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This is a copy of the slides presented at the meeting but not formally
written up for the volume.
New biomolecular-inorganic nanohybrids with two different functions, one
from inorganic moiety and the other from biological one were realized by
soft chemical methods such as intercalation, coprecipitation and
exfoliation-reassembling reactions. Recently we have been focusing on
two-dimensional inorganic compounds like layered double hydroxides
(LDHs), since they are biocompatible and can be used as gene or drug
delivery inorganic nanovehicles. To the best of our knowledge, such
inorganic drug delivery vectors are quite different from conventionally
developed ones such as viral based vectors, naked DNA, biodegradable
polymers,liposomes, and etc, those which are however limitedly used due
to their toxicity, immunogenecity, poor integration, and etc. But we
found that such disadvantages can be overcome by immobilizing genes or
drug molecules into these new inorganic vectors, which consist of
non-toxic metal ions with biological compatibility. Since LDHs are anion
exchangeable, negatively charged functional biomolecules can be easily
intercalated into hydroxide layers of LDHs by soft chemical reaction
methods to form bio-LDHs nanohybrids. In such a way they can gain extra
stabilization energy due to the electrostatic interaction between
inorganic layers, whatever they are anionic or cationic, and
counter-charged biomolecules or drugs. We also found that the hydroxide
layers of LDHs could protect the intercalated molecules very efficiently.
If necessary, inorganic materials, as reservoir and delivery carrier, can
be intentionally removed by dissolving them in an acidic or basic media,
which offer a way of recovering the encapsulated biomolecules or drugs.
The possible roles of inorganic lattice as the gene and drug delivery
carrier will be shown by demonstrating the cellular uptake experiments of
FITC, fluorophore, with laser scanning confocal fluorescence microscopy
as well as of radioactive isotope-labeled ATP-LDH hybrid. As the typical
examples for gene and drug delivery systems, As-myc-LDH and MTX-LDH
nanohybrids will be demonstrated along with their endocytic mechanism. In
addition, nanotoxicity of LDH and other inorganic nanoparticles will be
also discussed in detail.
To measure the association between receipt of specific infection prevention interventions and procedure-related cardiac implantable electronic device (CIED) infections.
Retrospective cohort with manually reviewed infection status.
Setting: National, multicenter Veterans Health Administration (VA) cohort.
Sampling of procedures entered into the VA Clinical Assessment Reporting and Tracking-Electrophysiology (CART-EP) database from fiscal years 2008 through 2015.
A sample of procedures entered into the CART-EP database underwent manual review for occurrence of CIED infection and other clinical/procedural variables. The primary outcome was 6-month incidence of CIED infection. Measures of association were calculated using multivariable generalized estimating equations logistic regression.
We identified 101 procedure-related CIED infections among 2,098 procedures (4.8% of reviewed sample). Factors associated with increased odds of infections included (1) wound complications (adjusted odds ratio [aOR], 8.74; 95% confidence interval [CI], 3.16–24.20), (2) revisions including generator changes (aOR, 2.4; 95% CI, 1.59–3.63), (3) an elevated international normalized ratio (INR) >1.5 (aOR, 1.56; 95% CI, 1.12–2.18), and (4) methicillin-resistant Staphylococcus colonization (aOR, 9.56; 95% CI, 1.55–27.77). Clinically effective prevention interventions included preprocedural skin cleaning with chlorhexidine versus other topical agents (aOR, 0.41; 95% CI, 0.22–0.76) and receipt of β-lactam antimicrobial prophylaxis versus vancomycin (aOR, 0.60; 95% CI, 0.37–0.96). The use of mesh pockets and continuation of antimicrobial prophylaxis after skin closure were not associated with reduced infection risk.
These findings regarding the real-world clinical effectiveness of different prevention strategies can be applied to the development of evidence-based protocols and infection prevention guidelines specific to the electrophysiology laboratory.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research.
Introduction: Opioid overdoses (OODs) have become a public health emergency, yet little is known about their long-term outcomes following an OD. We determined the one-year all-cause mortality and associated risk factors in a cohort of patients treated in an urban emergency department (ED) for an OOD. Methods: We reviewed records of all patients who visited St. Paul's Hospital ED from January 2013 to August 2017 and had a discharge diagnosis of OOD or had received naloxone in the ED as per pharmacy records. Patients with a suspected OOD were identified on structured chart review. A patient's first visit for an OOD during the study period was used as the index visit, with subsequent visits excluded. The primary outcome was mortality during the year after the index visit. Mortality was assessed by linking patient electronic medical records with Vital Statistics data. Deaths that occurred in the ED on the index visit were excluded. Patients admitted to hospital following ED treatment were included in this study. We described patient characteristics, calculated mortality rates, and used Cox regression to identify risk factors. Results: A total of 2239 patients visited the ED for an OOD during the study period, with a median patient age of 37 years (IQR 29, 49). Males comprised 73% of patients, while 28% had no fixed address, and 21% received take-home naloxone at the index visit. In total, 137 patients (6.1%) died within 1 year of the index visit. Eighty-one deaths (3.6%) occurred within 6 months, including 24 deaths (1.1%) that occurred within 1 month. The highest mortality rate occurred in 2017, with 8.0% of patients entering the cohort that year dying within 1 year. Gender did not significantly impact mortality risk. A Cox regression analysis controlled for gender, housing status, and whether take-home naloxone was provided at the index visit indicated that advancing age (adjusted hazards ratio [AHR] 1.03; 95%CI: 1.01-1.04 for each year increase in age) and the index visit calendar year (AHR 1.30; 95%CI: 1.10-1.54 for each yearly increase in the study period) were significant factors for mortality within 1 year. Conclusion: The mortality rate following an opioid OD treated in the ED is high, with over 6% of patients in our study dying within 1 year. The rising mortality risk with increasing calendar year may reflect the growing harms of fentanyl-related OODs. Patients visiting the ED for an OOD should be considered high risk and offered preventative treatment and referrals prior to discharge.
Introduction: September 2017 saw the launch of the British Columbia (BC) Emergency Medicine Network (EM Network), an innovative clinical network established to improve emergency care across the province. The intent of the EM Network is to support the delivery of evidence-informed, patient-centered care in all 108 Emergency Departments and Diagnostic & Treatment Centres in BC. After one year, the Network undertook a formative evaluation to guide its growth. Our objective is to describe the evaluation approach and early findings. Methods: The EM Network was evaluated on three levels: member demographics, online engagement and member perceptions of value and progress. For member demographics and online engagement, data were captured from member registration information on the Network's website, Google Analytics and Twitter Analytics. Membership feedback was sought through an online survey using a social network analysis tool, PARTNER (Program to Analyze, Record, and Track Networks to Enhance Relationships), and semi-structured individual interviews. This framework was developed based on literature recommendations in collaboration with Network members, including patient representatives. Results: There are currently 622 EM Network members from an eligible denominator of approximately 1400 physicians (44%). Seventy-three percent of the Emergency Departments and Diagnostic and Treatment Centres in BC currently have Network members, and since launch, the EM Network website has been accessed by 11,154 unique IP addresses. Online discussion forum use is low but growing, and Twitter following is high. There are currently 550 Twitter followers and an average of 27 ‘mentions’ of the Network by Twitter users per month. Member feedback through the survey and individual interviews indicates that the Network is respected and credible, but many remain unaware of its purpose and offerings. Conclusion: Our findings underscore that early evaluation is useful to identify development needs, and for the Network this includes increasing awareness and online dialogue. However, our results must be interpreted cautiously in such a young Network, and thus, we intend to re-evaluate regularly. Specific action recommendations from this baseline evaluation include: increasing face-to-face visits of targeted communities; maintaining or accelerating communication strategies to increase engagement; and providing new techniques that encourage member contributions in order to grow and improve content.
Chronic maxillary atelectasis is a rare and underdiagnosed condition in which there is a persistent and progressive decrease in maxillary sinus volume secondary to inward bowing of the antral walls. Chronic maxillary atelectasis is typically unilateral. Simultaneous bilateral chronic maxillary atelectasis is extremely uncommon.
A retrospective review was performed of patient data collected by the senior clinician over a three-year period (2015–2018). A comprehensive literature search was conducted to locate all documented cases of chronic maxillary atelectasis in English-language literature. Abstracts and full-text articles were reviewed.
Three patients presented with sinonasal symptoms. Imaging findings were consistent with bilateral chronic maxillary atelectasis. The literature review revealed at least nine other cases of bilateral chronic maxillary atelectasis. Management is typically via endoscopic middle meatus antrostomy.
Chronic maxillary atelectasis was initially defined as a unilateral disorder, but this description has been challenged by reports of bilateral cases. Further investigation is required to determine the aetiology and pathophysiology of the disease.
OBJECTIVES/SPECIFIC AIMS: Reducing radiologic exams has been a focus of cost reduction in healthcare systems. The utility and justification of obtaining cross-sectional imaging (PPCSI) before surgical intervention continues to be evaluated. For peripheral artery disease (PAD) consensus guidelines regarding PPCSI do not exist and may be influenced by patient complexity, variation of disease presentation, and physician preference. The objective of this study was to determine the utility of PPCSI before percutaneous PAD intervention. METHODS/STUDY POPULATION: Patients receiving first-time endovascular revascularization procedure for PAD from 2013 to 2015 were evaluated for PPCSI done within 180 days prior to revascularization. Patient and physician demographics, perioperative characteristics, and disease distribution/severity were evaluated. The primary outcome was technical success defined as improving inflow and/or revascularization of the target outflow vessels to <50% stenosis. RESULTS/ANTICIPATED RESULTS: Of the 348 patients who underwent an attempted revascularization procedure 159 (45.7%) patients underwent PPCSI, including 151 CTA and 8 MRA. Of these, 48% were ordered by the referring provider (84% at an outside institution), and 52% were ordered by the treating physician. PPCSI was performed a median of 26 days (IQR 9-53) prior to procedure. Individual vascular surgeon practice identified PPCSI rates ranging from 31% to 70%. On multivariate analysis chronic kidney disease (OR=0.35; CI 0.17–0.73) had the strongest effect against of PPCSI, and Inpatient/ED evaluation (OR=3.20; CI 1.58–6.50), aorto-iliac (OR=2.78; CI 1.46–5.29) and femoral-popliteal occlusions (OR=2.51; CI 1.38–4.55) most strongly predicted PPCSI. After excluding 31 diagnostic procedures, technical success did not differ between endovascular procedures with PPSCI (91.3%) or without PPCSI (85.6%), p=0.11. When analyzing 89 femoral-popliteal occlusions, technical success was higher with PPCSI (88%) compared to procedures without PPSCI (69%), p=0.026. DISCUSSION/SIGNIFICANCE OF IMPACT: PPCSI use is influenced by inpatient status, chronic kidney disease, and anatomic consideration. PPCSI was not associated with overall technical success although it appeared beneficial for femoral-popliteal occlusions. Routine practices of ordering of PPCSI may not be warranted when considering technical success but may be important in treatment planning. Further studies are warranted to determine if radiation, cost, and contrast load justify PPCSI.
While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.
In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.
Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.
Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.
Introduction: In many rural and remote communities in BC, family physicians who are providing excellent primary and emergency care would like to access useful, timely, and collegial support to ensure the highest quality of health services for their patients. We undertook a real-time virtual support project in Robson Valley, located in northern BC, to evaluate the use of digital technologies such as videoconferencing for on demand consultation between family physicians at rural sites and emergency physicians at a regional site. Telehealth consults also occurred between rural sites with nurses at community emergency rooms consulting with local on-call physicians. Our aim was to use telehealth to facilitate timely access to high quality, comprehensive, coordinated team-based care. An evaluation framework, based on the Triple Aim sought to: 1) Identify telehealth use cases and assess impact on patient outcomes, patient and health professional experience, and cost of health care delivery; and 2) Assess the role of relationships among care team members in progressing from uptake to normalization of telehealth into routine usage. Methods: Using a participatory approach, all members of the pilot project were involved in shaping the pilot including the co-development of the evaluation itself. Evaluation was used iteratively throughout implementation for ongoing quality improvement via regular team meetings, sharing and reflecting on findings, and adjusting processes as required. Mixed methods were used including: interviews with family physicians, nurses, and patients at rural sites, and emergency physicians at regional site; review of records such as technology use statistics; and stakeholder focus groups. Results: From November 2016 to July 2017, 26 cases of telehealth use were captured and evaluated. Findings indicate that telehealth has positively impacted care team, patients, and health system. Benefits for care team at the rural sites included confidence in diagnoses through timely access to advice and support, while emergency physicians at the regional site gained deeper understanding of the practice settings of rural colleagues. Nevertheless, telehealth has complicated the emergency department work flow and increased physician workload. Findings demonstrated efficiencies for the health system, including reducing the need for patient transfer. Patients expressed confidence in the physicians and telehealth system; by receiving care closer to home, they experienced personal cost savings. Implementation saw a move away from scheduled telehealth visits to real use of technology for timely access. Conclusion: Evidence of the benefits of telehealth in emergency settings is needed to support stakeholder engagement to address issues of workflow and capacity. This pilot has early indications of significant local impact and will inform the expansion of emergency telehealth in all emergency settings in BC.
Introduction: Patients with Heart failure (HF) experience frequent decompensation necessitating multiple emergency department (ED) visits and hospitalizations. If patients are able to receive timely interventions and optimize self-management, recurrent ED visits may be reduced. In this feasibility study, we piloted the application of home telemonitoring to support the discharge of HF patients from hospital to home. We hypothesized that TEC4Home would decrease ED revisits and hospital admissions and improve patient health outcomes. Methods: Upon discharge from the ED or hospital, patients with HF received a blood pressure cuff, weight scale, pulse oximeter, and a touchscreen tablet. Participants submitted measurements and answered questions on the tablet about their HF symptoms daily for 60 days. Data were reviewed by a monitoring nurse. From November 2016 to July 2017, 69 participants were recruited from Vancouver General Hospital (VGH), St. Pauls Hospital (SPH) and Kelowna General Hospital (KGH). Participants completed pre-surveys at enrollement and post-surveys 30 days after monitoring finished. Administrative data related to ED visits and hospital admissions were reviewed. Interviews were conducted with the monitoring nurses to assess the impact of monitoring on patient health outcomes. Results: A preliminary analysis was conducted on a subsample of participants (n=22) enrolled across all 3 sites by March 31, 2017. At VGH and SPH (n=14), 25% fewer patients required an ED visit in the post-survey reporting compared to pre-survey. During the monitoring period, the monitoring nurse observed seven likely avoided ED admissions due to early intervention. In total, admissions were reduced by 20% and total hospital length of stay reduced by 69%. At KGH (n=8), 43% fewer patients required an ED visit in the post-survey reporting compared to the pre-survey. Hospital admissions were reduced by 20% and total hospital length of stay reduced by 50%. Overall, TEC4Home participants from all sites showed a significant improvement in health-related quality of life and in self-care behaviour pre- to 90 days post-monitoring. A full analysis of the 69 patients will be complete in February 2018. Conclusion: Preliminary findings indicate that home telemonitoring for HF patients can decrease ED revisits and improve patient experience. The length of stay data may also suggest the potential for early discharge of ED patients with home telemonitoring to avoid or reduce hospitalization. A stepped-wedge randomized controlled trial of TEC4Home in 22 BC communities will be conducted in 2018 to generate evidence and scale up the service in urban, regional and rural communities. This work is submitted on behalf of the TEC4Home Healthcare Innovation Community.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Fruit producers in the Eastern United States face a wide range of weather-related risks that have the capacity to largely impact yields and profitability. This research examines the economic implications associated with responding to these risks for sweet cherry production in three different systems: high tunnels, revenue insurance, and weather insurance. The analysis considers a distribution of revenue flows and costs using detailed price, yield, and weather data between 1984 and 2013. Our results show that the high tunnel system generates the largest net return if significant price premiums exist for earlier and larger fruit.