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.
Objectives/Goals: To explore the caregivers’ lived experiences related to facilitators of and barriers to effective primary care or neurology follow-up for children discharged from the pediatric emergency department (PED) with headaches. Methods/Study Population: We used the descriptive phenomenology qualitative study design to ascertain caregivers’ lived experiences with making follow-up appointments after their child’s PED visit. We conducted semi-structured interviews with caregivers of children with headaches from 4 large urban PEDs over HIPAA-compliant Zoom conferencing platform. A facilitator/co-facilitator team (JH and SL) guided all interviews, and the audio of which was transcribed using the TRINT software. Conventional content analysis was performed by two coders (JH and AS) to generate new themes, and coding disputes were resolved by team members using Atlas TI (version 24). Results/Anticipated Results: We interviewed a total of 11 caregivers (9 mothers, 1 grandmother, and 1 father). Among interviewees, 45% identified as White non-Hispanic, 45% Hispanic, 9% as African-American, and 37% were publicly insured. Participants described similar experiences in obtaining follow-up care that included long waits to obtain neurology appointments. Participants also described opportunities to overcome wait times that included offering alternative healthcare provider types as well as telehealth options. Last, participants described desired action while awaiting neurology appointments such as obtaining testing and setting treatment plans. Discussion/Significance of Impact: Caregivers perceived time to appointment as too long and identified practical solutions to ease frustrations while waiting. Future research should explore sharing caregiver experiences with primary care providers, PED physicians, and neurologists while developing plans to implement caregiver-informed interventions.
To evaluate the impact of a mobile-app-based central line-associated bloodstream infection (CLABSI) prevention program in oncology clinic patients with peripherally inserted central catheters (PICCs).
Design:
Pre-post prospective cohort study with baseline (July 2015–December 2016), phase-in (January 2017–April 2017), and intervention (May 2017–November 2018). Generalized linear mixed models compared intervention with baseline frequency of localized inflammation/infection and dressing peeling. Cox proportional hazards models compared days-to-removal of lines with localized inflammation/infection. Chi-square test compared bacteremia rates before and after intervention.
Setting:
Oncology clinic at a large medical center.
Patients:
Oncology clinic adult patients with PICCs.
Intervention:
CLABSI prevention program consisting of an actionable scoring system for identifying insertion site infection/inflammation coupled with a mobile-app enabling photo-assessments and automated physician alerting for remote response.
Results:
We completed 5,343 assessments of 569 PICCs in 401 patients (baseline: 2,924 assessments, 300 PICCs, 216 patients; intervention: 2,419 assessments, 269 PICCs, 185 patients). The intervention was associated with a 92% lower likelihood of having a dressing with peeling (OR 0.08, 95%CI 0.04-0.17, P < 0.001), 53% lower local inflammation/infection (OR 0.47, 95%CI 0.27-0.84, P < 0.011), and 24% (non-significant) lower CLABSI rates (P = .63). Physician mobile-app alerting and response enabled 80% lower risk of lines remaining in place after inflammation/infection was identified (HR 0.20, 95%CI:0.14-0.30, P < 0.001) and 85% faster removal of infected lines from mean (SD) 11.1 (9.7) to 1.7 (2.4) days.
Conclusions:
A mobile-app-based CLABSI prevention program decreased frequency of inflamed/infected central line insertion sites and increased speed of removal when inflammation/infection was found.
Each day a venous catheter is retained poses unnecessary safety risks. In a retrospective evaluation of central/peripheral lines in nursing home residents receiving antibiotics, 80% were retained beyond antibiotic treatment end and nearly one third were retained longer than a week. Interventions for timely catheter removal are urgently needed.
To evaluate the impact of a mobile-app-based central line-associated bloodstream infection (CLABSI) prevention program in nursing home residents with peripherally inserted central catheters (PICCs).
Design:
Pre-post prospective cohort study with baseline (September 2015–December 2016), phase-in (January 2017–April 2017), and intervention (May 2017–December 2018). Generalized linear mixed models compared intervention with baseline frequency of localized inflammation/infection, dressing peeling, and infection-related hospitalizations. Cox proportional hazards models compared days-to-removal of lines with localized inflammation/infection.
Setting:
Six nursing homes in Orange County, California.
Patients:
Adult nursing home residents with PICCs.
Intervention:
CLABSI prevention program consisting of an actionable scoring system for identifying insertion site infection/inflammation coupled with a mobile-app enabling photo-assessments and automated physician alerting for remote response.
Results:
We completed 8,131 assessments of 817 PICCs in 719 residents (baseline: 4,865 assessments, 422 PICCs, 385 residents; intervention: 4,264 assessments, 395 PICCs, 334 residents). The intervention was associated with 57% lower odds of peeling dressings (OR 0.43, 95% CI 0.28–0.64, P < .001), 73% lower local inflammation/infection (OR = 0.27, 95% CI: 0.13–0.56, P < .001), and 41% lower risk of infection-related hospitalizations (OR = 0.59, 95% CI: 0.42–0.83, P = .002). Physician mobile-app alerting and response enabled 62% lower risk of lines remaining in place after inflammation/infection was identified (HR 0.38, CI: 0.24–0.62, P < .001) and 95% faster removal of infected lines from mean (SD) 19 (20) to 1 (2) days.
Conclusions:
A mobile-app-based CLABSI prevention program decreased the frequency of inflamed/infected central line insertion sites, improved dressing integrity, increased speed of removal when inflammation/infection were found, and reduced infection-related hospitalization risk.
The collection of repeated measures in psychological research is one of the most common data collection formats employed in survey and experimental research. The behavioral decision theory literature documents the existence of the dynamic evolution of preferences that occur over time and experience due to learning, exposure to additional information, fatigue, cognitive storage limitations, etc. We introduce a Bayesian dynamic linear methodology employing an empirical Bayes estimation framework that permits the detection and modeling of such potential changes to the underlying preference utility structure of the respondent. An illustration of revealed stated preference analysis (i.e., conjoint analysis) is given involving students’ preferences for apartments and their underlying attributes and features. We also present the results of several simulations demonstrating the ability of the proposed procedure to recover a variety of different sources of dynamics that may surface with preference elicitation over repeated sequential measurement. Finally, directions for future research are discussed.
Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours lacking a standardised timeline for treatment initiation post-diagnosis. Delays beyond 60 days are linked to poorer outcomes and higher recurrence risk.
Methods:
A retrospective review was conducted on patients over 18 with HNSCC treated with (chemo)radiation at a rural tertiary care centre (September 2020–2022). Data on patient demographics, oncologic characteristics, treatment details and delay causes were analysed using SPSS.
Results:
Out of 93 patients, 35.5% experienced treatment initiation delays (TTIs) over 60 days. Median TTI was 73 days for delayed cases, compared to 41.5 days otherwise. No significant differences in demographics or cancer characteristics were observed between groups. The primary reasons for the delay were care coordination (69.7%) and patient factors (18.2%). AJCC cancer stage showed a trend towards longer delays in advanced stages.
Conclusion:
One-third of patients faced delayed TTI, primarily due to care coordination and lack of social support. These findings highlight the need for improved multidisciplinary communication and patient support mechanisms, suggesting potential areas for quality improvement in HNSCC treatment management.
Suicide prevention strategies have shifted in many countries, from a national approach to one that is regionally tailored and responsive to local community needs. Previous Australian studies support this approach. However, most studies have focused on suicide deaths which may not fully capture a complete understanding of prevention needs, and few have focused on the priority population of youth. This was the first nationwide study to examine regional variability of self-harm prevalence and related factors in Australian young people.
Methods
A random sample of Australian adolescents (12–17-year-olds) were recruited as part of the Young Minds Matter (YMM) survey. Participants completed self-report questions on self-harm (i.e., non-suicidal self-harm and suicide attempts) in the previous 12 months. Using mixed effects regressions, an area-level model was built with YMM and Census data to produce out-of-sample small area predictions for self-harm prevalence. Spatial unit of analysis was Statistical Area Level 1 (average population 400 people), and all prevalence estimates were updated to 2019.
Results
Across Australia, there was large variability in youth self-harm prevalence estimates. Northern Territory, Western Australia, and South Australia had the highest estimated state prevalence. Psychological distress and depression were factors which best predicted self-harm at an individual level. At an area-level, the strongest predictor was a high percentage of single unemployed parents, while being in an area where ≥30% of parents were born overseas was associated with reduced odds of self-harm.
Conclusions
This study identified characteristics of regions with lower and higher youth self-harm risk. These findings should assist governments and communities with developing and implementing regionally appropriate youth suicide prevention interventions and initiatives.
Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.
Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19.
Objective:
To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED.
Material and methods:
Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25).
Results:
Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data.
Conclusion:
Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.
Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD)(1). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m 2 SD 3.9) participated in a crossover, randomised, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry # ACTRN12620000437965). Participants consumed a HFHE breakfast meal (65g total fat; 33g saturated fat) together with a 250 mL dose of either intervention (Queen Garnet Plum providing 201 mg anthocyanins) or control (apricot) juice. A wash-out period of 14 days occurred between meal challenges, with a 4-day run-in period for juice consumption before each challenge. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular function, assessed using flow mediated dilatation (FMD), and microvascular cutaneous vascular reactivity, measured using Laser Speckle Contrast Imaging (LSCI), were evaluated at baseline and 2 h after the HFHE meal. Participants had a higher 2 h postprandial FMD (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor α, interleukin-1 β, or maximum microvascular perfusion following iontophoresis of acetylcholine. Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat ‘Western’ meal.
Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE.
Method:
The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers.
Results:
ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001).
Conclusions:
This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.
Burial diagenetic reactions of di- and trioctahedral clay minerals were compared in Brazilian offshore, basinal sediment sequences of Cretaceous age. Originally dioctahedral smectite-rich shales of three basins—Potiguar,Ceara, and Ilha de Santana—exhibited the classical smectite-to-illite burial pattern. Trioctahedral clay-rich shales and trioctahedral clay-mineral cements in sandstones, however, showed a burial sequence of saponite to mixed-layer chlorite/saponite with progressive increase in the percentage of chlorite layers with increasing burial depth.
The change from disordered to ordered interstratifications of chlorite/saponite occurred in the temperature range 60°-70°C at a vitrinite reflectance value of about 0.65. These values are lower than those found for the ordering of illite/smectite clays. Increasing substitution of Al for Si in tetrahedral sites, followed by fixation of interlayer hydroxide sheets was found to be the major chemical change promoting transformation of saponite to chlorite via corrensite.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
We compare the predictions of two important proposals made by De Neys to findings in the anchoring effect literature. Evidence for an anchoring-and-adjustment heuristic supports his proposal that system 1 and system 2 are non-exclusive. The relationship between psychophysical noise and anchoring effects, however, challenges his proposal that epistemic uncertainty determines the involvement of system 2 corrective processes in judgment.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
Methods
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Results
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Conclusions
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
Young people are most vulnerable to suicidal behaviours but least likely to seek help. A more elaborate study of the intrinsic and extrinsic correlates of suicidal ideation and behaviours particularly amid ongoing population-level stressors and the identification of less stigmatising markers in representative youth populations is essential.
Methods
Participants (n = 2540, aged 15–25) were consecutively recruited from an ongoing large-scale household-based epidemiological youth mental health study in Hong Kong between September 2019 and 2021. Lifetime and 12-month prevalence of suicidal ideation, plan, and attempt were assessed, alongside suicide-related rumination, hopelessness and neuroticism, personal and population-level stressors, family functioning, cognitive ability, lifetime non-suicidal self-harm, 12-month major depressive disorder (MDD), and alcohol use.
Results
The 12-month prevalence of suicidal ideation, ideation-only (no plan or attempt), plan, and attempt was 20.0, 15.4, 4.6, and 1.3%, respectively. Importantly, multivariable logistic regression findings revealed that suicide-related rumination was the only factor associated with all four suicidal outcomes (all p < 0.01). Among those with suicidal ideation (two-stage approach), intrinsic factors, including suicide-related rumination, poorer cognitive ability, and 12-month MDE, were specifically associated with suicide plan, while extrinsic factors, including coronavirus disease 2019 (COVID-19) stressors, poorer family functioning, and personal life stressors, as well as non-suicidal self-harm, were specifically associated with suicide attempt.
Conclusions
Suicide-related rumination, population-level COVID-19 stressors, and poorer family functioning may be important less-stigmatising markers for youth suicidal risks. The respective roles played by not only intrinsic but also extrinsic factors in suicide plan and attempt using a two-stage approach should be considered in future preventative intervention work.
OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.