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There is a growing awareness that diversity, health equity, and inclusion play a significant role in improving patient outcomes and advancing knowledge. The Pediatric Heart Network launched an initiative to incorporate diversity, health equity, and inclusion into its 2021 Scholar Award Funding Opportunity Announcement. This manuscript describes the process of incorporating diversity, health equity, and inclusion into the Pediatric Heart Network Scholar Award and the lessons learned. Recommendations for future Pediatric Heart Network grant application cycles are made which could be replicated by other funding agencies.
An ideal vision model accounts for behavior and neurophysiology in both naturalistic conditions and designed lab experiments. Unlike psychological theories, artificial neural networks (ANNs) actually perform visual tasks and generate testable predictions for arbitrary inputs. These advantages enable ANNs to engage the entire spectrum of the evidence. Failures of particular models drive progress in a vibrant ANN research program of human vision.
In post-Brexit and post-devolution Britain, relationships among the four nations appear fragile. This article aims to discover where British citizens draw the symbolic boundaries that define in-group and out-group members between nations—in particular, England, Scotland, and Wales—and within England. Within England, we also examine class divides and the North–South divide. We operationalize symbolic boundaries through a set of new innovative measures administered in an online survey in 2019. Questions ascertain agreement that the various groups “share my values,” are “people I could get on with,” and are “straightforward and honest.” Results of our descriptive analysis suggest that boundaries are blurred between the British and the Welsh but sharper for the Scottish. We also find sharp but asymmetrical boundaries within England, between the working class and the middle class, and between Northerners and Southerners. Regional differences in perceptions of Southerners map closely onto those of how well Westminster looks after regional interests, which suggests that power imbalances reduce social cohesion.
The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).
Method:
The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.
Results:
For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).
Conclusions:
The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.
We have been using LAB (Buvidal) in Cardiff after its pandemic use was funded by Welsh Government.
Objectives
We wished to review the benefits of introducing LAB (Buvidal) into treatment during the pandemic.
Methods
This service development review of the first 73 patients treated with LAB (24mg/96mg rapid titration Welsh protocol) was analysed using Kaplan-Meier survival curves.
Results
43 (58%) male, 30 (41%) female. <25years=1, 38 (52%) aged 25-40, 34 (47%) 40-55. Prior to LAB 14% (10 people) using Espranor, 8% (6) Buprenorphine, 28% (20) Methadone. 50% (36) illicit opiates (mainly Heroin). We had continuous data for patients for up to 9 months of LAB. Two stopped for non-discontinuation reasons: One wanted to detox, one died of natural causes (LAB-unrelated). Both were excluded from discontinuation rate analysis. 55 people have data for over a month. Of these, 11 discontinued treatment. 80% remained on LAB for 1 month or more [95%CI 67-90%]. Kaplan-Meier plots showed similar discontinuation rates when comparing different OST programmes or none prior to LAB, and comparing by age, sex and initial illness severity (CGI severity). These rates all far exceeded data for traditional OST. CGI scores dramatically improved, even at one week. By month 2 all scores “much improved” or “very much improved”.
Conclusions
Buvidal (LAB) has 80% retention rates, regardless of underlying prescribed/illicit opioid /demographics. The commonly held belief that those on heroin are further from Recovery than those more stable on OAD may be incorrect. LAB may be a more acceptable and useful first line therapy that other OSTs
Disclosure
Dr Melichar has provided consultancy work, presentations, training and chaired panel discussions for all the companies in this area in the UK and some outside the UK. Recent work includes Althea (UK), Britannia (UK), Camurus (UK and Global), Martindale (U
The Trial Innovation Network (TIN) is a collaborative initiative within the National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Awards (CTSA) Program. To improve and innovate the conduct of clinical trials, it is exploring the uses of gamification to better engage the trial workforce and improve the efficiencies of trial activities. The gamification structures described in this article are part of a TIN website gamification toolkit, available online to the clinical trial scientific community.
Methods:
The game designers used existing electronic trial platforms to gamify the tasks required to meet trial start-up timelines to create friendly competitions. Key indicators and familiar metrics were mapped to scoreboards. Webinars were organized to share and applaud trial and game performance.
Results:
Game scores were significantly associated with an increase in achieving start-up milestones in activation, institutional review board (IRB) submission, and IRB approval times, indicating the probability of completing site activation faster by using games. Overall game enjoyment and feelings that the game did not apply too much pressure appeared to be an important moderator of performance in one trial but had little effect on performance in a second.
Conclusion:
This retrospective examination of available data from gaming experiences may be a first-of-kind use in clinical trials. There are signals that gaming may accelerate performance and increase enjoyment during the start-up phase of a trial. Isolating the effect of gamification on trial outcomes will depend on a larger sampling from future trials, using well-defined, hypothesis-driven statistical analysis plans.
Background: RSV is underrecognized in hospitalized adults. A better understanding of RSV in this population could help prioritize targeted viral-testing resources. Hospitalization and in-hospital outcomes are widely accepted as markers of clinical severity with respect to acute respiratory illness (ARI). We compared characteristics and clinical outcomes between adults hospitalized with ARI from October 2016 through May 2019. Methods: All hospitalized adults (≥ 18 years) who met a standardized case definition of ARI were prospectively enrolled across 3 respiratory seasons from 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Demographic data were collected during enrollment interviews, and electronic medical records (EMRs) were reviewed to extract comorbidity data. Throat and nasal swabs collected at enrollment were tested for ARI pathogens using real-time PCR assays at respective HAIVEN research laboratory sites. Characteristics and clinical outcomes of participants were compared using χ2 or nonparametric tests where appropriate. Multivariable logistic regression models were used to test associations between infection status, characteristics, and clinical outcomes, adjusting for age, sex, race, Charlson comorbidity index (CCI), body mass index (BMI), site, season, and days to admission. Results: In total, 10,311 adults were included, 22.3% (n = 2,300) were aged 18–49 years, 33.2% (n = 3,423) were aged 50–64 years, and 44.5% (n = 4,588) were aged ≥65 years. Moreover, 6% of adults tested positive for RSV (n = 622), 18.8% positive for influenza (n = 1,940), and 75.1% negative for both (n = 7,749). Obesity and age ≥65 years were significantly associated with RSV detection when compared with participants negative for both RSV and influenza. Patients aged 18–49 years and ≥65 years with RSV had significantly higher median CCI scores compared to patients with influenza (Fig. 1.). The proportion of adults with CHF or COPD was significantly (p-value Conclusions: Severe RSV illness may differ from severe influenza illness, and those infected with RSV may have different characteristics than those infected with influenza. Hospitalized adults with RSV infection were more likely to have underlying cardiopulmonary comorbidities and higher CCI scores as well as experience an extended length of hospital stay and need for mechanical ventilation. These data highlight the importance of retaining testing for RSV in older adults hospitalized with ARI.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
Design:
Longitudinal study
Participants:
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
Measurements:
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
Results:
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
Conclusions:
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury.
Methods:
Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score.
Results:
Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0–4) versus 0 (0–0), p = 0.02).
Discussion:
Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Design:
Pilot prospective multicenter surveillance study.
Setting:
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
Methods:
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
Results:
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Conclusions:
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province.
Methods:
Using administrative data from the Canadian Institute for Health Information’s (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015.
Results:
From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001).
Interpretation:
At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.
Delayed presentation to the emergency department influences acute stroke care and can result in worse outcomes. Despite public health messaging, many young adults consider stroke as a disease of older people. We determined the differences in ambulance utilization and delays to hospital presentation between women and men as well as younger (18–44 years) versus older (≥45 years) patients with stroke.
Methods:
We conducted a population-based retrospective study using national administrative health data from the Canadian Institute of Health Information databases and examined data between 2003 and 2016 to compare ambulance utilization and time to hospital presentation across sex and age.
Results:
Young adults account for 3.9% of 463,310 stroke/transient ischemic attack/hemorrhage admissions. They have a higher proportion of hemorrhage (37% vs. 15%) and fewer ischemic events (50% vs. 68%) compared with older patients. Younger patients are less likely to arrive by ambulance (62% vs. 66%, p < 0.001), with younger women least likely to use ambulance services (61%) and older women most likely (68%). Median stroke onset to hospital arrival times were 7 h for older patients and younger men, but 9 h in younger women. There has been no improvement among young women in ambulance utilization since 2003, whereas ambulance use increased in all other groups.
Conclusions:
Younger adults, especially younger women, are less likely to use ambulance services, take longer to get to hospital, and have not improved in utilization of emergency services for stroke over 13 years. Targeted public health messaging is required to ensure younger adults seek emergency stroke care.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
Methods:
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
Results:
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Conclusion:
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals’ unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference–determined cognitive statuses and subjective impairment. Results: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. Conclusions: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1–14)
Dementia prevalence is rising, and it will double in the next 20 years. This study sought to understand the prevalence of dementia in hospitalized patients with ischemic stroke, and its impact on outcomes.
Methods
Using the Canadian Institute of Health Information’s (CIHI) Discharge Abstract Database (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of admission was assessed based on hospital diagnostic codes. Characteristics and in-hospital outcomes were compared in patients with and without dementia using χ2 and negative binomial, as well as Poisson regression analysis.
Results
During the observed period, 313,138 people were admitted to a hospital in Canada for an ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia. People with dementia had older median age (84 vs. 76 years; p<0.0001), were more often female (59.6% vs. 48.4%; p<0.0001) and more often had Charlson-Deyo Comorbidity Index ≥2 (64.5% vs. 43.5%; p<0.0001). Patients with dementia were less likely to be discharged to a rehabilitation facility (adjusted risk ratio [RR] 3.089, 95% confidence interval [CI] 2.992-3.188, p<0.0001) or home independently (adjusted RR 0.756, 95% CI 0.737-0.776, p<0.0001).
Interpretation
Approximately 1 in 13 hospitalized ischemic stroke patients has coded dementia. Patients with ischemic stroke and concurrent dementia have higher mortality, face significantly more dependence after stroke and utilize greater healthcare resources than stroke patients without dementia. Causative conclusions are limited by the administrative data source. Early care planning and coordination could potentially optimize outcomes.