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| 2. |
- Cole, John W, et al.
(author)
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Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke.
- 2018
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Journal article (peer-reviewed)abstract
- Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age<60 years) consisting of 3676 cases and 21118 non-stroke controls from 6 case-control studies. Lastly, we determined if the replicated SNPs also associated with older-onset ischemic stroke in the METASTROKE data-base.Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity.PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.
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| 3. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Mills, Katherine, et al.
(author)
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A randomised controlled trial of integrated psychological therapy for traumatic stress and substance use among adolescents: Trial protocol
- 2020
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In: BMJ Open. - : BMJ. - 2044-6055. ; 10
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Journal article (peer-reviewed)abstract
- Introduction: Post-traumatic stress disorder (PTSD) and substance use disorder frequently co-occur and tend to have their onset during adolescence. Although research has highlighted the importance of treating these disorders in an integrated fashion, there is a dearth of empirically validated integrated treatment options for adolescents with this comorbidity. This paper describes the study protocol for a randomised controlled trial (RCT) examining the efficacy of an integrated trauma-focused cognitive–behavioural treatment for traumatic stress and substance use among adolescents (Concurrent Treatment of PTSD and Substance Use Using Prolonged Exposure - Adolescent (COPE-A)), relative to a supportive counselling control condition (Person-Centred Therapy (PCT)). Methods and analysis: A two-arm, parallel, single-blind RCT with blinded follow-up at 4 and 12 months poststudy entry will be conducted in Sydney, Australia. Participants (n~100 adolescents aged 12–18 years) and their caregivers (caregiver participation is optional) will be allocated to undergo either COPE-A or PCT (allocation ratio 1:1) using minimisation. Both therapies will be delivered individually by project psychologists over a maximum of 16 sessions of 60–90 min duration and will include provision of up to four 30 min optional caregiver sessions. The primary outcome will be between-group differences in change in the severity of PTSD symptoms from baseline to 4-month follow-up, as measured by the Clinician-Administered PTSD Scale for Children and Adolescents for DSM-5. Ethics and dissemination: Ethical approval has been obtained from the human research ethics committees of the Sydney Children’s Hospital Network (HREC/17/SCHN/306) and the University of Sydney (HREC 2018/863). Findings will be published in peer-reviewed journals and presented at scientific conferences. Trial registration number: ACTRN12618000785202; Pre-reults.
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| 5. |
- Mills, Katherine, et al.
(author)
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Comorbidity: Trauma, substance use and mental health
- 2022
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In: Drug and Alcohol Review. - : Wiley. - 0959-5236 .- 1465-3362. ; 41, s. 15-15
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Conference paper (peer-reviewed)abstract
- Substance use and mental health disorders commonly co-occur and they are frequently underpinned by history of psychological trauma. This symposium presents new data on the clinical presentation and documentation of trauma exposure, trauma-related disorders, and their treatment among adults entering substance use treatment, the implementation of integrated trauma-focused therapy in substance use treatment, and presenting issues among adolescents seeking integrated treatment for substance use and traumatic stress.
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| 6. |
- Mills, Katherine, et al.
(author)
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Treating trauma and substance use in adolescents
- 2018. - S3
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In: Drug Alcohol and Review : The official journal of the Australasian Professional Society on Alcohol and other Drugs - The official journal of the Australasian Professional Society on Alcohol and other Drugs. - : Wiley. ; 37, s. 14-14
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Conference paper (peer-reviewed)abstract
- Up to 80% of adolescents have experienced trauma and one‐in‐seven suffer from post‐traumatic stress disorder (PTSD), a chronic, debilitating psychiatric disorder. For 50% of these adolescents, the course of their illness is further complicated by a co‐occurring substance use disorder, which often develops from repeated self‐medication of PTSD symptoms. Once established, both disorders serve to maintain and exacerbate the other leading to extensive social, educational, physical and psychological impairments and a chronic course of illness. It is imperative to intervene early in the trajectory in order to prevent the severe and long lasting burden associated with this common comorbidity. In this presentation we provide an overview of the evidence regarding treatment options available for co‐occurring PTSD and substance use, and promising new early interventions for adolescents. A review of the peer‐reviewed literature regarding treatment of PTSD and substance use was undertaken, and best practice approaches for the treatment of adolescents identified. There is growing evidence for the integrated treatment of PTSD and substance use disorders among adults, but the research pertaining to adolescents is in its infancy. Our current trial examining the efficacy of COPE‐A will provide much needed evidence as to how these conditions may best be treated in adolescence before they become chronic disabling conditions.
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| 7. |
- Mills, Katherine, et al.
(author)
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Trialling exposure-based therapy for adolescent traumatic stress and substance use: Challenges and observations from a randomized controlled trial.
- 2019
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In: European Journal of Psychotraumatology. - : Informa UK Limited. - 2000-8066. ; 10:Sup1, s. 63-63
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Conference paper (peer-reviewed)abstract
- Background: For up to 50% of adolescents experiencing PTSD, the course of their illness is further complicated by co-occurring substance use. Despite this, evidence-based integrated treatment options for adolescents with this comorbidity remain sparse. To address this gap, we are conducting an RCT examining the efficacy of exposure-based therapy for co-occurring PTSD and substance use among adolescents. In this paper, we discuss some of the challenges associated with conducting an RCT in the population group and early observations from the trial. Method: A total of 100 adolescents aged 12–18 years will be recruited. Participants are randomized to receive up to 16 sessions of (i) the integrated exposure-based treatment (COPE-A) or (ii) supportive counselling (control). Blind interviews are conducted at baseline, 4- and 12-months. Substance use and PTSD are measured each therapy session. Results: To date, 20 people have been referred to the study with 17 screened for eligibility. A total of 13 were eligible to participate with nine consented and allocated to a condition. Challenges to trial execution include issues relating to the population group itself, involvement of parents/guardians and other health care providers, logistics, ethical and governance approvals, and resources. Discussion: Although there are significant challenges involved in conducting a trial such as this, they are by no means insurmountable. The study findings will improve our understanding of how to best treat PTSD and substance use during this critical develop-mental period. By intervening early in the trajectory ofthese disorders, it may be possible to prevent thesevere and long-lasting burden associated withcomorbidity across the lifespan.
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| 8. |
- O'Reilly, Kathleen M., et al.
(author)
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Projecting the end of the Zika virus epidemic in Latin America : a modelling analysis
- 2018
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In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
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Journal article (peer-reviewed)abstract
- Background: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries.Methods: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.Results: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.Conclusions: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.
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| 9. |
- Peach, Natalie, et al.
(author)
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Clinical characteristics of adolescents and emerging adults presenting for integrated posttraumatic stress and substance use treatment
- 2024
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In: Advances in Dual Diagnosis. - 1757-0972.
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Journal article (peer-reviewed)abstract
- Adolescence and emerging adulthood are key developmental stages with high risk for trauma exposure and the development of mental and substance use disorders (SUDs). The aim of this study was to compare the clinical profiles of adolescents (aged 12-17 years) and emerging adults (aged 18-25 years) presenting for treatment of posttraumatic stress disorder (PTSD) and SUD. Design/methodology/approach: Data was collected from the baseline assessment of individuals (n = 55) taking part in a randomized controlled trial (RCT) examining the efficacy of an integrated psychological therapy for co-occurring PTSD and SUDs (PTSD+SUD) in young people.Both age groups demonstrated complex and severe clinical profiles, including high frequency trauma exposure, and very poor mental health reflected on measures of PTSD, SUD, suicidality, and domains of social, emotional, behavioral and family functioning. There were few differences in clinical characteristics between the two groups. Similarity between the two groups suggests that the complex problems seen in emerging adults with PTSD+SUD are likely to have had their onset in adolescence or earlier, and to have been present for several years by the time individuals present for treatment. This is the first study to compare the demographic and clinical profiles of adolescents and emerging adults with PTSD+SUD. These findings yield important implications for practice and policy for this vulnerable group. Evidence-based prevention and early intervention approaches and access to care are critical. Alongside trauma-focused treatment, there is a critical need for integrated, trauma-informed approaches specifically tailored to young people with PTSD+SUD.
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| 10. |
- Peach, Natalie, et al.
(author)
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The mental health of adolescents and young people experiencing traumatic stress and problematic substance use.
- 2022
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In: Drug and Alcohol Review. - : Wiley. - 0959-5236 .- 1465-3362. ; 41, s. 16-17
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Conference paper (peer-reviewed)abstract
- Introduction and Aims: Up to 80% of adolescents have experienced trauma and one-in-seven suffer from post traumatic stress disorder (PTSD). For 50% of these adolescents, the course of their illness is further complicated by a co-occurring substance use disorder (SUD). Despite high rates of comorbidity, treatment options remain sparse and there is limited understanding of the clinical profile associated with this comorbidity. We aimed to examine the clinical profile of adolescents seeking treatment for their substance use and traumatic stress.Method: Data were collected as part of a randomised controlled trial examining the efficacy of an integrated psychological treatment for SUD and PTSD among young people aged 12-25 years were assessed for history of trauma, PTSD, substance use and a variety of other domains relating to mental health, social and family functioning and service utilisation.Results: Almost all participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a severe SUD. The most common substances of concern were cannabis and alcohol. All participants experienced multiple traumatic events and >85% met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for PTSD. High levels of clinically elevated depression and anxiety were present in the sample and almost half had a history of attempted suicide.Discussions and Conclusions: Comorbid PTSD and SUD in young people are associated with a complex and severe clinical profile. It is imperative to intervene early in the trajectory in order to prevent the severe and long lasting burden associated with this common comorbidity.
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