cases. During this period there were two donors from the ED and 92 from the ICU. There were ten missed potential donors. They were an average of 67 years, 7 (70%) were male, and 2 (20%) died of a traumatic cause. In all ten cases, patients had withdrawal of life sustaining measures for medical futility prior to TGLN being contacted for consideration of donation. There could have been an addition seven liver, six pancreatic islet, four small bowel, and seven kidney donors. The ten missed ED donors could have increased total donors by 11%. Conclusion: The ED is a significant source of missed organ donors. In all cases of missed organ donation, patients had withdrawal of life sustaining measures prior to TGLN being called. In the future, it is essential that all patients have an organ procurement organization such as TGLN called prior to withdrawal of life sustaining measures to ensure that no opportunity for consideration of organ donation is missed.
Introduction: Low acuity patients have been controversially tagged as a source of emergency department (ED) misuse. Authorities for many Canadian health regions have set up policies so these patients preferably present to walk-in clinics (WIC). We compared the cost and quality of the care given to low acuity patients in an academic ED and a WIC of Québec City during fiscal year 2015-16. Methods: We conducted an ambidirectional (prospective and retrospective) cohort study using a time-driven activity-based costing method. This method uses duration of care processes (e.g., triage) to allocate to patient care all direct costs (e.g., personnel, consumables), overheads (e.g., building maintenance) and physician charges. We included consecutive adult patients, ambulatory at all time and discharged from the ED or WIC with a diagnosis of upper respiratory tract infection (URTI), urinary tract infection (UTI) or low back pain. Mean cost [95%CI] per patient per condition was compared between settings after risk-adjustment for age, sex, vital signs, number of regular medications and co-morbidities using generalized log-gamma regression models. Proportions [95%CI] of antibiotic prescription and chest X-Ray use in URTI, compliance with provincial guidelines on use of antibiotics in UTI, and column X-Ray use in low back pain were compared between settings using a Pearson Chi-Square test. Results: A total of 409 patients were included. ED and WIC groups were similar in terms of age, sex and vital signs on presentation, but ED patients had a greater burden of comorbidities. Adjusted mean cost (2016 CAN$) of care was significantly higher in the ED than in the WIC (p < 0.0001) for URTI (78.42[64.85-94.82] vs. 59.43[50.43-70.06]), UTI (78.88[69.53-89.48] vs. 53.29[43.68-65.03]), and low back pain (87.97[68.30-113.32] vs. 61.71[47.90-79.51]). For URTI, antibiotics were more frequently prescribed in the WIC (44.1%[34.3-54.3] vs. 5.8%[1.2-16.0]; p < 0.0001) and chest X-Rays, more frequently used in the ED (26.9%[15.6-41.0] vs. 13.7%[7.7-22.0]; p = 0.05). No significant differences were observed in the compliance with guidelines on use of antibiotics in UTI and in the use of column X-Ray in low back pain. Conclusion: Total cost of care for low acuity patients is lower in walk-in clinics than in EDs. However, our results suggest that quality-of-care issues should be considered in determining the best alternate setting for treating ambulatory emergency patients.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
The classification system for gliomas has undergone significant revisions in the last several years, with the incorporation of molecular criteria and removal of mixed histologic diagnoses. Large-scale molecular studies have elucidated the biological characteristics of low grade gliomas, and enabled grouping based on IDH mutational and 1p19q codeletion status that outperforms histology in predicting patient outcomes. Mutations in ATRX and TP53 are largely mutually exclusive of 1p19q- codeletion in the context of mutant IDH, and are useful in screening patients for further molecular studies.
At our institution, new testing methods for 1p19q codeletion and ATRX were implemented in 2014, and in this presentation we review all cases submitted for 1p19q testing since this time. In comparing histologic to molecular diagnoses, the majority of histologic oligodendrogliomas indeed have 1p19q codeletion, while oligoastrocytomas and GBMOs largely are re-classified as astrocytomas and glioblastomas, respectively. We have also found that loss of ATRX nuclear expression associated with ATRX mutation is highly indicative of 1p19q retention, however the immunohistochemical test can be challenging to interpret and there have been a small number of discordant results.
Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.
There has recently been an increased interest in mental health indicators for the monitoring of population wellbeing, which is among the targets of Sustainable Development Goals adopted by the United Nations. Levels of subjective wellbeing and suicide rates have been proposed as indicators of population mental health, but prior research is limited.
Data on individual happiness and life satisfaction were sourced from a population-based survey in Hong Kong (2011). Suicide data were extracted from Coroner's Court files (2005–2013). Area characteristic variables included local poverty rate and four factors derived from a factor analysis of 21 variables extracted from the 2011 census. The associations between mean happiness and life satisfaction scores and suicide rates were assessed using Pearson correlation coefficient at two area levels: 18 districts and 30 quantiles of large street blocks (LSBs; n = 1620). LSB is a small area unit with a higher level of within-unit homogeneity compared with districts. Partial correlations were used to control for area characteristics.
Happiness and life satisfaction demonstrated weak inverse associations with suicide rate at the district level (r = −0.32 and −0.36, respectively) but very strong associations at the LSB quantile level (r = −0.83 and −0.84, respectively). There were generally very weak or weak negative correlations across sex/age groups at the district level but generally moderate to strong correlations at the LSB quantile level. The associations were markedly attenuated or became null after controlling for area characteristics.
Subjective wellbeing is strongly associated with suicide at a small area level; socioeconomic factors can largely explain this association. Socioeconomic factors could play an important role in determining the wellbeing of the population, and this could inform policies aimed at enhancing population wellbeing.
Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.
In recent years, various pro-natalist policies have been adopted in Singapore and other high-income Asian countries with low fertility, aiming at raising fertility rates. Previous studies were mainly focused on the impact or outcome of the policies. This paper, however, aims to identify the most influential groups in determining Singapore's total fertility rate (TFR) and evaluate the targeting of pro-natalist measures adopted by the government. We first reveal the changing age-parity-and-marital-status composition of women at childbearing age, and further conduct an elasticity analysis to assess the roles of different subgroups of women in changing the TFR. Our results show that compared to other groups, the 20–29-year-old single women and the married childless women aged 30–34 (‘married’ throughout this paper includes women who are or have been married) are more influential in determining the TFR and should be the potential pro-natalist target groups. However, Singapore's pro-natalist policies are more in favour of third and higher-order births. Such mismatch indicates that, if more efforts are devoted to facilitating marriage and first births in these potential groups, the TFR may be increased effectively. In order to achieve a long-term and significant fertility reversal, it calls for a long-term and integrated policy package.
Somatic mutations in the Capicua (CIC) gene were first identified in Type I low-grade gliomas (LGGs), which are characterized by 1p/19q co-deletions and IDH mutations. They are found at frequencies of ~50-70% in this glioma subtype, and have since been identified in ~40% of stomach adenocarcinomas (STADs) of the microsatellite instability (MSI) subtype; however, the role of these somatic mutations in malignancy has yet to be established. In Drosophila, CIC functions as a transcriptional repressor whose activity is inhibited upon activation of the mitogen-activated protein kinase (MAPK) signalling pathway. Though mammalian CIC appears to retain these functions, only three of its target genes have been established in human cells: ETV1, ETV4, and ETV5 (ETV1/4/5). To further probe CIC’s transcriptional network, we developed CIC knockout cell lines and performed transcriptomic and proteiomic analyses in these and in control cell lines expressing wild type CIC, identifying a total of 582 differentially expressed genes. We also used RNA-seq data from The Cancer Genome Atlas (TCGA) for Type I LGGs and STADs to perform additional differential expression analyses between CIC-deficient and CIC-expressing samples. Though gene-level overlap was limited between the three contexts, we found that CIC appears to regulate the expression of genes involved in cell-cell adhesion, metabolism, and developmental processes in all three contexts. These results shed light on the pathological role of CIC mutations and may help explain why these have been associated with poorer outcome within Type I LGGs.
Background: Ischemic stroke secondary to NBTE is a rare complication of systemic malignancies. Although previously reported in gynecological cancers, this occurrence is infrequent. Furthermore, stroke pre-dating the gynecological malignancy diagnosis has rarely been reported. Methods: Case presentations and literature review. Results: Case1: A 48-year-old woman presented with acute dysarthria and left facial weakness caused by a right middle cerebral artery (MCA) infarct. Mitral valve vegetations were found on a transthoracic echocardiogram (TTE). A malignancy screen uncovered a pelvic endometrial adenocarcinoma. Case 2: A 49-year-old woman developed acute right hand weakness. A CT head scan showed a left pre-central gyrus infarct. Her TEE revealed aortic valve vegetations. An ovarian neoplasm was then discovered. Case 3: A 36-year-old woman with a known diagnosis of cervical squamous cell carcinoma developed acute left-sided weakness secondary to a right MCA stroke. Aortic valve vegetations were seen on TTE. Conclusions: We have reported three cases of NBTE where the underlying malignancy was gynecological. In the first two cases, the malignancy was discovered while investigating for the stroke mechanism, while the third had a known underlying malignancy. This series highlights the need to consider gynecological malignancies as an underlying cause of stroke in young women; and that the ischemic event can occur prior to the malignancy diagnosis.
This study aimed to monitor the microbiological effect of cleaning near-patient sites over a 48-hour period with a novel disinfectant, electrolyzed water.
One ward dedicated to acute care of the elderly population in a district general hospital in Scotland.
Lockers, left and right cotsides, and overbed tables in 30 bed spaces were screened for aerobic colony count (ACC), methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA) before cleaning with electrolyzed water. Sites were rescreened at varying intervals from 1 to 48 hours after cleaning. Microbial growth was quantified as colony-forming units (CFUs) per square centimeter and presence or absence of MSSA and MRSA at each site. The study was repeated 3 times at monthly intervals.
There was an early and significant reduction in average ACC (360 sampled sites) from a before-cleaning level of 4.3 to 1.65 CFU/cm2 at 1 hour after disinfectant cleaning (P <.0001). Average counts then increased to 3.53 CFU/cm2 at 24 hours and 3.68 CFU/cm2 at 48 hours. Total MSSA/MRSA (34 isolates) decreased by 71% at 4 hours after cleaning but then increased to 155% (53 isolates) of precleaning levels at 24 hours.
Cleaning with electrolyzed water reduced ACC and staphylococci on surfaces beside patients. ACC remained below precleaning levels at 48 hours, but MSSA/MRSA counts exceeded original levels at 24 hours after cleaning. Although disinfectant cleaning quickly reduces bioburden, additional investigation is required to clarify the reasons for rebound contamination of pathogens at near-patient sites.
Infect Control Hosp Epidemiol 2014;35(12):1505–1510
Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design.
Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed.
Results suggested that EI patients had reduced suicide rate (χ2(1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR −0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery.
The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.