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Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1–2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains.
A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics.
One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3–6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1–3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3–6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1–3 months.
This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.
There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs.
We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC).
We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28–1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38–1.50, maternal half-siblings: OR 1.28, 95% CI 1.18–1.39, paternal half-siblings: OR 1.05, 95% CI 0.96–1.15, full cousins: OR 1.06, 95% CI 1.03–1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between −0.09 and 0.12).
Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.
This chapter considers the legacy of respect for individual autonomy and ‘informed consent’ in health research. The primacy of informed consent as a safeguard has led to a systemic regulatory tendency to conceive of and protect privacy as an individual rather than a collective concern. This has limited any regulatory ability to grasp broader social concerns with the use and disclosure of data gathered and generated by health research. Any systemic failure to recognise collective interests in data, and the public interest in (non-personal) data protection, has profound implications for an information age. The chapter reflects on the value of re-negotiating the interests and expectations protected by health research regulation. It recognises the significance of Graeme Laurie’s preferred conception of privacy to enabling such negotiation, and the value of stewardship in establishing normative expectations free of historical encumbrance. Laurie’s conceptualisation of ‘privacy as separateness’, when placed alongside the idea of stewardship, may allow us to rebalance respect to encompass collective interests as fundamental to self-determination and mutual respect.
Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.
This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.
We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.
For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.
We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
There is evidence that autism spectrum disorders (ASDs) co-occur with bipolar disorder (BD) relatively frequently. Individuals with BD often report symptoms of mania and hypomania during adolescence, prior to the age of onset for BD. It is unknown whether these symptoms are associated with ASDs. We examined whether diagnoses of ASDs and autistic traits were associated with hypomania in a large, population-based Swedish twin sample.
Parental structured interviews assessed autistic traits, and were used to assign screening diagnoses of ASDs, when twins were aged 9 or 12 (N = 13 533 pairs). Parents then completed questionnaires assessing hypomania when the twins were aged 15 and 18 (N = 3852 pairs at age 15, and 3013 pairs at age 18). After investigating the phenotypic associations between these measures, we used the classical twin design to test whether genetic and environmental influences on autistic traits influence variation in adolescent hypomania.
Autistic traits and ASD diagnoses in childhood were associated with elevated scores on the measures of adolescent hypomania. Twin analyses indicated that 6–9% of the variance in hypomania was explained by genetic influences that were shared with autistic traits in childhood. When repeating these analyses for specific autistic trait domains, we found a stronger association between social interaction difficulties and hypomania than for other autistic trait domains.
These results indicate a genetic link between autistic traits and hypomania in adolescence. This adds to the growing evidence base of genetic factors associated with ASDs showing links with psychiatric outcomes across childhood and into adulthood.
While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs.
Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males.
In this register-based study, we aimed to test whether female patients who received clinical diagnoses of anxiety, depressive, bipolar and eating disorders are at higher familial risk for ADHD and other neurodevelopmental disorders, compared with diagnosed male patients.
We analysed data from a record-linkage of several Swedish national registers, including 151 025 sibling pairs from 103 941 unique index individuals diagnosed with anxiety, depressive, bipolar or eating disorders, as well as data from 646 948 cousin pairs. We compared the likelihood of having a relative diagnosed with ADHD/neurodevelopmental disorders in index males and females.
Female patients with anxiety disorders were more likely than affected males to have a brother with ADHD (odd ratio (OR) = 1.13, 95% CI 1.05–1.22). Results for broader neurodevelopmental disorders were similar and were driven by ADHD diagnoses. Follow-up analyses revealed similar point estimates for several categories of anxiety disorders, with the strongest effect observed for agoraphobia (OR = 1.64, 95% CI 1.12–2.39). No significant associations were found in individuals with depressive, bipolar or eating disorders, or in cousins.
These results provide modest support for the possibility that familial/genetic risks for ADHD may show gender-specific phenotypic expression. Alternatively, there could be gender-specific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety.
The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).
We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.
The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.
Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown.
We investigated if there is similar etiology in (a) the continuous distribution of the Eating Disorder Inventory-2 (EDI-2), (b) the extremes of EDI-2 score, and (c) registered ED diagnoses, in 1481 female twin pairs at age 18 years (born 1992–1999). EDI-2 scores were self-reported at age 18. ED diagnoses were identified through the Swedish National Patient Register, parent-reported treatment and/or self-reported purging behavior of a frequency and duration consistent with DSM-IV criteria. We differentiated between anorexia nervosa (AN) and other EDs.
The heritability of the EDI-2 score was 0.65 (95% CI 0.61–0.68). The group heritabilities in DeFries–Fulker extremes analyses were consistent over different percentile-based extreme groups [0.59 (95% CI 0.37–0.81) to 0.65 (95% CI 0.55–0.75)]. Similarly, the heritabilities in liability threshold models were consistent over different levels of severity. In joint categorical-continuous models, the twin-based genetic correlation was 0.52 (95% CI 0.39–0.65) between EDI-2 score and diagnoses of other EDs, and 0.26 (95% CI 0.08–0.42) between EDI-2 score and diagnoses of AN. The non-shared environmental correlations were 0.52 (95% CI 0.32–0.70) and 0.60 (95% CI 0.38–0.79), respectively.
Our findings suggest that some EDs can partly be conceptualized as the extreme manifestation of continuously distributed ED features. AN, however, might be more distinctly genetically demarcated from ED features in the general population than other EDs.
Performing an extended Focused Assessment with Sonography in Trauma (eFAST) exam is common practice in the initial assessment of trauma patients. The objective of this study was to systematically review the published literature on diagnostic accuracy of all components of the eFAST exam.
We searched Medline and Embase from inception through October 2018, for diagnostic studies examining the sensitivity and specificity of the eFAST exam. After removal of duplicates, 767 records remained for screening, of which 119 underwent full text review. Meta-DiSc™ software was used to create pooled sensitivities and specificities for included studies. Study quality was assessed using the Quality in Prognostic Studies (QUADAS-2) tool.
Seventy-five studies representing 24,350 patients satisfied our selection criteria. Studies were published between 1989 and 2017. Pooled sensitivities and specificities were calculated for the detection of pneumothorax (69% and 99% respectively), pericardial effusion (91% and 94% respectively), and intra-abdominal free fluid (74% and 98% respectively). Sub-group analysis was completed for detection of intra-abdominal free fluid in hypotensive (sensitivity 74% and specificity 95%), adult normotensive (sensitivity 76% and specificity 98%) and pediatric patients (sensitivity 71% and specificity 95%).
Our systematic review and meta-analysis suggests that e-FAST is a useful bedside tool for ruling in pneumothorax, pericardial effusion, and intra-abdominal free fluid in the trauma setting. Its usefulness as a rule-out tool is not supported by these results.
Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults.
We studied 6866 individuals aged 20–28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components.
At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31–0.36) and with SIC (r = 0.32; 95% CI 0.29–0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35–0.40) than with SIC (r = 0.24; 95% CI 0.21–0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46–0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23–0.43).
We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.
Driving in persons with dementia poses risks that must be counterbalanced with the importance of the care for autonomy and mobility. Physicians often find substantial challenges in the assessment and reporting of driving safety for persons with dementia. This paper describes a driving in dementia decision tool (DD-DT) developed to aid physicians in deciding when to report older drivers with either mild dementia or mild cognitive impairment to local transportation administrators.
A multi-faceted, computerized decision support tool was developed, using a systematic literature and guideline review, expert opinion from an earlier Delphi study, as well as qualitative interviews and focus groups with physicians, caregivers of former drivers with dementia, and transportation administrators. The tool integrates inputs from the physician-user about the patient's clinical and driving history as well as cognitive findings, and it produces a recommendation for reporting to transportation administrators. This recommendation is translated into a customized reporting form for the transportation authority, if applicable, and additional resources are provided for the patient and caregiver.
An innovative approach was needed to develop the DD-DT. The literature and guideline review confirmed the algorithm derived from the earlier Delphi study, and barriers identified in the qualitative research were incorporated into the design of the tool.
Giant ragweed has been increasing as a major weed of row crops in the last
30 yr, but quantitative data regarding its pattern and mechanisms of spread
in crop fields are lacking. To address this gap, we conducted a Web-based
survey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada.
Participants were asked questions regarding giant ragweed and crop
production practices for the county of their choice. Responses were mapped
and correlation analyses were conducted among the responses to determine
factors associated with giant ragweed populations. Respondents rated giant
ragweed as the most or one of the most difficult weeds to manage in 45% of
421 U.S. counties responding, and 57% of responding counties reported giant
ragweed populations with herbicide resistance to acetolactate synthase
inhibitors, glyphosate, or both herbicides. Results suggest that giant
ragweed is increasing in crop fields outward from the east-central U.S. Corn
Belt in most directions. Crop production practices associated with giant
ragweed populations included minimum tillage, continuous soybean, and
multiple-application herbicide programs; ecological factors included giant
ragweed presence in noncrop edge habitats, early and prolonged emergence,
and presence of the seed-burying common earthworm in crop fields. Managing
giant ragweed in noncrop areas could reduce giant ragweed migration from
noncrop habitats into crop fields and slow its spread. Where giant ragweed
is already established in crop fields, including a more diverse combination
of crop species, tillage practices, and herbicide sites of action will be
critical to reduce populations, disrupt emergence patterns, and select
against herbicide-resistant giant ragweed genotypes. Incorporation of a
cereal grain into the crop rotation may help suppress early giant ragweed
emergence and provide chemical or mechanical control options for
late-emerging giant ragweed.
To investigate whether socioeconomic status influenced rates of depot medication prescribing, polypharmacy (more than two psychotropic medications), newer (second-generation) antipsychotic prescribing and clozapine therapy. Postcodes, Scottish Index of Multiple Deprivation (SIMD) categories and current medication status were ascertained. Patients in the most deprived SIMD groups (8–10 combined) were compared with those in the most affluent SIMD groups (1–3 combined).
Overall, 3200 patients with ICD-10 schizophrenia were identified. No clear relationship between socioeconomic status and any of the four prescribing areas was identified, although rates of depot medication use in deprived areas were slightly higher.
Contrary to our hypothesis, there was no evidence that patients with schizophrenia within NHS Greater Glasgow and Clyde who live in more deprived communities had different prescribing experiences from patients living in more affluent areas.
On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed.
Anti-Wolbachia therapy delivers safe macrofilaricidal activity with superior therapeutic outcomes compared to all standard anti-filarial treatments, with the added benefit of substantial improvements in clinical pathology. These outcomes can be achieved, in principle, with existing registered drugs, e.g. doxycycline, that are affordable, available to endemic communities and have well known, albeit population-limiting, safety profiles. The key barriers to using doxycycline as an mass drug administration (MDA) strategy for widespread community-based control are the logistics of a relatively lengthy course of treatment (4–6 weeks) and contraindications in children under eight years and pregnancy. Therefore, the primary goal of the anti-Wolbachia (A·WOL) consortium is to find drugs and regimens that reduce the period of treatment from weeks to days (7 days or less), and to find drugs which would be safe in excluded target populations (pregnancy and children). A secondary goal is to refine regimens of existing antibiotics suitable for a more restricted use, prior to the availability of a regimen that is compatible with MDA usage. For example, for use in the event of the emergence of drug-resistance, in individuals with high loiasis co-infection and at risk of severe adverse events (SAE) to ivermectin, or in post-MDA ‘endgame scenarios’, where test and treat strategies become more cost effective and deliverable.