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Objectives/Goals: Our study team won a Public Health Answers to Speed Tractable Results (PHASTR) contract to conduct a target trial emulation to answer “Does metformin show a reduction of severe outcomes of COVID-19 or of Long COVID in the N3C Data Enclave?” We quickly delivered an answer due to productive technical and collaboration support in the N3C. Methods/Study Population: Our analytic plan was updated based on helpful feedback from the PHASTR program. We performed a trial emulation analysis using the N3C data, comparing adult new users of metformin to controls prescribed fluvoxamine, fluticasone, ivermectin, or montelukast. The composite outcome was Long COVID or Death (LC/D) within 180 days of COVID infection. We used entropy balancing to estimate the average treatment effect with a weighted log-linear model. Productivity was enhanced by reusing code workbooks and validated codesets from related N3C projects. The team of 4 (physician, informaticist, data programmer, and statistician) and key unpaid advisors spent 10 weeks developing and analyzing the data. Results/Anticipated Results: Totally, 9,660 patients were identified for analysis. After weighting, there were 248 in the metformin and control groups. In the metformin group, 4.0% developed LC/D vs. 8.5% in the control group, with an adjusted risk ratio (aRR) of 0.47 (95% CI 0.25 to 0.89). Results were consistent across subgroups and sensitivity analyses. The PHASTR contract structure helped produce high-quality results quickly by not only providing funding but also requiring a compressed timeline for a small team to focus on the study. The most time was spent on contract execution, enclave provisioning, and too many last-minute download requests. A project final report was submitted in March and a full manuscript was submitted in September. Discussion/Significance of Impact: The analysis was productive because the environment made reuse easy and supported rich collaborations among clinicians, informaticists, epidemiologists, statisticians, and data developers. Advice from PHASTR advisors (Axel) and N3C diabetes domain team members was also key to a faster completion.
Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.
Aim
To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.
Methods
A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.
Results
Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).
Conclusions
Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.
The Three Pillars (Harmonization, Replacement, and Justice) describe an ethical path forward and away from the use of nonhuman primates in harmful research and scientific use. Conducting nonhuman primate research in an ethical way that acknowledges their moral importance requires satisfying more rigorous guidelines and regulations modeled on those that apply to similarly vulnerable human subjects, especially children and incarcerated persons. This Element argues for the moral necessity of harmonizing human and nonhuman primate research ethics, regulations, and guidelines in a way that protects all primates, human and nonhuman. The authors call for the replacement of nonhuman primates in research with human-relevant methods that do not simply shift research onto other nonhuman animals, and challenge publics, governments, and scientific communities worldwide to implement justice in the selection and use of all research subjects. This title is also available as Open Access on Cambridge Core.
The population of adults with single-ventricle congenital heart disease (CHD) is growing. This study explores their lived experiences through an adult developmental psychology framework.
Methods:
Individuals aged 18 and older with single-ventricle CHD participated in Experience Group sessions and 1:1 interviews. Sessions were transcribed and analysed thematically. Themes were categorized by developmental domains and age group.
Results:
Of the 29 participants, 18 (62%) were female, 10 (35%) were emerging (18–29 years), 13 (45%) were established (30–45 years), and 6 (21%) were midlife adults (46–60 years). Emerging adults expressed reluctance to initiate romantic relationships and fear of burdening partners, while established adults reported strong relationships with partners deeply involved in caregiving. Emerging adults struggled with finding fulfilling work that meets their health needs, whereas established and midlife adults faced unemployment or early retirement due to health limits. Family dynamics shifted, with established and midlife adults educating their children to become caregivers. Physical limitations and low self-rated health were consistent across life stages, and midlife adults did not worry about traditional chronic conditions. Mental health concerns, including anxiety and depression, persisted across all life stages, but resiliency and positive affect were also evident.
Conclusion:
Adults with single-ventricle CHD experience developmental milestones differently, indicating the need for early anticipatory guidance in these domains to achieve optimal outcomes in adulthood.
The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.
Reducing rehospitalization has been a primary focus of hospitals and payors. Recurrence of Clostridioides difficile infection (CDI) is common and often results in rehospitalization. Factors that influence rehospitalization for CDI are not well understood.
Objective:
To determine the risk factors that influence rehospitalization caused by CDI.
Design:
A retrospective cohort study from January 1, 2018, to December 31, 2018, of patients aged ≥18 who tested positive for C. difficile while hospitalized.
Setting:
Academic hospital.
Methods:
The risk of rehospitalization was assessed across exposures during and after the index hospitalization using a Cox proportional hazards model. The primary outcome of this study was 60-day CDI-related rehospitalization.
Results:
There were 559 hospitalized patients with a positive CD test during the study period, and 408 patients were included for analysis. All-cause rehospitalization was 46.1% within 60 days of the index hospital discharge. Within 60 days of discharge, 68 patients developed CDI, of which 72.5% (49 of 68) were rehospitalized specifically for the management of CDI. The risk of rehospitalization in patients with CDI was higher among patients who were exposed to systemic antibiotics ([adjusted hazard ratio] aHR: 2.78; 95% CI, 1.36–5.64) and lower among patients who had post-discharge follow-up addressing C. difficile (aHR: 0.53; 95% CI, 0.28–0.98).
Conclusions:
Exposure to systemic antibiotics increased the risk of rehospitalization due to CDI, while post-discharge follow-up decreased the risk of rehospitalization due to CDI. Comprehensive transitions of care for hospitalized patients with C. difficile may reduce the risk of CDI-related rehospitalization.
Development promises change. It is fundamental to the word both in English and in Lao: an improvement towards a pre-determined goal, but it is a process that is never entirely complete. In the Lao-speaking parts of Thailand, promises of development have formed the key commitments of particular regimes: military and monarchical, neoliberal and capitalist. Each presents a future that is nationally focused, guided by a paternalistic hand, be it that of a general, monarch, or tycoon. Spirits, too, play into such regimes, ensuring that development projects will fulfil their promises and that more such projects will come.
But what happens when these goals shift towards distant centres of power? Here, I examine the magico-religious aspect of these promises. As large-scale hydropower on the Mekong, part of Chinese infrastructure projects, throws the river into chaos, new regimes of development arise. In the realm of popular religion, the link between spirits and development, too, has altered, with old powers’ promises growing stale, and new ones yet to appear.
And between these two conflicting orders of power—orders that collapse state and religious dimensions—emerge different pathways towards navigating the uncertain world: an appeal towards other sources of monarchical authority, a search for survival in a newly shifting and globalized realm, and a waiting for a future as yet unrevealed.
The 2008 global financial crisis and its aftermath provided fertile soil for criticism of and alternatives to the international liberal order, including the rise of financial nationalism. Contemporary financial nationalism is a view of the world that is nationalist in its motivation for political action, financial in its policy focus, and illiberal in its conception of political economy. At the same time, it is fundamentally shaped by its emergence from within the international liberal order, which both constrains the policy options of financial nationalists and provides opportunities for them to draw on transnational financial resources and institutions to advance nationalist causes. This article offers a conceptual analysis of contemporary financial nationalism that explores its fundamental characteristics, explains what is distinctive about it, delineates its four major policy subtypes, identifies the resources and capabilities required to successfully engage in it, and discusses the implications of doing so. It aids researchers in thinking about financial nationalism’s internal workings across different contexts, in understanding why it has lasted as long and spread as far as it has, in considering how it may evolve, and in contemplating how it can affect domestic and international political economies.
Recent measurements of inertial particles in isotropic turbulence (Hammond & Meng, J. Fluid Mech., vol. 921, 2021, A16) revealed surprising extreme clustering of particles at near-contact separations $(r)$, whereby the radial distribution function, $g(r)$, grows from $O(10)$ to $O(10^3)$ with a $(r/a)^{-6}$ scaling (where $a$ is the particle radius), and a surprising upturn of the mean inward particle-pair relative velocity (MIRV). Hydrodynamic interactions (HIs) were proposed to explain the extreme clustering, but despite predicting the correct scaling $(r/a)^{-6}$, the HI theory underpredicted $g(r)$ by at least two orders of magnitude (Bragg et al., J. Fluid Mech., vol. 933, 2022, A31). To further understand the extreme clustering phenomenon and the relevance of HI, we characterize $g(r)$ and particle-pair kinematics for Stokes numbers $0.07 \leq St \leq 3.68$ in a homogeneous isotropic turbulence chamber using three-dimensional (3-D) particle tracking resolved to near–contact. A drift–diffusion equation governing $g(r)$ is presented to investigate the kinematic mechanisms of particle pairs. Measurements in all 24 conditions show that when $r/a\lessapprox 20$, extreme clustering consistently occurs, scaling as $g(r) \sim (r/a)^{-k}$ with $4.5 \leq k \leq 7.6$, which increases with $St$. Here $g(r)$ varies with $St$, particle size, density and polydispersity in ways that HI cannot explain. The extreme clustering region features an inward drift contributed by particle-pair turbophoresis and an inward radial relative acceleration. The latter indicates an interparticle attractive force at these separations that HI also cannot explain. The MIRV turns upward when approaching the extreme clustering region, opposite to direct numerical simulation predictions. These observations further support our previous assessment that extreme clustering arises from particle–particle interactions, but HI is not the main mechanism.
Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.
Methods:
We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.
Results:
By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.
Conclusion:
This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.
Polymerase chain reaction (PCR) testing for the detection of C. difficile is a highly sensitive test. Some clinical laboratories have included a 2-step testing algorithm utilizing PCR plus toxin enzyme immunoassays (EIAs) to increase specificity.
Objective:
To determine the risk factors and outcomes of C. difficile PCR-positive/toxin-positive encounters compared to PCR-positive/toxin-negative encounters.
Design:
Retrospective study.
Setting:
A Veterans’ Affairs hospital.
Methods:
A retrospective case–control study of patient encounters with a positive C. difficile test by PCR and either a toxin EIA–positive assay (ie, cases) or toxin EIA–negative assay (ie, controls). Clinically relevant exposures and risk factors were determined to assess CDI recurrence at 30 days. Available encounter stool specimens were cultured for C. difficile and were subjected to restriction endonuclease analysis (REA) strain typing.
Results:
Among 130 C. difficile PCR-positive patient encounters, 80 (61.5%) were toxin EIA negative and 50 (38.5%) were toxin EIA positive. Encounters that were toxin positive were more frequently treated (96.0%) compared to toxin-negative encounters (71.3%; P < .01). A multivariable logistic regression model revealed that toxin-negative encounters were less likely to suffer a recurrent CDI episode within 30 days (odds ratio [OR], 0.20, 95% confidence interval [CI], 0.05–0.83). Additionally, a higher C. difficile PCR cycle threshold predicted a lower risk of CDI recurrence at 30 days. (OR, 0.82; 95% CI, 0.68–0.98). During the study period, the REA group Y strain accounted for most toxin-negative encounters (32.5%; P = .05), whereas REA group BI strain accounted for most toxin-positive encounters (24.3%; P = .02).
Conclusions:
A testing strategy of PCR plus toxin EIA helped predict recurrent CDI.
This collection makes a new, profound and far-reaching intervention into the rich yet little-explored terrain between Latin scholastic theory and vernacular literature. Written by a multidisciplinary team of leading international authors, the chapters honour and advance Alastair Minnis's field-defining scholarship. A wealth of expert essays refract the nuances of theory through the medium of authoritative Latin and vernacular medieval texts, providing fresh interpretative treatment to known canonical works while also bringing unknown materials to light.