Publications by authors named "Eric Chen"

621 Publications

Investigation of motor self-monitoring deficits in schizophrenia with passivity experiences using a novel modified joint position matching paradigm.

Eur Arch Psychiatry Clin Neurosci 2021 Apr 10. Epub 2021 Apr 10.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 222 New Clinical Building, 102 Pokfulam Road, Hong Kong SAR, China.

Numerous studies have identified deficits in the self-monitoring system that are associated with schizophrenia. However, the tasks used in the few previous studies generally involved complex cognitive processes and rarely compared between patients with and without passivity experiences (PE). Here, we examined the deficits in internal motor predictive representation in patients with and without PE, and in healthy controls using a novel paradigm which involved minimal cognitive processes. All participants completed a modified joint position matching (mJPM) task, in which they were required to replicate a voluntary, a passive verbally-cued, and a passive tactile-cued movement under blinded conditions. The absolute difference between the target spot and replicated spot was measured and compared. We hypothesised that if there was a failure in the internal motor predictive representation, patients with PEs would replicate less accurately in the voluntary condition, relative to passive conditions while the healthy controls would be more accurate, and, therefore, significant interactions between groups and conditions would be revealed. Both healthy controls and patients without PEs replicated more accurately in the voluntary condition compared with the passive conditions. The patients with PEs were less accurate in the voluntary condition compared with the passive tactile condition. A significant interaction was observed between patients with vs. without PEs × voluntary vs. passive tactile conditions. The findings suggested the relationship between deficits in motor self-monitoring in the prediction process and PEs, thus showing the need to highlight the link between motor performance and PEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-021-01261-zDOI Listing
April 2021

Induced ideas of reference during social unrest and pandemic in Hong Kong.

Schizophr Res 2021 Feb 19;229:46-52. Epub 2021 Feb 19.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong; State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong. Electronic address:

Ideas of reference (IOR) are often implicated in predicting psychosis onset. They have been conceptualized to present on a continuum, from oversensitive psychological reactions to delusional thoughts. It is however unknown to what extent IOR may be triggered by collective environmental stress. We obtained timely data from 9873 individuals to assess IOR in relation to trauma exposure in the 2019-2020 social unrest in Hong Kong. Two levels of IOR are distinguished: attenuated IOR (IOR-A), being the experience of feeling particularly referred to within a group; and exclusive IOR (IOR-E), the experience of feeling exclusively referred to while others are not. Logistic regressions showed that event-based rumination was a shared predictor for IOR-A (OR = 1.07, CI = 1.03-1.10) and IOR-E (OR = 1.09, CI = 1.02-1.17). For IOR-A, three categories of social unrest-related traumatic events (TEs) were significant predictors, including being attacked or having experienced sexual violence (OR = 4.14, CI = 1.93-8.85), being arrested (OR = 4.48, CI = 1.99-10.10), and being verbally abused (OR = 2.66, CI = 1.28-5.53). Being arrested was significant for IOR-E (OR = 3.87, CI = 1.03-14.52), though not when rumination was included. Education level also significantly predicted IOR-E (OR = 0.72, CI = 0.52-0.99). Further analysis revealed that rumination significantly mediated between TEs and IOR severity (β = 0.26, SE = 0.01, CI = 0.24-0.28). The findings are consistent with the hypothesis that IOR-A and IOR-E occur as levels on a continuum, but each has some distinctive correlates. Extrinsic events may play a more prominent role in IOR-A, while intrinsic factors, such as cognitive capacity, may play a more prominent role in IOR-E. The involvement of rumination across the IOR spectrum suggests an opportunity for intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.01.027DOI Listing
February 2021

Relationship between subjective quality of life and perceptions of recovery orientation of treatment service in patients with schizophrenia and major depressive disorder.

Asian J Psychiatr 2021 Mar 5;57:102578. Epub 2021 Feb 5.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong Special Administrative Region.

Objective: This study aimed to investigate the relationship between subjective quality of life (QOL) and the specific domains of perceptions of recovery orientation of treatment services in patients with schizophrenia and major depressive disorder (MDD).

Methods: One hundred and seventy-nine patients with schizophrenia spectrum disorders and fifty-seven patients with MDD were recruited. Patients were assessed on subjective QOL, self-reported depressive symptoms, illness severity, functioning, and perception of recovery orientation of the service environment (RSA). A multiple linear regression model was used to assess the relationship between QOL and RSA score, controlling for all other factors. Spearman correlation analysis was used to examine the relationship between RSA domains and total QOL in each diagnostic group separately.

Results: The regression model explained 47.4 % of the variance observed in total QOL. Depressive symptoms, functioning and RSA were significantly associated with total QOL in the model. Domains one (life goals) and five (individually tailored services) of the RSA were associated with QOL in both groups. Domains two (patient involvement) and three (diversity of treatment options) were associated with total QOL only in patients with schizophrenia.

Conclusion: Our findings highlight that perceptions of recovery orientation of service, depressive symptoms and functioning significantly affected the subjective QOL of patients with serious mental illness. The differential relationship observed between QOL and domains of RSA in patients with MDD and schizophrenia suggests that targeted interventions meeting the needs of different patient groups may be crucial to improve QOL of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajp.2021.102578DOI Listing
March 2021

The genome of Geosiphon pyriformis reveals ancestral traits linked to the emergence of the arbuscular mycorrhizal symbiosis.

Curr Biol 2021 Apr 15;31(7):1570-1577.e4. Epub 2021 Feb 15.

Department of Biology, University of Ottawa, Ottawa, ON, Canada. Electronic address:

Arbuscular mycorrhizal fungi (AMF) (subphylum Glomeromycotina) are among the most prominent symbionts and form the Arbuscular Mycorrhizal symbiosis (AMS) with over 70% of known land plants. AMS allows plants to efficiently acquire poorly soluble soil nutrients and AMF to receive photosynthetically fixed carbohydrates. This plant-fungus symbiosis dates back more than 400 million years and is thought to be one of the key innovations that allowed the colonization of lands by plants. Genomic and genetic analyses of diverse plant species started to reveal the molecular mechanisms that allowed the evolution of this symbiosis on the host side, but how and when AMS abilities emerged in AMF remain elusive. Comparative phylogenomics could be used to understand the evolution of AMS. However, the availability of genome data covering basal AMF phylogenetic nodes (Archaeosporales, Paraglomerales) is presently based on fragmentary protein coding datasets.Geosiphon pyriformis (Archaeosporales) is the only fungus known to produce endosymbiosis with nitrogen-fixing cyanobacteria (Nostoc punctiforme) presumably representing the ancestral AMF state. Unlike other AMF, it forms long fungal cells ("bladders") that enclose cyanobacteria. Once in the bladder, the cyanobacteria are photosynthetically active and fix nitrogen, receiving inorganic nutrients and water from the fungus. Arguably, G. pyriformis represents an ideal candidate to investigate the origin of AMS and the emergence of a unique endosymbiosis. Here, we aimed to advance knowledge in these questions by sequencing the genome of G. pyriformis, using a re-discovered isolate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2021.01.058DOI Listing
April 2021

Sex differences in symptom severity, cognition and psychosocial functioning among individuals with at-risk mental state for psychosis.

Early Interv Psychiatry 2021 Feb 16. Epub 2021 Feb 16.

Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.

Aim: Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning.

Methods: One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains.

Results: Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning.

Conclusions: This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eip.13131DOI Listing
February 2021

Internalized stigma as an independent predictor of employment status in patients with schizophrenia.

Psychiatr Rehabil J 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong.

Objective: This study aimed to clarify the relationship between employment status and internalized stigma in patients with schizophrenia in Hong Kong.

Methods: One hundred and seventy-nine patients with schizophrenia were included in this study. The employed group included patients with full- or part-time open employment and full-time students. The unemployed group included those attending rehabilitation services and those unemployed. Internalized stigma was assessed using the Internalized Stigma of Mental Illness scale, consisting of alienation, stereotype endorsement, discrimination experience, social withdrawal, and stigma resistance domains. The relationship between these domains and employment status was assessed using logistic regression.

Findings: Fifty-seven percent of participants were employed. Employment status was positively associated with stigma resistance and negatively associated with stereotype endorsement, but not with total internalized stigma.

Conclusions And Implications For Practice: Findings suggest that future interventions can focus on increasing stigma resistance and reducing stereotype endorsement to improve vocational outcomes in patients with schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/prj0000451DOI Listing
February 2021

The predictive power of expressed emotion and its components in relapse of schizophrenia: a meta-analysis and meta-regression.

Psychol Med 2021 Feb 11;51(3):365-375. Epub 2021 Feb 11.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.

Background: Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains.

Methods: Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included.

Results: Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22-7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36-3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16-4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15-0.85)]. None of the moderators included significantly change the results.

Conclusions: These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291721000209DOI Listing
February 2021

Prospective prediction of PTSD and depressive symptoms during social unrest and COVID-19 using a brief online tool.

Psychiatry Res 2021 04 29;298:113773. Epub 2021 Jan 29.

Department of Psychiatry, LKS Faculty of Medicine, University of Hong Kong, Hong Kong. Electronic address:

Large-scale protracted population stressors, such as social unrest and the coronavirus disease 2019 (COVID-19), are associated with increased symptoms of post-traumatic stress disorder (PTSD) and depression. Cost-effective mental health screening is prerequisite for timely intervention. We developed an online tool to identify prospective predictors of PTSD and depressive symptoms in the context of co-occurring social unrest and COVID-19 in Hong Kong. 150 participants completed baseline and follow-up assessments, with a median duration of 29 days. Three logistic regression models were constructed to assess its discriminative power in predicting PTSD and depressive symptoms at one month. Receiver-operating characteristic analysis was performed for each model to determine their optimal decision thresholds. Sensitivity and specificity of the models were 87.1% and 53.8% for probable PTSD, 77.5% and 63.3% for high-risk depressive symptoms, and 44.7% and 96.4% for no significant depressive symptoms. The models performed well in discriminating outcomes (AUCs range: 0.769-0.811). Probable PTSD was predicted by social unrest-related traumatic events, high rumination, and low resilience. Rumination and resilience also predicted high-risk and no significant depressive symptoms, with COVID-19-related events also predicting no significant depression risk. Accessible screening of probable mental health outcomes with good predictive capability may be important for early intervention opportunities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2021.113773DOI Listing
April 2021

Self-referential gaze perception of patients with schizophrenia and its relationship with symptomatology and cognitive functions.

Schizophr Res 2021 Feb 23;228:288-294. Epub 2021 Jan 23.

Department of Psychiatry, The University of Hong Kong, Hong Kong SAR; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR.

Self-referential gaze perception (SRGP)-the perception that others' gaze is towards oneself-is a core experience in patients with schizophrenia, and may be related to common delusional themes such as delusions of reference. Studies exploring SRGP bias in schizophrenia are limited and results have been inconsistent, particularly regarding its relationship with symptomatology and cognition. Seventy-five patients with schizophrenia-spectrum disorders (25 with high level of reference delusion, 25 with low reference delusion and 25 in clinical remission) and 25 matched healthy controls were compared in a gaze perception task to judge whether averted gaze with varied ambiguity was directed at them. All subjects were assessed with delusion and reference ideations and cognitive functions. Psychotic symptoms were assessed in patients. Gaze perception analysis adopted both behavioural and psychophysical approaches. Group differences and predictors of SRGP in ambiguous and unambiguous conditions were investigated. Both groups of symptomatic patients displayed higher ambiguous SRGP rate, and the group with high reference delusions showed more unambiguous SRGP bias. Cognitive functions were negatively associated with SRGP rate while positive and negative symptoms were positively associated. Cognitive function was the only significant predictor for ambiguous-SRGP rate. Patients with psychotic symptoms have hypermentalization of gaze perception as towards oneself, whereas patients with delusions of reference have more profound bias in gaze perception. General cognition is implicated in SRGP rate. Future studies could investigate interventions with targeted psychopathological profiles by improving non-social cognitive functions to test the hypothesis that cognitive functioning is related to SRGP bias and delusional beliefs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2020.12.034DOI Listing
February 2021

Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial.

Lancet 2021 01;397(10271):281-292

Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

Background: The Wee1 (WEE1hu) inhibitor adavosertib and gemcitabine have shown preclinical synergy and promising activity in early phase clinical trials. We aimed to determine the efficacy of this combination in patients with ovarian cancer.

Methods: In this double-blind, randomised, placebo-controlled, phase 2 trial, women with measurable recurrent platinum-resistant or platinum-refractory high-grade serous ovarian cancer were recruited from 11 academic centres in the USA and Canada. Women were eligible if they were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, a life expectancy of more than 3 months, and normal organ and marrow function. Women with ovarian cancer of non-high-grade serous histology were eligible for enrolment in a non-randomised exploratory cohort. Eligible participants with high-grade serous ovarian cancer were randomly assigned (2:1), using block randomisation (block size of three and six) and no stratification, to receive intravenous gemcitabine (1000 mg/m on days 1, 8, and 15) with either oral adavosertib (175 mg) or identical placebo once daily on days 1, 2, 8, 9, 15, and 16, in 28-day cycles until disease progression or unacceptable toxicity. Patients and the team caring for each patient were masked to treatment assignment. The primary endpoint was progression-free survival. The safety and efficacy analysis population comprised all patients who received at least one dose of treatment. The trial is registered with ClinicalTrials.gov, NCT02151292, and is closed to accrual.

Findings: Between Sept 22, 2014, and May 30, 2018, 124 women were enrolled, of whom 99 had high-grade serous ovarian cancer and were randomly assigned to adavosertib plus gemcitabine (65 [66%]) or placebo plus gemcitabine (34 [34%]). 25 women with non-high-grade serous ovarian cancer were enrolled in the exploratory cohort. After randomisation, five patients with high-grade serous ovarian cancer were found to be ineligible (four in the experimental group and one in the control group) and did not receive treatment. Median age for all treated patients (n=119) was 62 years (IQR 54-67). Progression-free survival was longer with adavosertib plus gemcitabine (median 4·6 months [95% CI 3·6-6·4] with adavosertib plus gemcitabine vs 3·0 months [1·8-3·8] with placebo plus gemcitabine; hazard ratio 0·55 [95% CI 0·35-0·90]; log-rank p=0·015). The most frequent grade 3 or worse adverse events were haematological (neutropenia in 38 [62%] of 61 participants in the adavosertib plus gemcitabine group vs ten [30%] of 33 in the placebo plus gemcitabine group; thrombocytopenia in 19 [31%] of 61 in the adavosertib plus gemcitabine group vs two [6%] of 33 in the placebo plus gemcitabine group). There were no treatment-related deaths; two patients (one in each group in the high-grade serous ovarian cancer cohort) died while on study medication (from sepsis in the experimental group and from disease progression in the control group).

Interpretation: The observed clinical efficacy of a Wee1 inhibitor combined with gemcitabine supports ongoing assessment of DNA damage response drugs in high-grade serous ovarian cancer, a TP53-mutated tumour type with high replication stress. This therapeutic approach might be applicable to other tumour types with high replication stress; larger confirmatory studies are required.

Funding: US National Cancer Institute Cancer Therapy Evaluation Program, Ontario Institute for Cancer Research, US Department of Defense, Princess Margaret Cancer Foundation, and AstraZeneca.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)32554-XDOI Listing
January 2021

A Machine Learning Strategy for Drug Discovery Identifies Anti-Schistosomal Small Molecules.

ACS Infect Dis 2021 02 12;7(2):406-420. Epub 2021 Jan 12.

Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0021, United States.

Schistosomiasis is a chronic and painful disease of poverty caused by the flatworm parasite . Drug discovery for antischistosomal compounds predominantly employs whole organism (phenotypic) screens against two developmental stages of , post-infective larvae (somules) and adults. We generated two rule books and associated scoring systems to normalize 3898 phenotypic data points to enable machine learning. The data were used to generate eight Bayesian machine learning models with the Assay Central software according to parasite's developmental stage and experimental time point (≤24, 48, 72, and >72 h). The models helped predict 56 active and nonactive compounds from commercial compound libraries for testing. When these were screened against , the prediction accuracy for active and inactives was 61% and 56% for somules and adults, respectively; also, hit rates were 48% and 34%, respectively, far exceeding the typical 1-2% hit rate for traditional high throughput screens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsinfecdis.0c00754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887754PMC
February 2021

Rare complication of four extremity compartment syndrome requiring fasciotomy from influenza A viral myositis.

BMJ Case Rep 2021 Jan 7;14(1). Epub 2021 Jan 7.

Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, USA.

Influenza A and B commonly cause benign respiratory disease in humans, but can cause more severe illness in high-risk populations. We report an unusual case of a previously healthy adult patient who presented with myositis and severe rhabdomyolysis secondary to influenza A infection that resulted in atraumatic compartment syndrome of all four extremities, each requiring emergent fasciotomy. The patient was subsequently managed with delayed primary closure and skin grafting in the operating room. Prompt recognition of this rare complication by the team resulted in no limb amputations. On his first follow-up appointment, 1 month after discharge, he had regained full functionality in both his hands and his feet were both close to 50% of baseline and improving with physical therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-236893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797313PMC
January 2021

Risk of mortality and complications in patients with schizophrenia and diabetes mellitus: population-based cohort study.

Br J Psychiatry 2021 Jan 7:1-8. Epub 2021 Jan 7.

Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Hong Kong; and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong.

Background: Schizophrenia patients have markedly elevated prevalence of diabetes compared with the general population. However, risk of mortality and diabetes-related complications among schizophrenia patients with co-occurring diabetes is understudied.

Aims: We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes.

Method: This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68 682 patients with incident diabetes only between 2001 and 2016 in Hong Kong using a medical record database of public healthcare services. Association between schizophrenia and all-cause mortality was examined with a Cox proportional hazards model. Effect of schizophrenia on first-year complication occurrence following diabetes diagnosis and post-complication mortality rates were evaluated.

Results: Schizophrenia was associated with increased all-cause mortality (adjusted hazards ratio [aHR] 1.11, 95% CI 1.05-1.18), particularly among men and older age groups. Schizophrenia patients with diabetes had higher metabolic complication rate (aHR 1.99, 95% CI 1.63-2.42), lower microvascular complication rate (aHR 0.75, 95% CI 0.65-0.86) and comparable macrovascular complication rate (aHR 0.93, 95% CI 0.85-1.03), relative to patients with diabetes only. Among patients with diabetes complications, schizophrenia was associated with elevated all-cause mortality after macrovascular (aHR 1.19, 95% CI 1.04-1.37) and microvascular (aHR 1.33, 95% CI 1.08-1.64) complications. Gender-stratified analyses revealed that a significant effect of schizophrenia on heightened post-complication mortality was observed in men only.

Conclusions: Schizophrenia patients with co-occurring diabetes are at increased risk of excess mortality, including post-complication mortality. Further research identifying effective interventions is warranted to optimise diabetes-related outcomes in this vulnerable population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1192/bjp.2020.248DOI Listing
January 2021

The association between migrant status and transition in an ultra-high risk for psychosis population.

Soc Psychiatry Psychiatr Epidemiol 2021 Jan 5. Epub 2021 Jan 5.

Orygen, Melbourne, Australia.

Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder.

Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model.

Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51).

Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00127-020-02012-6DOI Listing
January 2021

ReMind, a smartphone application for psychotic relapse prediction: A longitudinal study protocol.

Early Interv Psychiatry 2020 Dec 23. Epub 2020 Dec 23.

Department of Psychiatry, University of Hong Kong, Hong Kong.

Background: Psychotic disorders are associated with a high rate of relapse. In addition to medication non-adherence, some psychosocial factors have been found to be predictive of relapse (e.g., poor premorbid adjustment, high expressed emotion and substance misuse). Impairments in cognitive functions including general memory functioning, set shifting, attention, processing speed and working memory have also been indicative of a subsequent psychotic episode. As clinical appointments do not always allow for timely or accurate detection of these early warning signs, the ReMind app is developed to explore potential relapse predictors and enhance the process of relapse monitoring.

Aim: The ReMind app aims (1) to assess whether verbal or visual working memory predicts psychotic relapse in 1 year and (2) to determine whether social factors such as stressful life events, level of expressed emotion and medication adherence also predict relapse in 1 year.

Methods: This is a one-year prospective follow-up study involving 176 remitted patients diagnosed with schizophrenia or non-affective psychoses. Monthly relapse predictor assessments will be conducted via ReMind throughout the one-year study duration. These assessments include neurocognitive tasks and psychosocial questionnaires.

Results: Recruitment began in August 2017 and is still ongoing. Preliminary user feedback suggested an overall positive experience with the app.

Conclusion: The ReMind app presents a step forward to the identification and sensitive detection of reliable psychosis relapse predictors. With its anticipated success, it may offer an alternative means of monitoring relapse for the Chinese-speaking population in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eip.13108DOI Listing
December 2020

Mental Health Risks after Repeated Exposure to Multiple Stressful Events during Ongoing Social Unrest and Pandemic in Hong Kong: The Role of Rumination: Risques pour la santé mentale après une exposition répétée à de multiples événements stressants d'agitation sociale durable et de pandémie à Hong Kong: le rôle de la rumination.

Can J Psychiatry 2020 Dec 15:706743720979920. Epub 2020 Dec 15.

Department of Psychiatry, LKS Faculty of Medicine, University of Hong Kong, Hong Kong.

Objectives: The co-occurrence of different classes of population-level stressors, such as social unrest and public health crises, is common in contemporary societies. Yet, few studies explored their combined mental health impact. The aim of this study was to examine the impact of repeated exposure to social unrest-related traumatic events (TEs), coronavirus disease 2019 (COVID-19) pandemic-related events (PEs), and stressful life events (SLEs) on post-traumatic stress disorder (PTSD) and depressive symptoms, and the potential mediating role of event-based rumination (rumination of TEs-related anger, injustice, guilt, and insecurity) between TEs and PTSD symptoms.

Methods: Community members in Hong Kong who had utilized a screening tool for PTSD and depressive symptoms were invited to complete a survey on exposure to stressful events and event-based rumination.

Results: A total of 10,110 individuals completed the survey. Hierarchical regression analysis showed that rumination, TEs, and SLEs were among the significant predictors for PTSD symptoms (all < 0.001), accounting for 32% of the variance. For depression, rumination, SLEs, and PEs were among the significant predictors (all < 0.001), explaining 24.9% of the variance. Two-way analysis of variance of different recent and prior TEs showed significant dose-effect relationships. The effect of recent TEs on PTSD symptoms was potentiated by prior TEs ( = 0.005). COVID-19 PEs and prior TEs additively contributed to PTSD symptoms, with no significant interaction ( = 0.94). Meanwhile, recent TEs were also potentiated by SLEs ( = 0.002). The effects of TEs on PTSD symptoms were mediated by rumination (β = 0.38, standard error = 0.01, 95% confidence interval: 0.36 to 0.41), with 40.4% of the total effect explained. All 4 rumination subtypes were significant mediators.

Conclusions: Prior and ongoing TEs, PEs, and SLEs cumulatively exacerbated PTSD and depressive symptoms. The role of event-based rumination and their interventions should be prioritized for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0706743720979920DOI Listing
December 2020

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

Cancer Med 2021 Jan 9;10(1):199-207. Epub 2020 Dec 9.

Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

Background: Malnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma.

Methods: Patients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre-treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI) <97.5. Skeletal muscle index (SMI) was measured at the L3 level (sarcopenia defined as SMI <34.4 cm /m in women and <45.4 cm /m in men). Patients receiving chemotherapy had NRI and SMI recalculated at the time of first restaging CT.

Results: Of 175 consecutive patients, 33% were malnourished and 39% were sarcopenic at baseline. Patients with pretreatment malnourishment had significantly shorter overall survival (OS; 5.8 vs. 10.9 months, p = 0.000475). Patients who became malnourished during chemotherapy had worse OS compared to those who maintained their nutrition (12.2 vs. 17.5 months p = 0.0484). On univariable analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable analysis, ECOG (p < 0.001), baseline NRI (p = 0.025), and change in NRI during treatment (p < 0.001) were significant poor prognostic factors for OS.

Conclusions: In de novo metastatic GE adenocarcinoma patients, ECOG, pretreatment NRI and change in NRI were significant prognostic factors for OS while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826473PMC
January 2021

The mediating role of knowledge on the contact and stigma of mental illness in Hong Kong.

Int J Soc Psychiatry 2020 Nov 24:20764020975792. Epub 2020 Nov 24.

Department of Social Work and Social Administration, University of Hong Kong, Hong Kong SAR, China.

Background: Although knowledge is a crucial component in contact theory delineating how prejudice changes toward out-groups with stigmatized conditions, little is known about the mediating role of knowledge on contact, stigmatizing attitudes, and behaviors toward mental illness.

Aim: This study aimed to examine the mechanism underlie contact and stigma change by knowledge.

Methods: A total of 366 participants including family members (FM), mental health providers (MHP), and community residents (CR) recruited across communities in Hong Kong and completed measures of contact level, contact quantity, contact quality, mental health related knowledge, prejudice, and discriminatory behaviors. Structural equation modeling was adopted to test the association among the key variables.

Results: Higher level of contact was significantly correlated with better knowledge, less prejudice, and less discriminatory behaviors. Knowledge was directly and negatively correlated with prejudicial attitudes but was not significantly related to discriminatory behaviors. Furthermore, lower levels of prejudice were associated with less discriminatory behaviors.

Conclusion: Enhancement of contact may increase understanding toward people with mental illness (PMI) and diminish stigmatizing attitudes and behaviors. Although prejudicial attitudes may be reduced by broadening mental health knowledge, increasing knowledge only might not ameliorate discriminatory behaviors. Future research should test mediators on contact and stigma by using longitudinal data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0020764020975792DOI Listing
November 2020

Vulnerability and resilience in children during the COVID-19 pandemic.

Eur Child Adolesc Psychiatry 2020 Nov 17. Epub 2020 Nov 17.

The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Background: The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience.

Methods: We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2-12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent-child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic.

Results: The study included 29,202 individual families; of which 12,163 had children aged 2-5 years and 17,029 had children aged 6-12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers.

Conclusions: This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-020-01680-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671186PMC
November 2020

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines.

J Clin Invest 2021 Jan;131(1)

Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium-induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI133371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773399PMC
January 2021

Elucidating the relationship between internalized stigma, cognitive insight, illness severity, and functioning in patients with schizophrenia using a path analysis approach.

J Ment Health 2020 Oct 23:1-10. Epub 2020 Oct 23.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.

Background: There is a paucity of studies examining the interrelationship between internalized stigma, cognitive insight, illness severity, and functioning.

Aims: This study examined the dynamics of the relationship between these factors using a path modelling approach.

Methods: Two hundred and seven patients with schizophrenia spectrum disorders were recruited in this cross-sectional study. Patients were assessed on internalized stigma, cognitive insight (including its two domains, self-reflectiveness and self-certainty), illness severity and functioning. Path analysis was used to test the hypothesized model for the interrelationship between the variables.

Results: A direct positive association was observed between self-certainty and internalized stigma. This was also observed via the paths running through illness severity and functioning. Self-reflectiveness was only associated with self-certainty in the model. The residual variance of internalized stigma in the path model was relatively high.

Conclusion: Our findings highlight that self-certainty is associated with internalized stigma along with illness severity and functioning in individuals with schizophrenia. Therefore, interventions on reduction of internalized stigma may benefit from a multipronged approach targeting self-certainty, illness severity and functioning. The relatively high residual variance of internalized stigma in the model highlights the need for further research to provide better understanding on the mechanisms underlying internalized stigma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09638237.2020.1836553DOI Listing
October 2020

Elucidating the relationship between internalized stigma, cognitive insight, illness severity, and functioning in patients with schizophrenia using a path analysis approach.

J Ment Health 2020 Oct 23:1-10. Epub 2020 Oct 23.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.

Background: There is a paucity of studies examining the interrelationship between internalized stigma, cognitive insight, illness severity, and functioning.

Aims: This study examined the dynamics of the relationship between these factors using a path modelling approach.

Methods: Two hundred and seven patients with schizophrenia spectrum disorders were recruited in this cross-sectional study. Patients were assessed on internalized stigma, cognitive insight (including its two domains, self-reflectiveness and self-certainty), illness severity and functioning. Path analysis was used to test the hypothesized model for the interrelationship between the variables.

Results: A direct positive association was observed between self-certainty and internalized stigma. This was also observed via the paths running through illness severity and functioning. Self-reflectiveness was only associated with self-certainty in the model. The residual variance of internalized stigma in the path model was relatively high.

Conclusion: Our findings highlight that self-certainty is associated with internalized stigma along with illness severity and functioning in individuals with schizophrenia. Therefore, interventions on reduction of internalized stigma may benefit from a multipronged approach targeting self-certainty, illness severity and functioning. The relatively high residual variance of internalized stigma in the model highlights the need for further research to provide better understanding on the mechanisms underlying internalized stigma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09638237.2020.1836553DOI Listing
October 2020

Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer.

Oncology 2021 14;99(1):49-56. Epub 2020 Oct 14.

Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada,

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT.

Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis.

Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2-7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4-8.9) on multivariable and IPTW sensitivity analyses.

Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510446DOI Listing
January 2021

Predictors of Treatment-Resistant and Clozapine-Resistant Schizophrenia: A 12-Year Follow-up Study of First-Episode Schizophrenia-Spectrum Disorders.

Schizophr Bull 2021 Mar;47(2):485-494

Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.

Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbaa145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965066PMC
March 2021

The use of virtual reality for Peri-procedural pain and anxiety at an outpatient spine clinic injection visit: an exploratory controlled randomized trial.

Am J Transl Res 2020 15;12(9):5818-5826. Epub 2020 Sep 15.

Harvard Medical School Boston, MA, USA.

Chronic pain is a major public health problem. There is a need to develop novel treatment strategies to address this growing issue. Virtual reality is emerging as an alternative approach to help people suffering from chronic pain. The purpose of this work was to explore the feasibility, acceptability, and impact of a brief virtual reality relaxation video on peri-procedural pain and anxiety in chronic low back pain patients receiving spinal injections. The intervention was delivered in the context of a busy fluoroscopy injection clinic. Upon arrival to the clinic, consented patients were randomized into one of three groups: (1) Audiovisual monitor-flat screen (AV) (2) Virtual Reality headset (VR) and (3) Control-no intervention. The main questions we set out to answer were: (1) Is it feasible to deliver the intervention in the context of clinical care? (2) Was the intervention acceptable to patients? and (3) Did the intervention impact pain and anxiety surrounding the injection procedure? Viewing a brief relaxation nature video in AV or VR format was not associated with statistically lower pain scores following an injection procedure compared to controls. However, the intervention was associated with lower anxiety scores recorded prior to the injection compared to controls. Importantly, the virtual reality intervention was acceptable and feasible to integrate into a clinic setting, however, to maximize effectiveness, the content delivered to this population should be targeted and delivered over a longer duration. In addition, alternative outcomes and settings beyond peri-procedural pain surrounding an injection should be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540157PMC
September 2020

Excess Mortality and Life-Years Lost in People With Schizophrenia and Other Non-affective Psychoses: An 11-Year Population-Based Cohort Study.

Schizophr Bull 2021 Mar;47(2):474-484

Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.

Psychotic disorders are associated with premature mortality, but research was primarily based on Western countries and rarely examined non-affective psychoses other than schizophrenia (ONAP). This population-based cohort study investigated excess mortality in 46 896 schizophrenia and 20 651 ONAP patients between January 2006 and December 2016 in Hong Kong (HK), by estimating all-cause and cause-specific standardized mortality ratios (SMRs), and life-years lost (LYLs), a recently developed, more precise reduced life expectancy measure taking into account the illness onset (age at first-recorded diagnosis). Changes in mortality metrics over the study period were assessed. Study data were retrieved from a territory-wide medical-record database of public healthcare services to 7.5 million HK residents. Results showed that schizophrenia and ONAP patients had higher all-cause (schizophrenia: SMR: 2.49 [95% CI: 2.43-2.55]; ONAP: 2.00 [1.92-2.09]), natural-cause (1.80 [1.74-1.85]; 1.47 [1.40-1.54]), and unnatural-cause (6.97 [6.47-7.49]; 8.53 [7.61-9.52]) mortality rates than general population. Respiratory diseases, cardiovascular diseases, and cancers accounted for the majority of deaths in patient cohorts. Men and women with schizophrenia had 9.53 years and 8.07 years of excess LYLs, respectively. For ONAP, excess LYLs was 8.18 years for men and 5.44 years for women. The overall mortality gap remained similar for both patient groups over time despite their improved longevity and declined unnatural-cause mortality rates. Taken together, schizophrenia and ONAP are associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to a natural cause. Persistent mortality gap highlights an urgent need for targeted interventions to improve the physical health of patients with psychotic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbaa137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965070PMC
March 2021

Emerging Viral and Bacterial Infections: Within an Era of Opioid Epidemic.

Infect Dis Ther 2020 Dec 11;9(4):737-755. Epub 2020 Sep 11.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, San Diego, CA, USA.

The opioid epidemic is a public health crisis that continues to impact healthcare in the United States of America (USA). While changes in opioid prescribing have curbed the medical use of opioids, the increase in nonmedical use, largely driven by injection drug use (IDU), has contributed to the escalating incidence of opioid use disorder (OUD). Furthermore, IDU is associated with high-risk injection practices that can increase the risk of acquiring viral and bacterial infections. Here in this comprehensive review, we aimed to summarize the epidemiology and management of OUD, along with the screening and antimicrobial treatment of associated infections, specifically focused on human immunodeficiency virus, hepatitis C virus, skin and soft tissue infections, endocarditis, and osteomyelitis. Medication-assisted therapy (MAT) and infection guidelines from the USA will be presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-020-00335-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680496PMC
December 2020

Biomarkers of outcome to weekly paclitaxel in epithelial ovarian cancer.

Gynecol Oncol 2020 11 8;159(2):539-545. Epub 2020 Sep 8.

Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada. Electronic address:

Objective: We sought to evaluate the role of intrinsic chromosomal aberrations in determining favorable outcome to weekly paclitaxel (WP) in patients with epithelial ovarian cancer (EOC).

Methods: We evaluated the common genomic aberrations of two patients with EOC and exceptional WP response in the GENIUS study (NCT03740503). We then searched for potential markers of unusual outcomes to WP in a validation cohort. We performed shallow whole genome sequencing (sWGS) in the tumor tissue of women with EOC considered as short-responders (SR; progression with ≤3 cycles) and long-responders (LR; response at ≥8 cycles) to WP monotherapy.

Results: We identified two women with exceptional response to WP, lasting over four years, who shared chromosome 8 gain as a common genomic aberration. In order to validate our findings, we reviewed 188 patients with EOC treated with WP and selected 61 women (39 SR, 22 LR) with unusual responses. By sWGS, there was no differential alterations in the copy number changes in chromosome 8, or in genes related to angiogenesis, tubulin superfamily, cell-cycle, apoptosis and paclitaxel metabolism or transportation pathways. Amongst the LR group, we identified six exceptionally long responders (ExLR), with responses lasting over a year. In an exploratory analysis, there was increased amplification of angiogenesis (VEGFB, MMP9), tubulin superfamily (TSC2) and apoptosis related genes (BCL2L1, BAD) in ExLR compared to SR. We identified one patient with a complete response to WP for over 7 years. Molecular profiling identified unique amplifications in interleukin related genes (CXCR1, CXCR2, IL1A, IL1B), not detected in other patients.

Conclusion: Intrinsic tumor pathways may impact outcome with weekly paclitaxel monotherapy and further investigations are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.08.032DOI Listing
November 2020