We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Mapping reviews (MRs) are crucial for identifying research gaps and enhancing evidence utilization. Despite their increasing use in health and social sciences, inconsistencies persist in both their conceptualization and reporting. This study aims to clarify the conceptual framework and gather reporting items from existing guidance and methodological studies. A comprehensive search was conducted across nine databases and 11 institutional websites, including documents up to January 2024. A total of 68 documents were included, addressing 24 MR terms and 55 definitions, with 39 documents discussing distinctions and overlaps among these terms. From the documents included, 28 reporting items were identified, covering all the steps of the process. Seven documents mentioned reporting on the title, four on the abstract, and 14 on the background. Ten methods-related items appeared in 56 documents, with the median number of documents supporting each item being 34 (interquartile range [IQR]: 27, 39). Four results-related items were mentioned in 18 documents (median: 14.5, IQR: 11.5, 16), and four discussion-related items appeared in 25 documents (median: 5.5, IQR: 3, 13). There was very little guidance about reporting conclusions, acknowledgments, author contributions, declarations of interest, and funding sources. This study proposes a draft 28-item reporting checklist for MRs and has identified terminologies and concepts used to describe MRs. These findings will first be used to inform a Delphi consensus process to develop reporting guidelines for MRs. Additionally, the checklist and definitions could be used to guide researchers in reporting high-quality MRs.
Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.
Aims
Examine outcome data from the first 46 individuals to complete the CCP's intervention.
Method
The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.
Results
A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.
Conclusions
The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.
Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.
Participants and Methods:
Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.
Results:
Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.
Conclusions:
Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.
The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.
Participants and Methods:
64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.
Results:
Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.
Conclusions:
LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.
In Taiwan, people with hip osteoarthritis (OA) receive a total hip arthroplasty (THA). They can apply for National Health Insurance (NHI) coverage for metal-on-polyethylene (MoP) implant or USD1,313.2 co-pay for new bearing surface materials. This study aimed to report the number of first primary THAs, and calculate the costs of THA by different choices of prothesis implant.
Methods
A retrospective cohort study of patients aged 50 years or older who had OA (as an indication for THA) from 1 January 2010 through to 31 December 2018 was established from Taiwan’s NHI Claims Data. The cohort was followed-up until 31 December 2019. THA Implant combinations were defined by bearing surface materials e.g., “ceramic-metal” into alumina or composites made from alumina and zirconia, including metal-on-polyethylene (MOP), ceramic-metal composite ceramic-on-polyethylene (c-COP), alumina ceramic-on-ceramic (a-COC), ceramic-metal composite ceramic-on-ceramic (c-COC). Since only MOP was covered by the NHI, patients who chose the COP or COC implant had to pay for additional costs. We used hospital costs comparison data to calculate the average out-of-pocket (OOP) costs for different implant combinations.
Results
This study comprised 23,560 patients with first primary THA over 9 years. The number of patients of first primary THA increased from 1,802 in 2010 to 3,251 in 2018. The mean age of patients at baseline was 68 years, and the majority were women (70.6%). The share of users for each THA implant type were: MOP implant (49.2%), c-COC implant, (20.8%), a-COC implant, (6.5%), and c-COP implant, 5.9%. The average OOP costs of each implant were: USD3,578.60 for c-COC (SD=381.80), USD2,073.00 for a-COC (SD=279.80), and USD2,082.1 for c-COP (SD=334.1).
Conclusions
Although only MOP was fully covered by NHI, only about 50% of the OA patients chose this type of implant, and 26.7 percent chose alumina and zirconia ceramic composite despite this being a much higher OOP cost. Whether choosing more expensive implants would be cost-effective for THA in Taiwan’s healthcare system requires further analysis.
In this chapter, we argue that a distinct concept of “aesthetic hope” emerges from the way Kierkegaard’s Aesthete treats hope [Haab] and its relationship to recollection [Erindring] in “The Unhappiest One” and “Rotation of Crops.” We first show that aesthetic hope is distinct from the two other kinds of hope discussed by Kierkegaard: temporal hope and eternal hope. We then consider the suggestion that aesthetic hope is also an expression of despair – an inverse hope against hope, which seeks to avoid disappointment by hoping for things that are in some sense certain. The aesthete’s recommendation that we hope in such a way illuminates Kierkegaard’s view of the “dialectic” of temporal hope and eternal hope. Finally, we explore the treatment of hope in Either/Or as essentially involving a controlled, attentional element that anticipates some contemporary trends in the philosophy of hope.
Previous literature attempted to gain insight into financial abuse involving people with dementia by analysing court cases, but these studies were limited in sample size or scope. This study collected 214 court rulings directly related to the financial decisions of people with dementia to identify characteristics of the financial abuse victim, perpetrators and the types of assets. The models of bystander intervention and routine activity theory were used as conceptual models to guide analysis regarding the role of bank staff as well as the court's decision in cases of financial abuse. The majority of financial abuse perpetrators were family members (73.8%), as opposed to outsiders (19.2%). Transfer of real estate was the most common legal issue, and land was the most common financial asset involved. Difficult intra-family relationships seem to pose a great risk of financial abuse involving people with dementia since adult children were found to be the most likely perpetrators (52.7%) but also plaintiffs accusing financial abuse (57.6%). In accordance with the bystander intervention model, bank staff were more likely to be suspicious of financial abuse when an outsider was regarded as the perpetrator. In accordance with the routine activity theory model, the court was more likely to acknowledge the case as an invalid financial decision when an outsider was regarded as the perpetrator in financial abuse cases. Since people with dementia suffer from greater losses due to their family members, future policies should establish guidelines for front-line bank staff to identify warning signs to reduce the risk of financial abuse involving people with dementia, not only to prevent fraud by outsiders but also exploitation by family members.
Recent arguments claim that behavioral science has focused – to its detriment – on the individual over the system when construing behavioral interventions. In this commentary, we argue that tackling economic inequality using both framings in tandem is invaluable. By studying individuals who have overcome inequality, “positive deviants,” and the system limitations they navigate, we offer potentially greater policy solutions.
Buffelgrass [Pennisetum ciliare (L.) Link] is an invasive C4 perennial bunchgrass that is a threat to biodiversity in aridlands in the Americas and Australia. Topography influences P. ciliare occurrence at large spatial scales, but further investigation into the relationship between local-scale topography and P. ciliare growth and reproduction would be beneficial. Further, density-dependent effects on P. ciliare growth and reproduction have been demonstrated in greenhouse experiments, but the extent to which density dependence influences P. ciliare in natural populations warrants further investigation. Here we present a study on the relationships between local-scale topography (aspect and slope gradient) and vegetation characteristics (shrub cover, P. ciliare cover, and P. ciliare density) and their interactions on individual P. ciliare plant size and reproduction. We measured slope gradient, aspect, shrub cover, P. ciliare cover, P. ciliare density, and the total number of live culms and reproductive culms of 10 P. ciliare plants in 33 4 by 4 m plots located in 11 transects at the Desert Laboratory at Tumamoc Hill, Tucson, AZ, USA. We modeled the relationships at the local scale of (1) P. ciliare cover and density with aspect and slope gradient and (2) P. ciliare size and reproduction with abiotic (slope gradient and aspect) and biotic (P. ciliare cover and density and native shrub and cacti cover) characteristics. Aspect and slope gradient were poor predictors of P. ciliare cover and density in already invaded sites at the scale of our plots. However, aspect had a significant relationship with P. ciliare plant size and reproduction. Pennisetum ciliare plants on south-facing aspects were larger and produced more reproductive culms than plants on other aspects. Further, we found no relationship between P. ciliare density and P. ciliare plant size and reproduction. Shrub cover was positively correlated with P. ciliare reproduction. South-facing aspects are likely most vulnerable to fast spread and infilling by new P. ciliare introductions.
We describe a large outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) involving an acute-care hospital emergency department during December 2020 and January 2021, in which 27 healthcare personnel worked while infectious, resulting in multiple opportunities for SARS-CoV-2 transmission to patients and other healthcare personnel. We provide recommendations for improving infection prevention and control.
To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass.
Methods:
We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0–18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria.
Results:
We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common.
Conclusion:
There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.
To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.
Design, setting, and participants:
Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.
Methods:
Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.
Results:
In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.
Conclusions:
Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.
Background: Blood cultures are fundamental in the diagnosis and treatment of sepsis. Culture practices vary widely, and overuse can lead to false-positive results and unnecessary antibiotics. Our objective was to describe the implementation of a multisite quality improvement collaborative to reduce unnecessary blood cultures in pediatric intensive care unit (PICU) patients, and its 18-month impact on blood culture rates and safety metrics. Methods: In 2018, 14 PICUs joined the Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children (Bright STAR) Collaborative, designed to understand and improve blood culture practices in critically ill children. Guided by a centralized multidisciplinary study team, sites first reviewed existing evidence for safe reduction of unnecessary blood cultures and assessed local practices and barriers to change. Subsequently, local champions developed and implemented clinical decision-support tools informed by local patient needs to guide new blood-culture practices. The coordinating study team facilitated regular evaluations and discussions of project progress through monthly phone calls, site visits if requested by sites or the study team, and collaborative-wide teleconferences. The study team collected monthly blood culture rates and monitored for possible delays in obtaining blood cultures using a standardized review process as a safety balancing metric. We compared 24 months of baseline data to 18 months of postimplementation using a Poisson regression model accounting for the site-specific patient days and correlation of culture use within a site over time. Results: Across the 14 sites, before implementation, 41,768 blood cultures were collected over 259,701 PICU patient days. The mean preimplementation site-specific blood culture rate was 15.7 cultures per 100 patient days (rate range, 9.6–48.2 cultures per 100 patient days). After implementation, 22,397 blood cultures were collected over 208,171 PICU patient days. The mean postimplementation rate was 10.4 cultures per 100 patient days (rate range, 4.7–28.3 cultures per 100 patient days), which was 33.6% lower than the preimplementation (relative rate 0.66; 95% CI, 0.65–0.68 p <0.01). In 18 months post-implementation, sites reviewed 793 positive blood cultures, and identified only one suspected delay in culture collection possibly attributable to the site’s blood culture reduction program. Conclusions: Multidisciplinary quality improvement teams safely facilitated a 33.6% average reduction in blood culture use in critically ill children at 14 hospitals. Future collaborative work will determine the impact of blood culture diagnostic stewardship on antibiotic use and other important patient safety outcomes.
ABSTRACT IMPACT: Extrapolating from mouse data we explored eosinophil content in human adipose tissue and its effect on adipocyte biology potentially leading to the discovery of novel therapeutic targets for treatment of obesity and insulin resistance. OBJECTIVES/GOALS: The interaction between immune cells and adipose tissue (AT) in obesity has not been fully elicited. Mouse models of diet-induced-obesity show AT resident eosinophils (EOS) help preserve insulin sensitivity (IS). As data in human obesity are lacking, here we explored AT-EOS content and their role in AT metabolism in subjects with and without obesity. METHODS/STUDY POPULATION: We recruited lean (L) subjects and patients with obesity (Ob) to undergo abdominal subcutaneous AT biopsy and evaluation of insulin resistance (IR) by determination of HOMA-IR. Circulating EOS were isolated from all participants under fasting conditions and exposed to high glucose (HG) or high lipids (HL) for 4 hrs. AT EOS number was assessed via FACS analysis. Circulating EOS and AT mRNA was assessed by qPCR for multiple genes involved in inflammation and cell migration. To evaluate the effect of EOS on primary human adipocytes, in vitro cultures were exposed for 4 days to either interleukin-4 (IL-4), interleukin-13 (IL-13) or to human EOS. Adipocytes mRNA levels were evaluated for genes involved in adipogenesis and lipid metabolism. RESULTS/ANTICIPATED RESULTS: 16 lean, IS subjects (BMI 22.5+ 0.4kg/m2) and 22 age-matched IR patients with obesity (BMI: 38.9 + 1.0kg/m2) participated. We observed a ratio of 2:1 in AT EOS content of L vs Ob subjects (P<0.03). To assess the reduced AT-EOS content in obesity, we evaluated expression of Chemokine-C receptor 3 (CCR3) in circulating EOS. We show decreased CCR3 mRNA levels in Ob vs L subjects (P=0.006). We expect HL in vitro experiments on peripheral EOS of L subjects to affect CCR3 mRNA levels. In AT of Ob subjects, we found a significant decreased expression of Eotaxin 2, the main EOS chemokine binding CCR3 expressed on EOS. Preliminary data from in vitro primary adipocytes culture suggest for IL-4 and IL-13 to increase mRNA level of Peroxisome Proliferator Activated Receptor Gamma (PPARG), the master regulator of adipogenesis. DISCUSSION/SIGNIFICANCE OF FINDINGS: Comparable to animal studies, we found a decrease of AT-EOS content in patients with obesity. Alterations in CCR3/Eotaxin 2 signaling may be involved. IL-4 &IL-13 are secreted predominantly by EOS and appear to directly regulate gene expression in human adipocytes. These data represent the first evidence for a novel role of EOS in human AT biology.
On coronavirus disease 2019 (COVID-19) wards, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid was frequently detected on high-touch surfaces, floors, and socks inside patient rooms. Contamination of floors and shoes was common outside patient rooms on the COVID-19 wards but decreased after improvements in floor cleaning and disinfection were implemented.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
The landscape of antimicrobial resistance (AMR) surveillance is changing rapidly. The primary objective of this study was to assess the benefit of linking population-based infection prevention and control surveillance data on methicillin-resistant Staphylococcus aureus (MRSA) to hospital discharge abstract data (DAD). We assessed the value of this novel data linkage for the characterization of hospital-acquired (HA) and community-acquired MRSA (CA-MRSA) cases.
Methods:
Incident inpatient MRSA surveillance data for all adults (≥18 years) from 4 acute-care facilities in Calgary, Alberta, between April 1, 2011, and March 31, 2017, were linked to DAD. Personal health number (PHN) and gender were used to identify specific individuals, and specimen collection time-points were used to identify specific hospitalization records. A third common variable on admission date between these databases was used to validate the linkage process. Descriptive statistics were used to characterize HA-MRSA and CA-MRSA cases identified through the linkage process.
Results:
A total of 2,430 surveillance records (94.6%) were successfully linked to the correct hospitalization period. By linking surveillance and administrative data, we were able to identify key differences between patients with HA- and CA-MRSA. These differences are consistent with previously reported findings in the literature. Data linkage to DAD may be a novel tool to enhance and augment the details of base surveillance data.
Conclusion and recommendations:
This is the first Canadian study linking a frontline healthcare-associated infection AMR surveillance database to an administrative population database. This work represents an important methodological step toward complementing traditional AMR surveillance data practices. Data linkage to other data types, such as primary care, emergency, social, and biological data, may be the basis of achieving more precise data focused around AMR.
A new protocol has been devised for determining elastic properties of natural biocomposites in the form of bivalve shells under wet and dry conditions. Four-point bending on shell slices of Mytilus edulis, Ensis siliqua, and Pecten maximus give generally lower and more reliable values of Young’s modulus, E, than those in the literature from three-point bending, due to the more even distribution of strain. Finite element analysis of the prismatic microstructure of Pinna nobilis, obtained by X-ray tomography, shows that values of E ≈ 20 GPa can be understood in terms of the real microstructure containing a small proportion of organic matrix phase with E ≈ 1 GPa and a dominant proportion of calcite with E ≈ 90 GPa. Higher values of E obtained by nanoindentation give results which are biased toward the properties of the carbonate phase rather than of the biocomposite as a whole.
OBJECTIVES/SPECIFIC AIMS: The primary aim is to assess differences in therapeutic effect between MSC and EPC EVs on acute ischemic rat hearts through delivery in a biocompatible and shear-thinning hydrogel. Primary outcomes for therapeutic assessment include an in-vitro angiogenesis assay and in-vivo hemodynamic analysis, mainly identifying differences in ejection fraction and contractility. Secondary hemodynamic outcomes include cardiac output, stroke volume, and end-diastolic pressure volume relationship (EDPVR). Secondary structural outcomes include post-mortem scar analysis and immunohistochemistry (IHC) staining for angiomyogenesis. METHODS/STUDY POPULATION: MSCs and EPCs will be cultured according to previously published protocols. EVs will be isolated from cultured cell lines through precipitation methods with polyethylene glycol. EVs will be qualitatively analyzed with nanoparticle tracking analysis (NTA) and flow cytometry. The shear thinning hydrogel (STG) will be constructed using a hyaluronic backbone conjugated to adamantane or beta-cyclodextrin, ultimately facilitating guest-host interactions with shear thinning properties. Controls and treatment groups mixed with the hydrogel will be injected into the border zone of infarcted Wistar rat hearts immediately following a left anterior descending artery ligation. Hemodynamic assessment will be performed at four weeks through left ventricular catheter based pressure-volume recordings. Ex-vivo analysis will include scar thickness assessment using Masson collagen staining and IHC stain for vessel (anti-vonWillebrand factor; anti-Isolectin) and myocyte formation (anti-cardiac Troponin I). RESULTS/ANTICIPATED RESULTS: We hypothesize that, in-vitro, MSC-EVs will demonstrate non-inferior angiogenic potential as compared to EPC-EVs. We posit that MSC-EVs will demonstrate superior therapeutic effect to EPC-EVs in-vivo as measured by functional hemodynamics and structural assessment. We have successfully isolated MSC and EPC EVs and have validated uniformity across EV populations (Figure 1). Preliminary data from the angiogenesis assay (n=3) demonstrated that MSC-EV and EPC-EV produce non-significantly different angiogenic potential as measured by number of vascular meshing extremes (p=0.144) and length of master vascular segment (p=0.193), with significant differences compared to either positive or negative controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Novel regenerative therapies are needed for patients with a history of AMI given current limitations to therapy and sequelae of ischemic heart disease. Delivery of extracellular vesicles through a shear-thinning gel is a novel “off-the-shelf” translational approach to address the current clinical need.