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Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
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.
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.
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.
Quality improvement and patient safety (QIPS) competencies are increasingly important in emergency medicine (EM) and are now included in the CanMEDS framework. We conducted a survey aimed at determining the Canadian EM residents’ perspectives on the level of QIPS education and support available to them.
An electronic survey was distributed to all Canadian EM residents from the Royal College and Family Medicine training streams. The survey consisted of multiple-choice, Likert, and free-text entry questions aimed at understanding familiarity with QIPS, local opportunities for QIPS projects and mentorship, and the desire for further QIPS education and involvement.
Of 535 EM residents, 189 (35.3%) completed the survey, representing all 17 medical schools; 77.2% of respondents were from the Royal College stream; 17.5% of respondents reported that QIPS methodologies were formally taught in their residency program; 54.7% of respondents reported being “somewhat” or “very” familiar with QIPS; 47.2% and 51.5% of respondents reported either “not knowing” or “not having readily available” opportunities for QIPS projects and QIPS mentorship, respectively; 66.9% of respondents indicated a desire for increased QIPS teaching; and 70.4% were interested in becoming involved with QIPS training and initiatives.
Many Canadian EM residents perceive a lack of QIPS educational opportunities and support in their local setting. They are interested in receiving more QIPS education, as well as project and mentorship opportunities. Supporting residents with a robust QIPS educational and mentorship framework may build a cohort of providers who can enhance the local delivery of care.
The completion of a laser safety course remains a core surgical curriculum requirement for otolaryngologists training in the UK. This project aimed to develop a comprehensive laser safety course utilising both technical and non-technical skills simulation.
Otolaryngology trainees and consultants from the West of Scotland Deanery attended a 1-day course comprising lectures, two high-fidelity simulation scenarios and a technical simulation of safe laser use in practice.
The course, and in particular the use of simulation training, received excellent feedback from otolaryngology trainees and consultants who participated. Both simulation scenarios were validated for future use in laser simulation.
The course has been recognised as a laser safety course sufficient for the otolaryngology Certificate of Completion of Training. To the authors’ knowledge, this article represents the first description of using in situ non-technical skills simulation training for teaching laser use in otolaryngology.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Introduction: Quality improvement and patient safety (QIPS) are increasingly recognized as integral to the provision and advancement of emergency medicine (EM) care. In 2015, QIPS were added to the Canadian Medical Education Directives for Specialists (CanMEDS) framework. However, the level of QIPS education and support that Canadian EM residents receive is unknown. In order to better plan national QIPS efforts aimed at enabling EM residents to improve their local care settings, we sought to assess the current state of QIPS education and support in Canadian EM residency programs. Methods: This was a descriptive, cross-sectional electronic survey that was disseminated to all current Canadian EM residents from both Royal College (RC) and Family Medicine - EM training streams. Residents were recruited either directly or through their program's administrative assistant. The survey consisted of multiple-choice, Likert and free-text entry questions. Themes included a) familiarity with QIPS; b) local opportunities for QIPS projects and mentorship; and c) desire for further QIPS education and involvement. The survey was open for a five-week period, with formal reminders after the first and third weeks. Descriptive statistics are reported. Results: 189 (35%) of 535 current EM residents completed the survey, representing all 17 medical schools. 77% of respondents were from the RC stream. 54.7% of respondents reported being “somewhat” or “very” familiar with QIPS. 47.2% of respondents reported “not knowing” or “not having readily available” QIPS projects to participate in their local environment, and 51.5% had equivalent responses with respect to QIPS mentorship opportunities. Only 17.5% of respondents reported that QIPS methodologies were already formally taught in their residency program, and 66.9% indicated a desire for increased QIPS teaching. The majority of respondents were “slightly” (35.9%), “moderately” (23.2%) or “very” (11.3%) interested in becoming involved with QIPS training and initiatives. Conclusion: Responding Canadian EM residents are interested in obtaining greater QIPS education as well as project and mentorship opportunities, but many perceive that they do not have adequate access to these at the current time. As the importance of QIPS increases in the EM community, supporting residents with more robust educational infrastructures may be necessary. Future efforts may include the standardizing of QIPS postgraduate curricula and improving access to QIPS opportunities across the country.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Introduction: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common presentation to the emergency department (ED) accounting for significant morbidity, mortality and health care resource usage. In Alberta, a provincial care pathway was recently developed to provide an evidence informed approach to managing patients with an UGIBs in the ED. Pantoprazole infusions are a commonly used treatment despite evidence that suggests they are generally not indicated prior to endoscopy in the ED. The goal of this project was to optimize management of patients with a NVUGIB, in particular reduce pre-endoscopy pantoprazole infusions. Methods: In July 2016, we implemented a multi-faceted intervention to optimize management of ED patients with NVUGIB including 1. de-emphasizing IV pantoprazole infusions in the ED, 2. clinical decision support (CDS) embedded (for endoscopy, disposition and transfusions) within the order set and 3. educating clinicians about the care pathway. We used a pre/post-order set design, analyzing 391 days pre and 189 days post-order set changes. Data was extracted from our fully integrated electronic health records system. The primary outcome was the % of patients receiving IV pantoprazole infusion ordered by an emergency physician (EP) among all patients with NVUGIB. Secondary outcomes included % transfused with hgb >70g/L and whether using the GIB order set impacted management of NVUGIB patients. Results: In the 391 days pre-order set changes, there were 2165 patients included and in the 189 days post-order set changes, there were 901 patients. For baseline characteristics, patients in the post-order set change group were significantly older (64.4 yrs vs 60.9 yrs p-value=0.0016) and had a lower hgb (115 vs 118, p-value=0.049) but otherwise for gender, measures of severity of illness (systolic blood pressure, heart rate, CTAS, % admitted) there were no significantly differences. For the primary outcome, in the pre-order set phase, 47.1% received a pantoprazole infusion ordered by an EP, compared to 31.5% in the post-order phase, for an absolute reduction of 15.6% (p-value= <0.001). For the secondary outcomes, transfusion rates were similar pre/post (22.08% vs 22.75%). Significant inter-site variability exists with respect to the reduction in pantoprazole infusion rates across the four sites (-23.3% to +6.12%). Conclusion: Our interventions resulted in a significant overall reduction in pantoprazole infusions in ED patients with NVUGIB. Reductions in pantoprazole infusions varied significantly across the different sites, future work in our department will explore and address this variability. Keys to the success of this project included engaging clinicians as well as leveraging the SCM order sets as well as the provincial care pathway. Although there were no changes in transfusion rates, it in unclear if this a function of the CDS not being effective or whether these transfusions were clinically indicated.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Although the pain caused by castration of calves is a significant animal welfare issue for the beef industry, analgesia is not always used for this procedure, largely because of practical limitations associated with injectable forms of pain relief. Novel analgesic formulations have now been developed for livestock to allow topical and buccal administration, offering practical options to improve cattle welfare if shown to be effective. To assess the effects of topical anaesthetic (TA) and buccal meloxicam (BM) on average daily gain (ADG), behaviour and inflammation following surgical castration of beef calves, a total of 50 unweaned bull calves were randomly allocated to: (1) sham castration (SHAM, n=10); (2) surgical castration (C, n=10); (3) surgical castration with pre-operative buccal meloxicam (CBM, n=10); (4) surgical castration with post-operative topical anaesthetic (CTA, n=10); and (5) surgical castration with pre-operative buccal meloxicam and post-operative topical anaesthetic (CBMTA, n=10). Calves were recorded on video for 5 h following treatment and the frequency and duration of specific behaviours displayed by each animal was later observed for 5 min every hour (total of 25 min). Average daily gain was calculated 1, 2 and 6 days following treatment. Scrotal diameter measurements and photographs of wounds were collected from all castrated calves 1, 2 and 6 days following treatment to evaluate inflammation and wound healing. Infrared photographs were used to identify maximum scrotal temperature. Digital photographs were used to visually score wounds on a numerical rating scale of 1 to 5, with signs of inflammation increasing and signs of healing decreasing with progressive scores. Sham castration calves displayed significantly less, and C calves displayed significantly more foot stamps than all other calves (P=0.005). Observations on the duration of time that calves displayed a hypometric ‘stiff gait’ locomotion, indicated that SHAM calves tended to spend no time, C calves tended to spend the greatest time and all other calves tended to spend an intermediate time displaying this behaviour (P=0.06). Maximum scrotal temperatures were lower in CBM and CBMTA calves than C and CTA calves 2 days following treatment (P=0.004). There was no significant effect of treatment on ADG (P=0.7), scrotal diameter (P=0.09) or wound morphology score (P=0.5). These results suggest that TA and BM, alone or in combination, reduced pain and BM reduced inflammation following surgical castration of calves.
Staff training in positive behaviour support (PBS) is a widespread treatment approach for challenging behaviour in adults with intellectual disability.
To evaluate whether such training is clinically effective in reducing challenging behaviour during routine care (trial registration: NCT01680276).
We carried out a multicentre, cluster randomised controlled trial involving 23 community intellectual disability services in England, randomly allocated to manual-assisted staff training in PBS (n = 11) or treatment as usual (TAU, n = 12). Data were collected from 246 adult participants.
No treatment effects were found for the primary outcome (challenging behaviour over 12 months, adjusted mean difference = −2.14, 95% CI: −8.79, 4.51) or secondary outcomes.
Staff training in PBS, as applied in this study, did not reduce challenging behaviour. Further research should tackle implementation issues and endeavour to identify other interventions that can reduce challenging behaviour.
This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention.
This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors.
Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d = 1.37), externalizing (d = 0.85), and posttraumatic stress (d = 1.71), and improvements in well-being (d = 0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility.
This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.