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.
The growing utility and availability of genome-scale sequencing has led to increasingly broad incorporation across specialty disciplines of clinical research. However, classification of clinical relevance of genetic variation is an inherently clinical task, and the expertise to perform the necessary analysis, confirmation and reporting of these variants is not available in all research teams; consequently, disclosure of genomic variants to research participants remains challenging for many researchers. Advancing genomic medicine as a standard of care first requires institutional commitment and partnerships in supporting genomics in varied research studies that are inclusive of return of results to participants.
Materials and methods:
The University of North Carolina at Chapel Hill has vast experience with genetics in both clinical and research realms. By utilizing historical experience and input from key players, the Clinical GENomic analYSIS (GENYSIS) core facility was created as a case study and aims to provide a roadmap for research organizations to implement their own genomic sequencing core facilities.
Results:
The core has established a molecular sign-out conference, partnered with other core facilities on campus, and provides five main services: bioinformatics, variant analysis, clinical reporting, post-test services, and consultation with project advising. This paper presents case examples with discussion of continuous methodology improvements and embedded educational activities.
Conclusion:
This novel shared research resource enables clinical researchers with limited staff and genomics expertise to provide clinically relevant results to their study participants, expanding the reach of genomics research.
Cluster environments influence galaxy evolution by curtailing star formation activity, notably through ram-pressure stripping (RPS). This process can leave observable signatures – such as gas tails and truncated gas discs – that are crucial for understanding how RPS affects galaxies. In this study, using spatially resolved spectroscopic data from the SAMI Galaxy Survey, we identify galaxies undergoing or recently affected by RPS in eight nearby clusters (${0.029\lt z\lt 0.058}$), through a visual classification scheme based on the ionised gas (H$\alpha$+[NII]$\lambda$6584) morphologies, split into ‘unperturbed’, ‘asymmetric’, and ‘truncated’. Alongside, we measure non-parametric structural parameters (concentration, asymmetry, and offset between gas and stars) to quantify the ionised gas morphologies. We find that combinations of parameters such as concentration, shape asymmetry, and stellar-ionised gas centre offsets are useful in categorising the degree of RPS in line with their ionised gas morphologies. The projected phase-space analysis shows that asymmetric galaxies are found in a narrow region in cluster-centric distance (${0.1\lt R/R_{200}\lt 0.6}$, where ${R}_{200}$ is the characteristic cluster radius) and have a larger dispersion in line-of-sight velocity ($\sigma(|v_{\text{pec}}|)_\mathrm{Asym} = 0.71^{+0.09}_{-0.07}\ \sigma_{200}$, with $\sigma_{200}$ being the cluster velocity dispersion within ${R}_{200}$), compared to the truncated and unperturbed samples that are more broadly distributed and predominantly located at larger cluster-centric distances. This suggests that asymmetric galaxies are likely recent infallers – having crossed within 0.5 $R{_{200}}$ in the past $\sim$1 Gyr. In terms of star formation, RPS candidates (asymmetric and truncated) yield a much steeper resolved star-forming main sequence (rSFMS; $\Sigma_\mathrm{SFR} - \Sigma_\ast$) relation compared to the unperturbed counterparts, primarily emerging from having lower $\Sigma_\mathrm{SFR}$ values for the low mass density regime (i.e. $\mathrm{log} \ \Sigma_\ast \lesssim 8 \ \mathrm{M}_\odot \ \mathrm{kpc^{-2}}$), with the steepest gradient deriving from the truncated sample. Moreover, radial specific star formation rate profiles introduce different trends for unperturbed and RPS candidates. Star formation in RPS candidates is suppressed in the outskirts relative to unperturbed galaxies and is more prominent for the truncated sample compared to the asymmetric counterparts. In contrast, central (i.e. ${r/r_{\text{eff}}} \lt 0.5$) star formation activity in RPS candidates is comparable with that in their unperturbed and field counterparts, suggesting no elevated activity. Taken together, this suggests an evolutionary trend linked to the RPS stage, where unperturbed galaxies likely represent recently accreted systems (pre-RPS), while asymmetric and truncated galaxies may correspond to populations undergoing RPS and post-RPS phases, respectively, favouring outside-in quenching.
This study investigated the hypothesis that a natural biopolymer system could simultaneously mitigate and detect aflatoxin M1 (AFM1) contamination in milk. AFM₁, the hydroxylated metabolite of aflatoxin B₁, is a potent carcinogen that remains stable during milk processing and continues to pose significant food safety concerns. The research therefore aimed to determine the prevalence of moulds and AFM1 in raw buffalo and cow milk from Giza Governorate, Egypt, and to evaluate the performance of a novel natural biopolymer complex composed of chitosan, β-cyclodextrin, AFM₁-specific antibodies and anthocyanins, designed for dual functionality in AFM₁ adsorption and diagnostic signal enhancement. Total mould counts were assessed following the ISO protocol, while milk composition and somatic cell count (SCC) were determined by Bentley 150 scan. AFM1 detection was initially performed by thin-layer chromatography (TLC) and subsequently quantified by a validated reversed-phase high-performance liquid chromatography (HPLC) method. The HPLC method exhibited excellent performance with linearity (R2 = 0.99999), sensitivity (LOD 0.002 µg/L, LOQ 0.007 µg/L) and precision (RSD ≤ 1.5%). The lowering in milk compositional quality was statistically significant (P < 0.05) with elevated SCC in AFM₁-positive samples. Screening revealed AFM1 contamination in 28% of buffalo and 56% of cow milk samples, with mean concentrations of 0.084 µg/L and 0.188 µg/L, respectively. Application of the natural biopolymer achieved AFM1 reductions of 65–73% in buffalo milk and 83–90% in cow milk, while anthocyanins within the polymer provided concentration-dependent diagnostic signals. Sensory evaluation indicated that treated milk maintained acceptable organoleptic properties without adverse effects on compositional quality. These findings emphasise the prospective use of natural biopolymers as dual-function analytical and mitigation tools for AFM1 in milk, offering a reliable approach for routine milk safety monitoring.
Polarimetric multi-offset radio-echo sounding offers improved constraints on englacial thermal conditions, basal properties and ice crystal orientation compared to standard monostatic observations. Nevertheless, such surveys are uncommon in glaciology and are typically limited in offset due to cable losses. In the 2023–24 austral summer, we deployed two radar systems on Eastwind Glacier and the McMurdo Ice Shelf in Antarctica, collecting five polarimetric common-midpoint (CMP) surveys. Using an Autonomous phase-sensitive Radio-Echo Sounder (ApRES), modified with off-the-shelf radio frequency-over-fiber (RFoF) hardware and a low-loss fiber optic link, we detect bed reflections at offsets up to the equivalent of four ice thicknesses, well beyond the theoretical point of total internal reflection. A second, cable-less system built around a software-defined radio (SDR) was deployed simultaneously as an unsynchronized receiver recording the same ApRES transmitter. These co-located datasets demonstrate the potential for cabled radar systems with integrated RFoF technology for extending maximum offsets by overcoming attenuation losses inherent to coaxial cables. Furthermore, we perform polarimetric amplitude-vs-offset analysis to probe glacier dielectric structure. Finally, we present data from deployment of the fiber optic system on Thwaites Glacier, where we detect bed reflections at an offset of 4 km, demonstrating operation on thick ice (~2.2 km).
As the global population ages, the prevalence of cognitive decline is rising, creating urgent demand for proactive strategies that support brain health and healthy ageing. Ergothioneine, a unique dietary amino-thione absorbed via the OCTN1 transporter, has recently gained attention for its potential as a neuroprotective, longevity-promoting compound. This review synthesizes growing evidence from observational, interventional and mechanistic studies. Observational data consistently associate low blood ergothioneine levels with cognitive impairment, neurodegenerative diseases, cardiovascular disorders, frailty and mortality. Interventional trials in older adults suggest that ergothioneine supplementation may improve cognition, memory, sleep quality and stabilize neurodegeneration biomarkers, with no safety concerns at doses up to 25 mg/day. Mechanistic studies reveal that ergothioneine acts through multiple pathways: mitigating oxidative stress, reducing neuroinflammation, preserving mitochondrial function and potentially modulating neurogenesis and NAD+ metabolism, although some mechanisms require further investigation. Beyond cognition, ergothioneine shows promise in supporting other physiological systems relevant to ageing, including cardiovascular, metabolic, gut, eye, auditory, liver, kidney, immune, skin and lung health. Together, current evidence positions ergothioneine as a promising nutritional intervention for promoting cognitive resilience and systemic health in ageing, although larger, long-term interventional trials are needed to confirm causality and optimize use.
Prior studies have shown contradicting results regarding adrenal gland volume (AGV) in depressed patients, with some reporting significant enlargement and others not.
Objectives
The aim of this study was to retrospectively compare CT image segmentations of the adrenal glands in patients with depression to a control group with stringent exclusion criteria to minimize confounding factors.
Methods
We included patients diagnosed with depression (ICD-10: F32/33) who underwent abdominal CT imaging between 2012 and 2022 and did not have any other psychiatric disorders. Diagnoses that could potentially influence AGV were excluded. The resulting 31 depressed patients were compared to a matching control group of 31 patients without depression. The AGV was manually segmented in thin-sliced reconstructions (≤1 mm).
Results
Total AGV in the depressed group was 6.78 (5.19-7.56) cm3 compared to 6.90 (5.54-10.05) cm3 in the control group. There was no significant difference in AGV between the two groups after adjusting for age, height, and weight. A positive correlation was observed between AGV and height (r=0.41, p<0.001) and weight (r=0.52, p<0.001). Males showed significantly larger AGV than females (p≤0.001), and left AGV was significantly larger than right AGV (p<0.001). Patients within the depressed group who underwent imaging after a suicide attempt showed larger total AGV compared to the control group, though not statistically significant.
Conclusions
AGV is not increased in the well-selected cohort of depressed patients in this study, which contrasts with some previous reports in literature. Further multi-centric studies are required to identify potentially influencing factors such as attempted suicide.
Parachute science is the problematic and extractive practice of non-local researchers taking data, knowledge and information from communities of which they are not members, failing to engage the local community and local scientists, marginalizing them in most aspects of the research, and using the results to their own benefit. Perpetuated by colonialism and unequal access to resources such as funding, education and data, it is harmful to local scientists and undervalues the contributions of the community as a whole. Ultimately, it erodes trust within the scientific community and, more broadly, builds dependence on foreign researchers and makes science less global and collaborative. Increasing international and cross-cultural collaborations while being careful to avoid parachute science can help minimize these impacts. Here, we offer our perspectives on parachute science and suggestions on how to avoid it, based on our experiences conducting research internationally with diverse scientists and communities, including both academics and non-academics. Instead of a parachute, we suggest opening the scientific “umbrella” to incorporate diverse perspectives and local contributions in generating relevant and impactful scientific insight.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The urgency and scale of the COVID-19 pandemic demanded a coordinated response from public health agencies and the biomedical research community. The National COVID Cohort Collaborative (N3C) was established as a centralized enclave in 2020 to support the study of COVID-19 across the U.S. The Institutional Development Award for Clinical and Translational Research (IDeA-CTR) centers enhanced N3C’s national response by bringing representation from rural and medically underserved communities. This improved the representation of our diverse populations in the N3C Enclave and its use for research by IDeA-state investigators.
Methods:
We developed an organizational structure across the IDeA-CTRs to improve research productivity in resource-challenged areas of the U.S. This socio-technical ecosystem, informed by community input, included a governance committee and two workstreams. The operations workstream focused on data management and regulatory compliance, while the navigation, education, analysis, and training (NEAT) workstream supported educational and analytical activities for the N3C Enclave.
Results:
Our collaborative approach led to participation by 12 IDeA-CTRs, representing over 400 investigators from 23 sites. The shared governance, investigator engagement, and resource pooling enhanced research productivity and engagement with researchers across IDeA states. Participation in this IDeA-CTR N3C consortium enhanced informatics research capacity and collaboration across the IDeA-CTRs for participating networks.
Conclusions:
This collaborative model provides a roadmap and framework for future efforts among IDeA-CTRs and other academic partnerships. The socio-technical ecosystem fostered collectivism and team science, enabling the consortium to achieve far more than isolated efforts could, offering valuable insights for interdisciplinary research across geographically dispersed communities.
Current clinical guidelines for people at risk of heart disease in Australia recommend nutrition intervention in conjunction with pharmacotherapy(1). However, Australians living in rural and remote regions have less access to medical nutritional therapy (MNT) provided by Accredited Practising Dietitians (APDs) than their urban counterparts(2). The aim of the HealthyRHearts study was to trial the delivery of MNT by APDs using telehealth to eligible patients of General Practitioners (GPs) located in small to large rural towns in the Hunter New England region(3) of New South Wales, Australia. The study design was a 12-month pragmatic randomised controlled trial. The key outcome was reduced total cholesterol. The study was place-based, meaning many of the research team and APDs were based rurally, to ensure the context of the GPs and patients was already known. Eligible participants were those assessed as moderate-to-high risk of CVD by their GP. People in the intervention group received five MNT consults (totalling two hours) delivered via telehealth by APDs, and also answered a personalised nutrition questionnaire to guide their priorities and to support personalised dietary behaviour change during the counselling. Both intervention and control groups received usual care from their GP and were provided access to the Australian Eating Survey (Heart version), a 242-item online food frequency questionnaire with technology-supported personalised nutrition reports that evaluated intake relative to heart healthy eating principles. Of the 192 people who consented to participate, 132 were eligible due to their moderate-to-high risk. Pre-post participant medication use with a registered indication(4) for hypercholesterolemia, hypertension and glycemic control were documented according to class and strength (defined daily dose: DDD)(5). Nine GP practices (with 91 participants recruited) were randomised to the intervention group and seven practices (41 participants) were randomised to control. Intervention participants attended 4.3 ± 1.4 out of 5 dietetic consultations offered. Of the132 people with baseline clinical chemistry, 103 also provided a 12-month sample. Mean total cholesterol at baseline was 4.97 ± 1.13 mmol/L for both groups, with 12-m reduction of 0.26 ± 0.77 for intervention and 0.28 ± 0.79 for control (p = 0.90, unadjusted value). Median (IQR) number of medications for the intervention group was 2 (1–3) at both baseline and 12 months (p = 0.78) with 2 (1–3) and 3 (2–3) for the control group respectively. Combined DDD of all medications was 2.1 (0.5–3.8) and 2.5 (0.75–4.4) at baseline and 12 months (p = 0.77) for the intervention group and 2.7 (1.5–4.0) and 3.0 (2.0–4.5) for the control group (p = 0.30). Results suggest that medications were a significant contributor to the management of total cholesterol. Further analysis is required to evaluate changes in total cholesterol attributable to medication prescription relative to the MNT counselling received by the intervention group.
Paediatric ventricular assist device patients, including those with single ventricle anatomy, are increasingly managed outside of the ICU. We used retrospective chart review of our single centre experience to quantify adverse event rates and ICU readmissions for 22 complex paediatric patients on ventricular assist device support (15 two ventricles, 7 single ventricle) after floor transfer. The median age was 1.65 years. The majority utilised the Berlin EXCOR (17, 77.3%). There were 9 ICU readmissions with median length of stay of 2 days. Adverse events were noted in 9 patients (41%), with infection being most common (1.8 events per patient year). There were no deaths. Single ventricle patients had a higher proportion of ICU readmission and adverse events. ICU readmission rates were low, and adverse event rates were comparable to published rates suggesting ventricular assist device patients can be safely managed on the floor.
Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and quetiapine extended-release (XR) in patients with TRD treated in accordance with US prescribing information (USPI).
Methods
ESCAPE-TRD (NCT04338321) was a randomized, open-label, rater-blinded phase 3b trial investigating ESK versus quetiapine XR for acute and maintenance treatment of patients with TRD. This secondary analysis included patients aged 18–64 years who were treated/dosed according to USPI. The primary endpoint was remission, defined as Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤ 10. Treatment-emergent adverse events (TEAEs) leading to discontinuation were summarized descriptively.
Results
Among 636 patients in this secondary analysis (ESK, n = 316; quetiapine XR, n = 320), significantly more ESK-treated patients achieved remission starting at week 8 (28.3% versus 18.6%; P = 0.005) through week 32 (55.7% versus 36.3%; P < 0.001), compared with quetiapine XR–treated patients. There were clinically and statistically significant improvements in MADRS scores with ESK versus quetiapine XR at each visit from day 8 onwards. Fewer patients discontinued treatment because of TEAEs with ESK (4.5%) versus quetiapine XR (10.1%).
Conclusions
Consistent with the primary analysis, this secondary analysis demonstrated that ESK improves short- and long-term outcomes compared with quetiapine XR in patients with TRD treated according to USPI.
The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.
Glauconite from the oxidized and reduced zones of soil-geologic columns at two Coastal Plain sites, one in Maryland and one in New Jersey, was examined by Mössbauer spectroscopy. The data indicate that glauconite in the reduced zones had a higher proportion of its structural iron in the ferrous, as opposed to the ferric state. The Fe2+/Fe3+ ratio ranged from 0 to 0.2 for the glauconite from the oxidized zone and was about 0.35 for the glauconite in the reduced zones. Despite the presence of pyrite in the reduced zone, which might be expected to make ferric iron unstable because of the presence of sulfide S, about 75% of the Fe in the glauconite in the reduced zone was in the ferric state. Thin section analysis showed some glauconite in the reduced zones to be intimately associated with pyrite and some aggregates of fine pyrite crystals were locally present in cracks in glauconite pellets. In the oxidized zones, pyrite was absent and the glauconite was more yellow under plane-polarized light, as opposed to more green for the glauconite in the reduced zones. These data indicate that reports of studies of glauconite should stipulate whether samples are from the oxidized or reduced zone of soil-geologic columns.
The microbiology of cardiac implantable electronic device (CIED) infections in Calgary, Alberta was described, identifying 50 infections from 2013 to 2019. The majority were Staphylococcus aureus (40.0%). There is significant economic burden, mostly related to inpatient costs, associated with CIED infections. However, there were no significant differences in costs stratified by organism.
In conflict-affected settings, prevalence of alcohol use disorders (AUDs) can be high. However, limited practical information exists on AUD management in low-income settings. Using a theory of change (ToC) approach, we aimed to identify pathways influencing the implementation and maintenance of a new transdiagnostic psychological intervention (“CHANGE”), targeting both psychological distress and AUDs in humanitarian settings. Three half-day workshops in Uganda engaged 41 stakeholders to develop a ToC map. ToC is a participatory program theory approach aiming to create a visual representation of how and why an intervention leads to specific outcomes. Additionally, five semi-structured interviews were conducted to explore experiences of stakeholders that participated in the ToC workshops. Two necessary pathways influencing the implementation and maintenance of CHANGE were identified: policy impact, and mental health service delivery. Barriers identified included policy gaps, limited recognition of social determinants and the need for integrated follow-up care. Interviewed participants valued ToC’s participatory approach and expressed concerns about its adaptability in continuously changing contexts (e.g., humanitarian settings). Our study underscores ToC’s value in delineating context-specific outcomes and identifies areas requiring further attention. It emphasizes the importance of early planning and stakeholder engagement for sustainable implementation of psychological interventions in humanitarian settings.
The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.
To establish the epidemiology of cardiac implantable electronic device (CIED) infections in Alberta, Canada, using validated administrative data.
Design:
Retrospective, population-based cohort study.
Setting:
Alberta Health Services is a province-wide health system that services all of Alberta, Canada.
Participants:
Adult patients who underwent first-time CIED implantation or generator replacement in Alberta, Canada, between January 1, 2011, and December 31, 2019.
Methods:
CIED implant patients were identified from the Paceart database. Patients who developed an infection within 1 year of the index procedure were identified through validated administrative data (International Classification of Diseases, Tenth Revision in Canada). Demographic characteristics of patients were summarized. Logistic regression models were used to analyze device type, comorbidities, and demographics associated with infection rates and mortality.
Results:
Among 27,830 CIED implants, there were 205 infections (0.74%). Having 2 or more comorbidities was associated with higher infection risk. Generator replacement procedures (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.34–0.84; P = .008), age increase of every 10 years (OR, 0.73; 95% CI, 0.66–0.82; P ≤ .001), and index procedure after 2014 were associated with decreased risk. Comparing the infected to uninfected groups, the hospitalization rates were 2.63 compared to 0.69, and the mortality rates were 10.73% compared to 3.49%, respectively (P < .001).
Conclusions:
There is a slightly lower overall rate of CIED infections Alberta, Canada compared to previously described epidemiology. Implants after 2014, and generator replacements showed a decreased burden of infection. Patients with younger age, and 2 or more comorbidities are at greatest risk of CIED infection. The burden of hospitalization and mortality is substantially higher in infected patients.
To evaluate the impact of implementing clinical decision support (CDS) tools for outpatient antibiotic prescribing in the emergency department (ED) and clinic settings.
Design:
We performed a before-and-after, quasi-experimental study that employed an interrupted time-series analysis.
Setting:
The study institution was a quaternary, academic referral center in Northern California.
Participants:
We included prescriptions for patients in the ED and 21 primary-care clinics within the same health system.
Intervention:
We implemented a CDS tool for azithromycin on March 1, 2020, and a CDS tool for fluoroquinolones (FQs; ie, ciprofloxacin, levofloxacin, and moxifloxacin) on November 1, 2020. The CDS added friction to inappropriate ordering workflows while adding health information technology (HIT) features to easily perform recommended actions. The primary outcome was the number of monthly prescriptions for each antibiotic type, by implementation period (before vs after).
Results:
Immediately after azithromycin-CDS implementation, monthly rates of azithromycin prescribing decreased significantly in both the ED (−24%; 95% CI, −37% to −10%; P < .001) and outpatient clinics (−47%; 95% CI, −56% to −37%; P < .001). In the first month after FQ-CDS implementation in the clinics, there was no significant drop in ciprofloxacin prescriptions; however, there was a significant decrease in ciprofloxacin prescriptions over time (−5% per month; 95% CI, −6% to −3%; P < .001), suggesting a delayed effect of the CDS.
Conclusion:
Implementing CDS tools was associated with an immediate decrease in azithromycin prescriptions, in both the ED and clinics. CDS may serve as a valuable adjunct to existing antimicrobial stewardship programs.
OBJECTIVES/GOALS: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endo-histologic activity and treatment-exposure in ulcerative colitis. METHODS/STUDY POPULATION: Our retrospective cohort was derived from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease. We evaluated the fungal composition of fecal samples from 98 ulcerative colitis patients across endoscopic activity (n=43), endo-histologic activity (n=41), and biologic-exposure (n=98). Across all subgroups, we assessed fungal diversity and differential abundance of specific taxonomic groups. RESULTS/ANTICIPATED RESULTS: We identified 504 unique fungal amplicon sequence variants across the cohort of 98 patients, dominated by phylum Ascomycota. Compared to endoscopic remission, patients with endoscopic activity had an increased global fungus load (p DISCUSSION/SIGNIFICANCE: Endoscopic inflammation in ulcerative colitis is associated with altered fungal diversity driven by expansion of Saccharomyces and Candida compared to remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.