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A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.
A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).
Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.
Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.
This article examines provincial policy influence on long-term care (LTC) professionals’ advice-seeking networks in Canada’s Maritime provinces. The effects of facility ownership, geography, and region-specific political landscapes on LTC best-practice dissemination are examined. We used sociometric statistics and network sociograms, calculated from surveys with 169 senior leaders in LTC facilities, to identify advice-seeking network structures and to select 11 follow-up interview participants. Network structures were distinguished by density, sub-group number, opinion leader, and boundary spanner distribution. Network structure was affected by ownership model in Nova Scotia and Prince Edward Island, and by regional geography in New Brunswick. Political instability within each province’s LTC system negatively affected network actors’ capabilities to enact innovation. Moreover, provincial policy variations influence advice-seeking network structures, facilitating and constraining relationship development and networking. Consequently, local policy context is essential to informing dissemination strategy design or implementation.
Over the past twenty years, several taxonomies of personality and psychopathology have been developed. More recently, many studies have compared dimensional models of personality pathology to categorical diagnoses of personality disorders. Altogether, this proliferation of research suggests the value of articulating the desirable properties of a good taxonomic system. Here, the authors extend basic research in cognitive science on the limitations of representational capacity, which suggests that humans need to compress complex clinical presentations to make good judgments. With this in mind, the authors propose that information compression and information fidelity are two principles that are essential to good taxonomy. The principle of information compression is that taxonomies should prune the complexities of a detailed clinical presentation to focus on important sources of covariation. The principle of information fidelity is that a good taxonomy should maintain essential features that reasonably approximate the structure of an individual or the population. They conclude with the claim that the overarching goal of taxonomic science in classifying personality pathology is to provide clinicians and researchers with empirically based informative priors that help to bias thinking toward useful clinical distinctions.
Innovation Concept: A major barrier to the development of a national simulation case repository and multi-site simulation research is the lack of a standardized national case template. This issue was recently identified as a priority research topic for Canadian simulation based education (SBE) research in emergency medicine (EM). We partnered with the EM Simulation Education Researchers Collaborative (EM-SERC) to develop a national simulation template. Methods: The EM Sim Cases template was chosen as a starting point for the consensus process. We generated feedback on the template using a three-phase modified nominal group technique. Members of the EM-SERC mailing list were consulted, which included 20 EM simulation educators from every Canadian medical school except Northern Ontario School of Medicine and Memorial University. When comments conflicted, the sentiment with more comments in favour was incorporated. Curriculum, Tool or Material: In phase one we sought free-text feedback on the EM Sim Cases template via email. We received 65 comments from 11 respondents. An inductive thematic analysis identified four major themes (formatting, objectives, debriefing, and assessment tools). In phase two we sought free-text feedback on the revised template via email. A second thematic analysis on 40 comments from 12 respondents identified three broad themes (formatting, objectives, and debriefing). In phase three we sought feedback on the penultimate template via focus groups with simulation educators and technologists at multiple Canadian universities. This phase generated 98 specific comments which were grouped according to the section of the template being discussed and used to develop the final template (posted on emsimcases.com). Conclusion: We describe a national consensus-building process which resulted in a simulation case template endorsed by simulation educators from across Canada. This template has the potential to: 1. Reduce the replication of effort across sites by facilitating the sharing of simulation cases. 2. Enable national collaboration on the development of both simulation cases and curricula. 3. Facilitate multi centre simulation-based research by removing confounders related to the local adoption of an unfamiliar case template. This could improve the rigour and validity of these studies by reducing inter-site variability. 4. Increase the validity of any simulation scenarios developed for use in national high-stakes assessment.
Introduction: One of the most common adverse effects of habitual cannabis use is hyperemesis—recurrent bouts of protracted vomiting, retching and abdominal pain superimposed on a baseline of daily nausea and anorexia. Largely anecdotal evidence supports the use of haloperidol, benzodiazepines or topical capsaicin over traditional antiemetics, yet little is known about the cause or optimal treatment of this newly recognized disorder. We report the results of one of the first clinical trials on so-called cannabis hyperemesis syndrome (NCT03056482). Methods: We approached adults with a working diagnosis of hyperemesis due to cannabis, provided they had ongoing emesis for >2 hours, a cyclic pattern of 3+ episodes in the last 2 years, and near daily use of cannabis by inhalation. We excluded those who were pregnant, deemed unreliable, or using opioids. Subjects provided written consent to be randomized during the index or any subsequent visit to either haloperidol (with a nested randomization to either 0.05 mg/kg or 0.1 mg/kg) or ondansetron 8 mg intravenously in a quadruple-blind fashion, and to be followed for 7 days. The primary outcome was the average reduction from baseline in abdominal pain and nausea (each measured on a 10-cm VAS) at 2 hours. While the original trial design allowed for crossover, the primary analysis used only the first treatment period since fewer than the prespecified threshold of 20% of subjects crossed over. Results: We enrolled 33 subjects, of whom 30 (16 men, 29+/-11 years old, using 1.5+/-0.9 g/day since age 19+/-2 years) were treated at least once (haloperidol 13, ondansetron 17). Haloperidol at either dose was superior to ondansetron (difference 2.3 cm [95%CI 0.6, 4.0]; p = 0.01), with similar improvements in both pain and nausea, as well as less rescue antiemetics (27% vs 61%; p = 0.04), and shorter time to ED departure (3.1+/-1.7 vs 5.6+/-4.5 hours; p = 0.03 Wilcoxon rank sum). There were two (haloperidol) vs six (ondansetron) return visits for ongoing nausea/vomiting, as well as two return visits for acute dystonia, both in the higher dose haloperidol group. Conclusion: Haloperidol is superior to ondansetron for the acute symptomatic treatment of patients with ongoing hyperemesis attributed to habitual cannabis use. The efficacy of this agent over ondansetron provides insight into the mechanism of this new disorder, now almost a daily diagnosis in many Canadian emergency departments.
Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status. We prospectively examined the effects of depressive symptoms, assessed in 2002-2004, on all-cause and cardiovascular -mortality in a large sample of 5936 middle-aged participants, with and without established CHD, followed over 5.6 years
We created 4-risk-factor groups based on the cross classification of depressive symptoms and CHD status. The age-and-sex-adjusted hazard ratios for all causes death were 1.67-fold (p< 0.05) higher for participants with only CHD, 2.10-fold (p< 0.001) higher for those with only depressive symptoms and 4.99-fold (p< 0.001) higher for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. Further comparisons indicated that the risks of all-cause death were also higher, but to a lesser extent, for participants with both depressive-symptoms and CHD when compared to those with only one of these conditions. These associations were also observed for cardiovascular mortality
This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and CVD death and that this risk is particularly marked in depressive participants with co-morbid CHD. Several clinical guidelines have recommended screening, referral, and treatment of depression in primary and cardiovascular care units. These findings suggest that these recommendations need further consideration.
Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects.
To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design.
We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed.
Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex.
Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.
Postpartum onset of anxiety disorders, particularly of obsessive-compulsive disorder (OCD) are rarely reported in the literature although frequently observed in the clinical setting. The obsessions and compulsions focus on the newborn and create immense distress. Research on the stress response in postpartum psychiatric populations is limited and the neural and neuroendocrine correlates of postpartum OCD is unclear. Few studies investigated the brain circuitry involved in OCD, very few included women and none in the postpartum period, and none of which focus on the stress reactivity underlying network.
The purpose of this study is to examine neural activation in women with postpartum OCD as compared to healthy postpartum women in response to a stress task using functional magnetic resonance imaging (fMRI).
Subjects are females diagnosed with postpartum OCD and matched healthy controls. During the stress phase, fMRI is recorded to observe brain activity while subjects complete the Montreal Imaging Stress Task (MIST), a psychological stressor. Saliva samples are obtained before and after the stressor to assess the hormonal stress response along with subjective stress rating.
To date, 9 postpartum OCD women and 10 controls completed the study. Preliminary analyses show that the majority of the subjects demonstrated an increase in subjective stress rating with postpartum OCD women experiencing the MIST more stressful compared to controls. As previously reported we observed deactivation throughout the limbic system in all subjects but only the postpartum OCD women also recruited the orbitofrontal cortex.
These preliminary observations are consistent with the literature and point toward a distinct stress brain activation pattern in postpartum OCD women. It is hoped that the results of this study will provide further insight into the nature of neurophysiological and neuroendocrinological involvement in postpartum OCD.
There is strong qualitative and quantitative evidence of white matter abnormalities in schizophrenia and bipolar disorder from structural magnetic resonance imaging (MRI). There is also good evidence of altered connectivity in schizophrenia using diffusion tensor magnetic resonance imaging, but no study has yet addressed the diagnostic specificity of these findings or whether they are related to specific susceptibility genes.
Diffusion tensor MRI was used to assess white matter integrity in patients with bipolar I disorder (BD) (n=42), schizophrenia (n=28) and healthy controls (n=38). Clinically stable patients with one other close family member with the same diagnosis were selected. In a second study, we examined white matter associations with Neuregulin I in a sample of healthy controls. Fractional anisotropy (FA) was compared between the groups using voxel-based morphometry, automated region of interest analysis and probabilistic tractography. Results : Patients with BD and those with schizophrenia showed reduced FA in the anterior limb of the internal capsule, anterior thalamic radiation and uncinate fasciculus compared with controls. Results from the second study showed reductions in those carrying a Neuregulin 1 variant previously associated with psychotic symptoms.
Reduced white matter density and integrity is common to both schizophrenia and BD. It is likely that this shared white matter disruption is determined in part by shared genetic risk factors.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
Psychiatric comorbidities and alcohol craving are known contributors to differences in alcohol consumption patterns.
Univariate and multivariable linear regression models were used to examine the association and interactions between the Inventory of Drug Taking Situations (IDTS) negative, positive and temptation sub-scale scores, sex, as well as co-morbid depression and anxiety determined by Psychiatric Research Interview of Substance and Mood Disorders (PRISM) with alcohol consumption measured by Time Line Follow Back (TLFB) during preceding 90 days in 287 males and 156 females meeting DSM-IV criteria for alcohol dependence.
IDTS positive, negative and temptation scores were strongly associated with increased alcohol consumption measures including the number of drinks per day and number of drinking days per week (P < 0.0001). Male sex was associated with higher amount of alcohol consumption per drinking day (P < 0.001), but not with the number of drinking days per week (P > 0.05). In men, lifetime history of depression was associated with fewer drinking days (P = 0.0084) and fewer hazardous drinking days (P = 0.0214) but not with differences in daily alcohol consumption. In women, depression history was not significantly associated with alcohol consumption measures. Post-hoc sex-stratified analyses suggested that the association of the negative IDTS score with total amount of alcohol consumed by men may be modified (decreased) by lifetime depression history. We found no associations of alcohol consumption measures with anxiety or substance-induced depression.
Decreased frequency of drinking in male alcoholics with lifetime depression history is unexpected. This finding emphasizes the complex relationships between alcoholism and depression, which require further investigation.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Equal access to health care treatment is a highly prioritized goal in most OECD countries. Timely access has become a priority too; in Denmark now with a 4-week deadline from referral to diagnosis. When mental health services become more centralized and allocation of patients to treatment further away from home become more common, it could have a negative impact on the goal of equal access.
To determine the impact of socioeconomic position (SEP) and distance to provider on outpatient mental health care utilization among incident users of antidepressants.
A nationwide, Danish, register based, follow-up study on frequencies of contacts to out-patient psychiatric services, psychologist consultations supported by public funding and therapeutic talks by general practice.
Outpatient-psychiatric services were reached more often by patients in low SEP measured by income, but their frequencies of visits were less. Contacts to psychologists were less than half for patients in low SEP and less frequent too. Mental health service by GP showed low SEP associated with low contact. No difference in use of emergency or inpatient psychiatric services was found. Distance to provider showed interaction with SEP and contact to psychologist and frequencies of contact to outpatient psychiatrists. When distance increased by 5 km, contact to psychologist fell by 11% among lowest income group and frequencies of visits to outpatient psychiatrist fell by 5%.
Lower SEP is associated with lower mental health care utilization. Increased distance to provider increases inequity in mental health service utilization.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The national implementation of competency-based medical education (CBME) has prompted an increased interest in identifying and tracking clinical and educational outcomes for emergency medicine training programs. For the 2019 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, we developed recommendations for measuring outcomes in emergency medicine training in the context of CBME to assist educational leaders and systems designers in program evaluation.
We conducted a three-phase study to generate educational and clinical outcomes for emergency medicine (EM) education in Canada. First, we elicited expert and community perspectives on the best educational and clinical outcomes through a structured consultation process using a targeted online survey. We then qualitatively analyzed these responses to generate a list of suggested outcomes. Last, we presented these outcomes to a diverse assembly of educators, trainees, and clinicians at the CAEP Academic Symposium for feedback and endorsement through a voting process.
Academic Symposium attendees endorsed the measurement and linkage of CBME educational and clinical outcomes. Twenty-five outcomes (15 educational, 10 clinical) were derived from the qualitative analysis of the survey results and the most important short- and long-term outcomes (both educational and clinical) were identified. These outcomes can be used to help measure the impact of CBME on the practice of Emergency Medicine in Canada to ensure that it meets both trainee and patient needs.
This report updates the incidence of herbicide-resistant (HR) weeds across western Canada from the last report covering 2007 to 2011. This third round of preharvest surveys was conducted in Saskatchewan in 2014 and 2015, Manitoba in 2016, and Alberta in 2017, totaling 798 randomly selected cropped fields across 28 million ha. In addition, we screened 1,108 weed seed samples submitted by prairie growers or industry between 2012 and 2016. Of 578 fields where wild oat seed was collected, 398 (69%) had an HR biotype: 62% acetyl-CoA carboxylase inhibitor (WSSA Group 1) resistant, 34% acetolactate synthase inhibitor (Group 2) resistant, and 27% Group 1+2 resistant (vs. 41%, 12%, and 8%, respectively, in the previous second-round surveys from 2007 to 2009). The sharp increase in Group 2 resistance is the result of reliance on this site of action to manage Group 1 resistance and the resultant increased selection pressure. There are no POST options to control Group 1+2–HR wild oat in wheat or barley. The rise of Group 2 resistance in green foxtail (11% of sampled fields) and yellow foxtail (17% of Manitoba fields), which was not detected in the previous survey round, parallels the results for wild oat resistance. Various Group 2–HR populations of broadleaf weeds were confirmed, with cleavers and field pennycress being most abundant. Results of submission-sample testing reflected survey results. Although not included in this study, a postharvest survey in Alberta in 2017 indicated widespread Groups 2, 4 (dicamba), and 9 (glyphosate) resistance in kochia and Group 2 resistance in Russian thistle. These surveys bring greater awareness of HR weeds to growers and land managers at local and regional levels, and highlight the urgency to preserve herbicide susceptibility in our key economic weed species.
The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology.
169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02–14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89–14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ.
The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = −0.18, p = 0.021) and autism spectrum disorder trait (β = −0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = −0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores.
The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.
The impact of hurricanes on emergency services is well-known. Recent history demonstrates the need for prehospital and emergency department coordination to serve communities during evacuation, storm duration, and cleanup. The use of telehealth applications may enhance this coordination while lessening the impact on health-care systems. These applications can address triage, stabilization, and diversion and may be provided in collaboration with state and local emergency management operations through various shelters, as well as during other emergency medical responses.