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Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.
We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT admitted to our comprehensive stroke center between 2008 and 2018, 239/289 were new diagnoses and 204/239 were acute events with only 75/204 representing symptomatic CVTs not provoked by trauma or structural processes. Using ICD-10 codes in any position, sensitivity was 39.1% and positive predictive value was 94.2% for patients with a current or history of CVT and 84.0% and 52.5% for acute and symptomatic CVTs not provoked by trauma or structural processes.
Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status.
Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0–49%), good (50–99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status.
386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78–246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8–53.0% of the observed between-patient variance in collaterals.
Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.
Substance use disorders are highly prevalent, affecting millions of Americans directly (social, occupational, and health problems) and indirectly (billions of dollars in health care costs and lost revenues due to disability). This section briefly introduces the chemical classification and neurobehavioral properties of the most commonly misused substances.
Increased risk donors in paediatric heart transplantation have characteristics that may increase the risk of infectious disease transmission despite negative serologic testing. However, the risk of disease transmission is low, and refusing an IRD offer may increase waitlist mortality. We sought to determine the risks of declining an initial IRD organ offer.
Methods and results:
We performed a retrospective analysis of candidates waitlisted for isolated PHT using 20072017 United Network of Organ Sharing datasets. Match runs identified candidates receiving IRD offers. Competing risks analysis was used to determine mortality risk for those that declined an initial IRD offer with stratified Cox regression to estimate the survival benefit associated with accepting initial IRD offers. Overall, 238/1067 (22.3%) initial IRD offers were accepted. Candidates accepting an IRD offer were younger (7.2 versus 9.8 years, p < 0.001), more often female (50 versus 41%, p = 0.021), more often listed status 1A (75.6 versus 61.9%, p < 0.001), and less likely to require mechanical bridge to PHT (16% versus 23%, p = 0.036). At 1- and 5-year follow-up, cumulative mortality was significantly lower for candidates who accepted compared to those that declined (6% versus 13% 1-year mortality and 15% versus 25% 5-year mortality, p = 0.0033). Decline of an IRD offer was associated with an adjusted hazard ratio for mortality of 1.87 (95% CI 1.24, 2.81, p < 0.003).
IRD organ acceptance is associated with a substantial survival benefit. Increasing acceptance of IRD organs may provide a targetable opportunity to decrease waitlist mortality in PHT.
With the increasing focus on herbicide-resistant weeds and the lack of introduction of new modes of action, many producers have turned to planting annual cover crops as a method for reducing weed populations. Recent studies have suggested that perennial cover crops such as white clover could be used as living mulch. However, white clover is slow to establish and is susceptible to competition from winter weeds. Therefore, the objective of this study was to determine clover tolerance and weed control in established stands of white clover to several herbicides. Studies were conducted in the fall and winter of 2018 to 2019, and 2019 to 2020, at the J. Phil Campbell Research and Education Center in Watkinsville, GA, and the Southeast Georgia Research and Education Center in Midville, GA. POST applications of imazethapyr, bentazon, or flumetsulam at low and high rates, or in combination with 2,4-D and 2,4-DB, were applied when clover reached the 2- to 3-trifoliate stage. Six weeks after the initial POST application, a sequential application of bentazon and flumetsulam individually, and combinations of 2,4-D, 2,4-DB, and flumetsulam, were applied over designated plots. Clover biomass was similar across all treatments except where it was reduced by sequential applications of 2,4-D + 2,4-DB + flumetsulam in the 2019 to 2020 season, indicating that most treatments were safe for use on establishing living mulch clover. A single application of flumetsulam at the low rate or a single application of 2,4-D + 2,4-DB provided the greatest control of all weed species while minimizing clover injury compared with the nontreated check. These herbicide options allow for control of problematic winter weeds during clover establishment, thereby maximizing clover biomass and limiting canopy gaps that would allow summer weed emergence.
Nucleobases are nitrogenous bases composed of monomers that are a major constituent of RNA and DNA, which are an essential part of any cellular life on the Earth. The search for nucleobases in the interstellar medium remains a major challenge, however, the recent detection of nucleobases in meteorite samples and laboratory synthesis in simulated analogue experiments have confirmed their abiotic origin and a possible route for their delivery to the Earth. Nevertheless, cellular life is based on the interacting network of complex structures, and there is substantial lack of information on the possible routes by which such ordered structures may be formed in the prebiotic environment. In the current study, we present the evidence for the synthesis of complex structures due to shock processing of nucleobases. The nucleobases were subjected to the reflected shock temperature of 3500–7000 K (estimated) and pressure of about 15–34 bar for over ~2 ms timescale. Under such extreme thermodynamic conditions, the nucleobases sample experiences superheating and subsequent cooling. Electron microscopic studies of shock processed residue show that nucleobases result in spontaneous formation of complex structures when subjected to extreme conditions of shock. These results suggest that impact shock processes might have contributed to the self-assembly of biologically relevant structures and the origin of life.
Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50–80 years) were randomised to an AED (n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in samples of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD − 14·3 %; P < 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (–12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.
Antisaccade tasks can be used to index cognitive control processes, e.g. attention, behavioral inhibition, working memory, and goal maintenance in people with brain disorders. Though diagnoses of schizophrenia (SZ), schizoaffective (SAD), and bipolar I with psychosis (BDP) are typically considered to be distinct entities, previous work shows patterns of cognitive deficits differing in degree, rather than in kind, across these syndromes.
Large samples of individuals with psychotic disorders were recruited through the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) study. Anti- and pro-saccade task performances were evaluated in 189 people with SZ, 185 people with SAD, 96 people with BDP, and 279 healthy comparison participants. Logistic functions were fitted to each group's antisaccade speed-performance tradeoff patterns.
Psychosis groups had higher antisaccade error rates than the healthy group, with SZ and SAD participants committing 2 times as many errors, and BDP participants committing 1.5 times as many errors. Latencies on correctly performed antisaccade trials in SZ and SAD were longer than in healthy participants, although error trial latencies were preserved. Parameters of speed-performance tradeoff functions indicated that compared to the healthy group, SZ and SAD groups had optimal performance characterized by more errors, as well as less benefit from prolonged response latencies. Prosaccade metrics did not differ between groups.
With basic prosaccade mechanisms intact, the higher speed-performance tradeoff cost for antisaccade performance in psychosis cases indicates a deficit that is specific to the higher-order cognitive aspects of saccade generation.
Feeding difficulty is a known complication of congenital heart surgery. Despite this, there is a relative sparsity in the available data regarding risk factors, incidence, associated symptoms, and outcomes.
In this retrospective chart review, patients aged 0–18 years who underwent congenital heart surgery at a single institution between January and December, 2017 were reviewed. Patients with feeding difficulties before surgery, multiple surgeries, and potentially abnormal recurrent laryngeal nerve anatomy were excluded. Data collected included patient demographics, feeding outcomes, post-operative symptoms, flexible nasolaryngoscopy findings, and rates of readmission within a 1-year follow-up period. Multivariable regression analyses were performed to evaluate the risk of an alternative feeding plan at discharge and length of stay.
Three-hundred and twenty-six patients met the inclusion criteria for this study. Seventy-two (22.09%) were discharged with a feeding tube and 70 (97.22%) of this subgroup were younger than 12 months at the time of surgery. Variables that increased the risk of being discharged with a feeding tube included patient age, The Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery score, procedure group, aspiration, and reflux. Speech-language pathology was the most frequently utilised consulting service for patients discharged with feeding tubes (90.28%) while other services were not frequently consulted. The median length of stay was increased from 4 to 10 days for patients who required an enteral feeding tube at discharge.
Multidisciplinary management protocol and interventions should be developed and standardised to improve feeding outcomes following congenital heart surgery.
Clinical trials are a fundamental tool in evaluating the safety and efficacy of new drugs, medical devices, and health system interventions. Clinical trial visits generally involve eligibility assessment, enrollment, intervention administration, data collection, and follow-up, with many of these steps performed during face-to-face visits between participants and the investigative team. Social distancing, which emerged as one of the mainstay strategies for reducing the spread of SARS-CoV-2, has presented a challenge to the traditional model of clinical trial conduct, causing many research teams to halt all in-person contacts except for life-saving research. Nonetheless, clinical research has continued during the pandemic because study teams adapted quickly, turning to virtual visits and other similar methods to complete critical research activities. The purpose of this special communication is to document this rapid transition to virtual methodologies at Clinical and Translational Science Awards hubs and highlight important considerations for future development. Looking beyond the pandemic, we envision that a hybrid approach, which implements remote activities when feasible but also maintains in-person activities as necessary, will be adopted more widely for clinical trials. There will always be a need for in-person aspects of clinical research, but future study designs will need to incorporate remote capabilities.
Water-filled boreholes in cold ice refreeze in hours to days, and prior attempts to keep them open with antifreeze resulted in a plug of slush effectively freezing the hole even faster. Thus, antifreeze as a method to stabilize hot-water boreholes has largely been abandoned. In the hot-point drilling case, no external water is added to the hole during drilling, so earlier antifreeze injection is possible while the drill continues melting downward. Here, we use a cylindrical Stefan model to explore slush formation within the parameter space representative of hot-point drilling. We find that earlier injection timing creates an opportunity to avoid slush entirely by injecting sufficient antifreeze to dissolve the hole past the drilled radius. As in the case of hot-water drilling, the alternative is to force mixing in the hole after antifreeze injection to ensure that ice refreezes onto the borehole wall instead of within the solution as slush.
With human influences driving populations of apex predators into decline, more information is required on how factors affect species at national and global scales. However, camera-trap studies are seldom executed at a broad spatial scale. We demonstrate how uniting fine-scale studies and utilizing camera-trap data of non-target species is an effective approach for broadscale assessments through a case study of the brown hyaena Parahyaena brunnea. We collated camera-trap data from 25 protected and unprotected sites across South Africa into the largest detection/non-detection dataset collected on the brown hyaena, and investigated the influence of biological and anthropogenic factors on brown hyaena occupancy. Spatial autocorrelation had a significant effect on the data, and was corrected using a Bayesian Gibbs sampler. We show that brown hyaena occupancy is driven by specific co-occurring apex predator species and human disturbance. The relative abundance of spotted hyaenas Crocuta crocuta and people on foot had a negative effect on brown hyaena occupancy, whereas the relative abundance of leopards Panthera pardus and vehicles had a positive influence. We estimated that brown hyaenas occur across 66% of the surveyed camera-trap station sites. Occupancy varied geographically, with lower estimates in eastern and southern South Africa. Our findings suggest that brown hyaena conservation is dependent upon a multi-species approach focussed on implementing conservation policies that better facilitate coexistence between people and hyaenas. We also validate the conservation value of pooling fine-scale datasets and utilizing bycatch data to examine species trends at broad spatial scales.
The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk – Lite (GUMLi) randomised control trial (2015–2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.
There has been scant exploration of the social and emotional wellbeing (SEWB) of young Indigenous populations that identify as LGBTQA+ (Lesbian, Gay, Bisexual, Transgender, Queer/Questioning, Asexual +). Given the vulnerability of this cohort living in Western settler colonial societies, wider investigation is called for to respond to their needs, experiences and aspirations. This paper summarizes existing research on the topic highlighting the lack of scholarship on the intersection of youth, Indigeneity, LGBTQA+ and SEWB. The paper takes a holistic approach to provide a global perspective that draws on an emerging body of literature and research driven by Indigenous scholars in settler colonial societies. The paper points to the importance of understanding converging colonial influences and ongoing contemporary elements, such as racism and marginalization that impact on young Indigenous LGBTQA+ wellbeing.
Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
The need for experimental traumatic brain injury (TBI) models comes from the drive to better understand TBI pathophysiology in order to improve outcome. Models are surrogates for human pathology, they can be cellular (in vitro) or whole organism (in vivo). Although no model can entirely replace the need for human studies, the use of cell cultures and animals offer unique advantages. There is uniformity of subjects, and the same injury can be repeatedly recreated. They allow for the creation of simple or complex injuries, whilst offering the ability to investigate global or focal change(s) from minutes to days following the insult, and there are no recruitment or loss of follow-up issues. The greatest advantages are possibly the ability to perform multiple and invasive sampling of tissues, measure fatal end points and trial widest range of drug doses which is precluded in clinical studies.
There is limited knowledge of how individuals reflect on their involuntary admission.
To investigate, at one year after an involuntary admission,
(i) peoples perception of the necessity of their involuntary admission
(ii) the enduring impact on the relationship with their family, consultant psychiatrist and employment prospects
(iii) readmission rates to hospital and risk factors for readmission.
People that were admitted involuntarily over a 15 month period were re-interviewed at one year following discharge.
Sixty eight people were re-interviewed at one year and this resulted in a follow-up rate of 84%. Prior to discharge, 72% of people reported that their involuntary admission had been necessary however this reduced to 60% after one year. Over one third of people changed their views and the majority of these patients reflected negatively towards their involuntary admission.
One quarter of people continued to experience a negative impact on the relationship with a family member and their consultant psychiatrist one year after an involuntary admission, while 13% reported a positive impact. A similar proportion perceived that it had negative consequences in their employment.
Within one year, 43% of all patients involuntarily admitted in the study period were readmitted to hospital and half of these admissions were involuntary. Involuntary readmission was associated with a sealing over recovery style.
Peoples’ perception of the necessity of their involuntary admissions changes significantly over time. Involuntary admissions can have a lasting negative impact on the relationship with family members and treating consultant psychiatrist.