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The Repugnant Conclusion is an implication of some approaches to population ethics. It states, in Derek Parfit's original formulation,
For any possible population of at least ten billion people, all with a very high quality of life, there must be some much larger imaginable population whose existence, if other things are equal, would be better, even though its members have lives that are barely worth living. (Parfit 1984: 388)
ABSTRACT IMPACT: Analyzing the types of technical assistance (basic, targeted or intensive) provided by the Opioid Response Network (ORN) to unique and hard-to-reach populations (UHRP) informs addiction health services and translational research by identifying technical assistance needs in these populations which may require a higher level of intensity. OBJECTIVES/GOALS: To improve ORN dissemination and implementation efforts, the project classifies TA requests into one of three categories: basic, targeted, and intensive. This TA Framework assists the ORN project team in understanding the level of TA required in the delivery of evidence-based practices to address opioids with communities with respect to UHRP. METHODS/STUDY POPULATION: TA requests from April 1, 2019, to April 1, 2020, were selected. The ORN classifies TA requests in one of three categories: basic (dissemination & brief consultation), targeted (services to enhance readiness and capacity), and intensive (full incorporation of innovation considering context, culture, and linguistics) (Fixsen, et. al., 2009; Becker, et al., 2020). Unique and hard-to-reach populations (UHRP) are defined based on physical location (i.e., remote or isolated), social position, or other vulnerabilities (i.e. member of an ethnic or racial minority group) (Thurman, & Harrison, 2020). ORN classifies 26 types of UHRP these types are not mutually exclusive. A frequency analysis of the UHRP types was conducted. Bivariate correlations between UHRP types that had a minimum of 30 cases were performed. RESULTS/ANTICIPATED RESULTS: Among 746 TA requests selected, 226 had missing information about UHRP types and 29 had missing information TA levels. These requests were excluded from the frequency analysis. The three most common UHRP types were people living in rural or remote areas (n=262, 50%), people who are uninsured or underinsured (n=162, 31%), and people who inject drugs (n=158, 30%). Most TA requests were targeted (69%), 23% were intensive, and 9% were basic. Bivariate correlations were performed between 21 UHRP types. Moderate (Pearson’s r=0.4-0.6) or strong correlations (r>0.6) were found for 11 occurrences for the UHRP type of ‘LGBT’, 8 for ‘Mental Illness’, and 7 for ‘Veterans’. Strong correlations were found between ‘Justice Involved’ and ‘Incarcerated’ (r=0.645), and between ‘Disabilities’ and ‘Chronic Pain’ (r=0.603). DISCUSSION/SIGNIFICANCE OF FINDINGS: There were more TA requests at targeted and intensive levels than basic levels suggesting the need for services to enhance readiness and build capacity. The moderate/strong correlations indicate that UHRP types were likely to coexist with other types. Future research can explore combining UHRP types that have moderate/strong correlations.
Background: The CDC has performed surveillance for invasive Staphylococcus aureus (iSA) infections through the Emerging Infections Program (EIP) since 2004. SCCmec and spa typing for clonal complex (CC) assignment and genomic markers have been used to characterize isolates. In 2019, whole-genome sequencing (WGS) of isolates began, allowing for high-resolution assessment of genomic diversity. Here, we evaluate the reliability of SCCmec typing, spa typing, and CC assignment using WGS data compared to traditional methods to ensure that backwards compatibility is maintained. Methods:S. aureus isolates were obtained from a convenience sample of iSA cases reported through the EIP surveillance system. Overall, 78 iSA isolates with diverse spa repeat patterns, CCs, SCCmec types, and antimicrobial susceptibility profiles were sequenced (MiSeq, Illumina). Real-time PCR and Sanger sequencing were used as the SCCmec and spa typing reference methods, respectively. spa-MLST mapping (Ridom SpaServer) served as the reference method for CC assignment. WGS assembly and multilocus sequence typing (MLST) were performed using the CDC QuAISAR-H pipeline. WGS-based MLST CCs were assigned using eBURST and SCCmec types using SCCmecFinder. spa types were assigned from WGS assemblies using BioNumerics. For isolate subtyping, previously published and validated canonical single-nucleotide polymorphisms (canSNPs) as well as the presence of the Panton-Valentine leukocidin (PVL) toxin and arginine catabolic mobile element (ACME) virulence factor were assessed for all genome assemblies. Results: All isolates were assigned WGS-based spa types, which were 100% concordant (78 of 78) with Sanger-based spa typing. SCCmecFinder assigned 91% of isolates (71 of 78) SCCmec types, which were 100% concordant with reference method results. Also, 7 isolates had multiple cassettes predicted or an incomplete SCCmec region assembly. Using WGS data, 96% (75 of 78) of isolates were assigned CCs; 3 isolates had unknown sequence types that were single-locus variants of established sequence types. Overall, 70 isolates had CCs assigned by the reference method; 100% (70 of 70) concordance was observed with WGS-based CCs. Analysis of canSNPs placed 42% (33 of 78) of isolates into CC8, with 17 (52%) of these isolates classified as USA300. PVL and ACME were not accurate markers for inferring the USA300 subtype as 24% (4 of 17) of isolates did not contain these markers. Conclusions:S. aureus CCs, SCCmec, and spa types can be reliably determined using WGS. Incorporation of canSNP analysis represents a more efficient method for CC8 assignment than the use of genomic markers alone. WGS allows for the replacement of multiple typing methods for increased laboratory efficiency, while maintaining backward compatibility with historical typing nomenclature.
Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.
A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.
Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).
Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
OBJECTIVES/SPECIFIC AIMS: Aim 1—estimate prevalence and associated characteristics of nonfatal, non-self-inflicted strangulation among women ages 18 and older who presented to a US emergency department between 2006 and 2013. Aim 2—explore care-seeking behaviors, the context of the care seeking, treatment expectations and perceived diagnosis in a sample of women ages 18 and older who present to a US emergency department and report being strangled by an intimate partner. Aim 3—merge and synthesize findings from both the quantitative and qualitative strands to provide a more complete understanding of post-strangulation emergency care of women. METHODS/STUDY POPULATION: This mixed-methods study will use a convergent parallel design, with a single phase of concurrent and independent data collection. Analysis of quantitative and qualitative data will be performed separately then compared, with main findings integrated during the interpretation phase and presented in a merged data analysis display. IRB review and approval will be obtained before initiating this study. Aim 1 will include a cross-sectional analysis of 2006–2013 Nationwide Emergency Department Sample (NEDS) data, from the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project (HCUP). NEDS is the US’s largest all-payer emergency department (ED) database, providing national estimates of hospital-based ED visits from ~120 to 135 million ED visits/year (weighted). For this study, we will examine data from patients meeting inclusion criteria with an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM; Medicode, 1996) code of strangulation. For this strand, females aged 18 years or older who presented to a US emergency department between 2006 and 2013 will be included. The outcome variable will be non-fatal, non-self-inflicted strangulation, defined using at least one of the ICD-9-CM codes for strangulation. These codes are: 994.7 (“asphyxiation and strangulation”), E963 (“assault by hanging and strangulation”), E983.8 (“strangulation or suffocation by other specified means undetermined whether accidentally or purposely inflicted”), and E983.9 (“strangulation or suffocation by unspecified means undetermined whether accidentally or purposely inflicted”). Patients with a concurrent ICD-9-CM code for suicide attempt (E953, “Suicide and self-inflicted injury by hanging, strangulation and suffocation”) will be excluded, to minimize self-inflicted assault events. Aim 2 will employ a narrative descriptive approach, with semistructured individual interviews to gather more information about women’s experiences when engaging the health care system after being strangled. Medical records related to the strangulation event will also be reviewed for diagnostic codes and other nursing and/or medical notes that may relate to diagnoses, treatment and referrals. For this strand, women aged 18 years or older who present for care to an urban, academic ED will be recruited, purposely sampling those reporting strangulation as a reason for their visit. We anticipate interviewing ~20–30 women to achieve saturation of information. RESULTS/ANTICIPATED RESULTS: Data from the NEDS from 2006 to 2013 will be analyzed for prevalence and associated characteristics of women seeking care after being strangled. Individual interviews and medical record reviews of a small sample of adult women will be conducted to explore women’s in-depth experiences within the health care system. Results from both the quantitative and qualitative analyses will then be collectively compared and interpreted to better synthesize the evidence from this work. Convergent and divergent findings will be presented in a merged data analysis display (Creswell and Plano Clark, 2011). Qualitative data will be used to fill the knowledge gap remaining from the quantitative analysis, and to explain and contextualize some of the findings. Such integration will help expand the current limited evidence on care of strangled women, and will identify additional research questions that will guide future research in this area. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, this study will be the first to explore this issue using a nationally representative sample of adult women who sought emergency medical care for strangulation analyzed in conjunction with a detailed qualitative analysis of strangled women’s experiences with the health care system. The resulting knowledge will be critical to informing clinical assessment, intervention and prevention efforts for this vulnerable population, as well as public policy and future research regarding this specific violence tactic.
It is unclear whether cryoablation or radiofrequency ablation offers better value for treating atrioventricular nodal re-entrant tachycardia in children. We aimed to compare the value of these procedures for treating atrioventricular nodal re-entrant tachycardia in children, with value being outcomes relative to costs.
We performed a retrospective cohort study of all atrioventricular nodal re-entrant tachycardia ablations for children (age⩽18 years) from July, 2009 to June, 2011 at our institution. Costs included fixed costs, miscellaneous hospital costs, and labour costs, and key outcomes were acute and long-term success (6 months) of the ablations. We conducted T-tests and regression analyses to investigate the associations between the ablation procedure type and the cost and success of the ablations.
Of 96 unique cases performed by three paediatric electrophysiologists, 48 were cryoablation only, 42 radiofrequency ablation only, and six were a combination. Acute success was 100% for the cryoablation only and radiofrequency ablation only cases and 83% for the combination cases. There were no notable adverse events. The average total cost was $9636 for cryoablation cases, $9708 for radiofrequency ablation cases, and $10,967 for combination cases (p=0.51 for cryoablation only versus radiofrequency ablation only). The long-term success rate was 79.1% for cryoablation only, 92.8% for radiofrequency ablation only, and 66.7% for the combination (p=0.01 for cryoablation only versus radiofrequency ablation only), but long-term success varied notably by provider.
Cryoablation and radiofrequency ablation offer similar value in the short term for the treatment of atrioventricular nodal re-entrant tachycardia in children. Differences in long-term success may vary substantially by physician, and thus may lead to differences in long-term value.
Consulting relationships between medical school faculty and the biopharmaceutical and medical device industries offer the potential to advance research and promote the translation of academic discoveries into technologies that can benefit the health of individuals and populations. Such relationships are common, and studies suggest that faculty with industry relationships are more productive than their peers without such relationships. These benefits notwithstanding, numerous academic studies, government hearings, and litigation have called attention to the potential risks associated with these relationships.
Consulting includes a broad range of activities in which a faculty member provides advice or services to a company related to his/her area of professional expertise, typically in exchange for payment. Many universities permit faculty members to devote a portion of their faculty time to consulting (e.g., one business day per week), and faculty members are typically paid directly by the company, rather than through the university.
Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.
The spectral dependence of natural light transmittance on ice algae concentration and snow depth in Arctic sea ice provides the potential to study the changing bottom-ice ecosystem using optical relationships. In this paper, we consider the use of functional data analysis techniques to describe such relationships. Specifically, we created a functional regression model describing spectral optical depth as a function of chlorophyll a concentration, snow depth and ice thickness. Measurements of the aforementioned covariates and surface and transmitted spectral irradiance were collected on landfast first-year sea ice in the High Arctic near Resolute Passage, Canada, during the spring of 2011 and used as model input. The derived model explains 75–84.5% of the variation in the observed spectral optical depth curves. No prior assumptions of snow/sea-ice optical properties are required in the application of this technique, as the model estimates the attenuation coefficients of each covariate using only the measurements mentioned above. The quality and simplicity of the model highlight the potential of functional data analysis to study the Arctic marine ecosystem.
Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case–control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.
Stormwater catch basins form part of artificial drainage systems in urban areas and can provide larval habitat for mosquito vector species of West Nile virus (WNv), such as Culex pipiens Linnaeus (Diptera: Culicidae). We evaluated the impact of management techniques and targeted applications of larvicide on larval populations of this potential WNv mosquito vector species in catch basins from the Lower Mainland of Vancouver and on Vancouver Island of British Columbia, Canada. A mixed effects logistic regression model described the relationship between larval presence and larvicide treatment while controlling for other parameters. Parameter estimates showed that larvicide treatment reduced the odds of larvae presence by a factor of ∼7.23. The model also revealed relationships between larval presence and water temperature and adjacent land use but larvicide treatment consistently reduced the presence of larvae regardless of these other factors. This knowledge can now be used to prioritise and target control efforts to most efficiently reduce WNv mosquito vector populations, and most effectively reduce the risk of WNv transmission to humans. A similar research strategy could be applied to emerging threats from other potential mosquito vectors of disease around the world, to help lower the incidence of mosquito-borne disease.
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.