bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and Implementation of a Real-time Monitoring Platform for Optimal Sepsis Care in an Emergency Department: Observational Cohort Study
Authors: Lee Andy Hung-Yi , Aaronson Emily , Hibbert Kathryn A , Flynn Micah H , Rutkey Hayley , Mort Elizabeth , Sonis Jonathan D , Safavi Kyan C 
Published: June 2021

Background
Sepsis is the leading cause of death in US hospitals. Compliance with bundled care, specifically serial lactates, blood cultures, and antibiotics, improves outcomes but is often delayed or missed altogether in a busy practice environment.

Objective
This study aims to design, implement, and validate a novel monitoring and alerting platform that provides real-time feedback to frontline emergency department (ED) providers regarding adherence to bundled care.

Methods
This single-center, prospective, observational study was conducted in three phases: the design and technical development phase to build an initial version of the platform; the pilot phase to test and refine the platform in the clinical setting; and the postpilot rollout phase to fully implement the study intervention.

Results
During the design and technical development, study team members and stakeholders identified the criteria for patient inclusion, selected bundle measures from the Center for Medicare and Medicaid Sepsis Core Measure for alerting, and defined alert thresholds, message content, delivery mechanisms, and recipients. Additional refinements were made based on 70 provider survey results during the pilot phase, including removing alerts for vasopressor initiation and modifying text in the pages to facilitate patient identification. During the 48 days of the postpilot rollout phase, 15,770 ED encounters were tracked and 711 patient encounters were included in the active monitoring cohort. In total, 634 pages were sent at a rate of 0.98 per attending physician shift. Overall, 38.3% (272/711) patients had at least one page. The missing bundle elements that triggered alerts included: antibiotics 41.6% (136/327), repeat lactate 32.4% (106/327), blood cultures 20.8% (68/327), and initial lactate 5.2% (17/327). Of the missing Sepsis Core Measures elements for which a page was sent, 38.2% (125/327) were successfully completed on time.

Conclusions
A real-time sepsis care monitoring and alerting platform was created for the ED environment. The high proportion of patients with at least one alert suggested the significant potential for such a platform to improve care, whereas the overall number of alerts per clinician suggested a low risk of alarm fatigue. The study intervention warrants a more rigorous evaluation to ensure that the added alerts lead to better outcomes for patients with sepsis.
Biannual Differences in Interest Peaks for Web Inquiries Into Ear Pain and Ear Drops: Infodemiology Study
Authors: Brkic Faris F , Besser Gerold , Schally Martin , Schmid Elisabeth M , Parzefall Thomas , Riss Dominik , Liu David T 
Published: June 2021

Background
The data retrieved with the online search engine, Google Trends, can summarize internet inquiries into specified search terms. This engine may be used for analyzing inquiry peaks for different medical conditions and symptoms.

Objective
The aim of this study was to analyze World Wide Web interest peaks for “ear pain,” “ear infection,” and “ear drops.”

Methods
We used Google Trends to assess the public online interest for search terms “ear pain,” “ear infection,” and “ear drops” in 5 English and non–English-speaking countries from both hemispheres based on time series data. We performed our analysis for the time frame between January 1, 2004, and December 31, 2019. First, we assessed whether our search terms were most relevant to the topics of ear pain, ear infection, and ear drops. We then tested the reliability of Google Trends time series data using the intraclass correlation coefficient. In a second step, we computed univariate time series plots to depict peaks in web-based interest. In the last step, we used the cosinor analysis to test the statistical significance of seasonal interest peaks.

Results
In the first part of the study, it was revealed that “ear infection,” “ear pain,” and “ear drops” were the most relevant search terms in the noted time frame. Next, the intraclass correlation analysis showed a moderate to excellent reliability for all 5 countries’ 3 primary search terms. The subsequent analysis revealed winter interest peaks for “ear infection” and “ear pain”. On the other hand, the World Wide Web search for “ear drops” peaked annually during the summer months. All peaks were statistically significant as revealed by the cosinor model (all P values <.001).

Conclusions
It can be concluded that individuals affected by otitis media or externa, possibly the majority, look for medical information online. Therefore, there is a need for accurate and easily accessible information on these conditions in the World Wide Web, particularly on differentiating signs and therapy options. Meeting this need may facilitate timely diagnosis, proper therapy, and eventual circumvention of potentially life-threatening complications.
1012-P: Diabetes Is Not Associated with Worse Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: ATLURI RAMTEJ , RAMIREZ MARCELO , SHAKA HAFEEZ , MURTHI MUKUNTHAN , CORPUZ CARLOS GABRIEL D. , VELAGAPUDI SUJITHA , VELAZQUEZ GENARO 
Published: June 2021

Background: Diabetes mellitus (DM) is a multisystem metabolic disorder shown to have adverse effects on lung physiology, immune responses, and antimicrobial defenses. However, the impact of DM on the development of poor in-hospital outcomes in patients with Acute COPD exacerbation (AECOPD) is unclear. We aimed to assess this very impact in our study.
Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2018. About 394,929 hospitalizations had AECOPD as a primary diagnosis and were stratified based on the presence of DM using ICD-10 codes. Multivariate regression analysis was used to adjust for confounders and analyze variables. The selection of covariates was done with a univariate screen and literature review.
Results: Out of the 394,929 hospitalized patients with AECOPD, 123,425 patients had DM. In-hospital mortality in AECOPD patients with DM was lower than those without (0.78% vs. 1.17%, p&lt;0.001). Mean length of stay (LOS) and patient costs (PC) were higher in those with DM (4.1 vs. 3.92 days and $9242 vs. $8710 respectively). When adjusted to patient demographics, comorbidities and hospital characteristics, AECOPD patients with DM had a lower risk of mortality (aOR=0.49, p&lt;0.001), myocardial infarction (MI) (aOR=0.58, p&lt;0.001), pulmonary embolism (PE) (aOR=0.71, p=0.011), and stroke (aOR=0.68, p=0.047), as well as a higher risk develop an AKI (aOR=1.07, p=0.024). COPD patients with DM had less LOS by 0.09 days (p=0.007) and PC by $236 (p=0.03) after adjusting for similar covariates. There was no statistical significance in the risk of developing respiratory failure (aOR=0.97, p=0.165) and sepsis (aOR=0.74, p=0.173).
Conclusion: DM in AECOPD did not have worse outcomes in terms of in-hospital mortality, LOS, and PC. DM patients had lower risk of MI, PE, and stroke, however, had higher risk of AKI. Further investigation is needed to understand the exact correlation between the paradoxical nature of outcomes in AECOPD in those with DM.

Disclosure
R. Atluri: None. M. Ramirez: None. H. Shaka: None. M. Murthi: None. C. D. Corpuz: None. S. Velagapudi: None. G. Velazquez: None.
1026-P: Rates and Disparities of Hypoglycemic and Hyperglycemic Emergencies and Mortality among U.S. Adults with Diabetes, 2009-2018
Authors: MCCOY ROZALINA G. , SWARNA KAVYA SINDHU , GALINDO RODOLFO J. , VAN HOUTEN HOLLY , O’CONNOR PATRICK J. , SHAH NILAY 
Published: June 2021

Severe hypoglycemia and hyperglycemia in diabetes management are dangerous yet potentially preventable. Data on contemporary trends of these events, mortality following their occurrence, and potential racial/ethnic disparities are limited. We used claims data from OptumLabs Data Warehouse to 1) examine rates of hypoglycemic and hyperglycemic emergencies among U.S. adults with diabetes between 2009 and 2018; 2) quantify 30-day and 1-year all-cause mortality after these events adjusted for age, sex, race/ethnicity, and U.S. region; and 3) assess for disparities by race/ethnicity.
Among 3,709,936 adults with diabetes (age 60.2 [SD, 13.7] years, 49.2% female, 58.5% White), the adjusted rate of hypoglycemic emergencies per 1000 person-years decreased by 41% from 2009 to 2018, from 16.2 (95% CI, 15.8-16.6) to 9.6 (9.4-9.8). The adjusted rate of hyperglycemic emergencies increased by 24%, from 4.6 (4.5-4.8) to 5.7 (5.6-5.9). Black patients had the highest risk of both events compared to Whites, with RR 1.7 (1.7-1.8) for hypoglycemic and 1.5 (1.4-1.5) for hyperglycemic emergencies. All-cause 30-day and 1-year mortality did not change over time. In 2018, 30-day adjusted mortality was 1.6% (1.4-1.8) and 1.3% (1.1-1.5) after hypoglycemic and hyperglycemic emergencies, respectively, while 1-year mortality was 10.3% (9.8-10.9) and 4.7% (4.2-5.2). The risks of 30-day and 1-year mortality after hypoglycemic emergencies were lower among Black (OR 0.85 [0.76-0.96] and OR 0.91 [0.87-0.96], respectively) and Hispanic (OR 0.81 [0.68-0.97] and OR 0.70 [0.64-0.76]) patients compared to Whites. There was no association between race/ethnicity and 30-day mortality after hyperglycemic emergencies, while the risk of 1-year mortality was lower among Hispanic patients (OR 0.73 [0.63, 0.85]) compared to Whites.
New strategies are needed to prevent hypoglycemic and hyperglycemic emergencies among people with diabetes, particularly among racial/ethnic minorities.

Disclosure
R. G. Mccoy: None. K. Swarna: None. R. J. Galindo: Consultant; Self; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi US, Valeritas, Inc., Research Support; Self; Dexcom, Inc., Novo Nordisk. H. Van houten: None. P. J. O’connor: None. N. Shah: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497)
1031-P: Wnt Regulation and Collagen Gene Expression in the Bone of Type 2 Diabetes Patients
Authors: LEANZA GIULIA , TRAMONTANA FLAVIA , CANNATA FRANCESCA , PICCOLI ALESSANDRA , FARAJ MALAK , VIOLA VIOLA , STROLLO ROCKY , NAPOLI NICOLA , POZZILLI PAOLO 
Published: June 2021

Increased circulating sclerostin levels and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Recent data from our group have shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone microarchitecture. Whether the expression of the Wnt beta-catenin target genes is altered in T2D, and whether AGEs accumulation it is associated with type 1 Collagen (COL1A1) alteration is still unknown. We hypothesized that increased SOST gene expression leads to downregulation of Wnt β- catenin target genes (TCF/LEF1) and AGEs accumulation is related to a downregulation of COL1A1 in bones from subjects with T2D. We analyzed bone tissue from femoral heads of 14 T2D postmenopausal women (mean HbA1c 6.5%) and 21 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. We found that TCF-LEF1 was significantly lower in T2D compared to non- diabetic subjects (p=0.0092). Dickkopf -1 (DKK-1), the other inhibitor of beta-catenin-dependent Wnt signalling besides sclerostin, was not different between groups (p=0.1083). However, analysis of correlation showed that DKK-1 increases with age (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) in T2D subjects. COL1A1 gene expression was lower in T2D compared to controls although significance was not fully reached (p=0.0564). Importantly, AGEs bone content was significantly higher in T2D compared to nondiabetics (1.5 fold increase; p&lt;0.0001).
In conclusion, our data show that even in patients with relatively good glycemic control, T2D affects the expression of collagen and Wnt beta-catenin target genes. We also found that accumulation of AGEs is possibly associated with alteration in collagen gene expression. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D.

Disclosure
G. Leanza: None. F. Tramontana: None. F. Cannata: None. A. Piccoli: None. M. Faraj: None. V. Viola: None. R. Strollo: None. N. Napoli: None. P. Pozzilli: None.

Funding
Campus Bio-Medico University
105-OR: An Exploratory Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Cotadutide on Energy Balance in Overweight and Obese Subjects with Type 2 Diabetes Mellitus
Authors: GOLUBIC RAJNA , KENNET JANE , PARKER VICTORIA E. , ROBERTSON DARREN , LUO DAN , HANSEN LARS , JERMUTUS LUTZ , AMBERY PHILIP , PARK ADRIAN , EVANS MARK 
Published: June 2021

Background: Cotadutide is a GLP1/glucagon receptor dual agonist under development for the treatment of nonalcoholic steatohepatitis and type 2 diabetes (T2D) with diabetic kidney disease. Early-phase clinical studies show that cotadutide achieves clinically significant weight loss. We aimed to establish mechanistically to what extent this effect is mediated via changes in energy intake (EI) or energy expenditure (EE).
Methods: We conducted a phase 2a single-center randomized double-blind placebo-controlled trial in overweight/obese adults (BMI 27-40 kg/m2) with T2D (HbA1c 6.5-8%). Participants underwent a 16-day single-blind placebo run-in and were randomized to double-blind 42-day cotadutide or placebo. Cotadutide was given subcutaneously, up to 300 µg daily. Primary outcome: % weight change from day 17 to day 59. Secondary outcomes: % and absolute changes in EI (ad libitum lunch), and EE (indirect calorimetry).
Results: A total of 19 (63%) cotadutide and 9 (78%) placebo participants completed the study. Least-squares (LS) mean weight change was -3.98% (90% CI -4.85%, -3.10%) and -1.40% (90% CI -2.66%, -0.13%) for cotadutide and placebo, respectively, p= 0.011 between groups. The cotadutide group had a striking 35% lower EI vs. placebo: LS mean -35.0% (90% CI -61.8%, -8.2%), p=0.037. Total EE (kJ/kg lean mass) after cotadutide treatment decreased vs. placebo: -6.0% vs. 0.3%, p&lt;0.001. Significant reductions in absolute resting and activity EE were noted with cotadutide after 42 days, but there was no change in resting EE (8.5%; cotadutide vs. placebo 1.2%, p=0.177) after 16 days of therapy despite a reduction in body weight. No additional safety concerns were raised.
Conclusions: Weight loss caused by cotadutide is predominantly due to reduced EI rather than increased EE. Transient preservation of EE in the early phases of cotadutide treatment may reflect glucagon receptor engagement.

Disclosure
R. Golubic: None. M. Evans: Advisory Panel; Self; Pila Pharma, Zucara Therapeutics Inc., Other Relationship; Self; Abbott Diabetes, Medtronic, Novo Nordisk, Research Support; Self; AstraZeneca, Imcyse. J. Kennet: None. V. E. Parker: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. D. Robertson: Employee; Self; AstraZeneca, Employee; Spouse/Partner; GlaxoSmithKline plc., Stock/Shareholder; Self; AstraZeneca. D. Luo: None. L. Hansen: Employee; Self; AstraZeneca. L. Jermutus: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; AstraZeneca. A. Park: Other Relationship; Self; Novo Nordisk.
1076-P: First-Fill Failure with Antihyperglycemic Medications: A Systematic Literature Review
Authors: AHMED NEHAL M. , PETERS SADIE , COOKE CATHERINE E. 
Published: June 2021

Introduction: Antihyperglycemic medications are often a necessary component of diabetes treatment to achieve adequate glycemic control and reduce the risk of complications. First fill failure (FFF) occurs when a patient does not obtain a newly prescribed medication and therefore does not take even the first dose. This phenomenon is an important clinical consideration, and the objective of this study is to summarize the evidence describing FFF with antihyperglycemic medications.
Methods: A systematic literature review using Medline (PubMed) identified articles from 2010-2019 that researched FFF to antihyperglycemic medications. To be included, studies must have reported on the prevalence, associated factors, or patient-reported reasons. Studies that solely evaluated non-adult populations, employed weaker study designs (i.e., case reports/series), performed interventions, were conducted outside of the USA, or were not written in English were excluded.
Results: The search identified 2,289 unique articles from which 11 studies were included. Estimates of the prevalence of FFF to new antihyperglycemic medications (n=8 studies) ranged from 9-21% of patients, and 1-54% of prescriptions. Results varied due to differences in study populations, data sources and whether “new prescription” was defined as no prior history of the specific medication or the medication class. Associated with FFF (n=2 studies) were higher out-of-pocket costs for the antihyperglycemic medication, non-English speaking, and non-white race/ethnicity. Patient-reported reasons for FFF (n=2 studies) included not believing the medication was needed or planning to improve health behaviors, financial burden, and concern for side effects.
Conclusion: Up to one-fifth of patients are unsuccessful in initiating a newly prescribed antihyperglycemic medication. Addressing the reasons behind FFF may improve medication initiation and contribute to better health and outcomes of those with diabetes.

Disclosure
N. M. Ahmed: None. S. Peters: None. C. E. Cooke: None.
1077-P: Alcohol Consumption, Smoking Habits, and the Risk of Incident Glomerular Hyperfiltration in Subjects with Impaired Fasting Glucose
Authors: SHIBATA MIKIKO , SATO KYOKO K. , UEHARA SHINICHIRO , NISHIDA NORIMITSU , OKAMURA KAORI , SHIBATA IZUMI , KOH HIDEO , OUE KEIKO , MORIMOTO MICHIO , HAYASHI TOMOSHIGE 
Published: June 2021

Although glomerular hyperfiltration (GHF) is a major risk of diabetic nephropathy and it is important to prevent GHF in subjects with prediabetes, it is not known which factors are associated with the risk of GHF. We prospectively examined the relationship of alcohol consumption and smoking habits to the risk of GHF in subjects with impaired fasting glucose (IFG). Study population was 2811 middle-aged Japanese men who had IFG, no proteinuria, no GHF, and no low estimated glomerular filtration rate (eGFR) at baseline, and who did not have low eGFR before the onset of GHF during the follow-up period. GHF was defined as eGFR ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the all study population of our cohort. Low eGFR was defined as eGFR &lt;60 mL/min/1.73 m2. Based on daily alcohol consumption, subjects were classified as follows: non-drinkers, 0.1-23.0, 23.1-46.0, and ≥46.1 g ethanol/day. As for smoking habits, subjects were divided into non-smokers, past smokers, and current smokers. During the 6-year follow-up period, 103 men developed GHF. After adjusted for BMI, fasting plasma glucose, systolic blood pressure, use of anti-hypertensive medications, and regular physical exercise, both daily alcohol consumption and smoking habits were independently associated with the risk of the incident GHF. Multiple-adjusted HRs of incident GHF for those who drank 0.1-23.0, 23.1-46.0, and ≥46.1 g ethanol/day were 0.94 (95% CI, 0.46-1.95), 1.34 (0.66-2.70), and 2.48 (1.19-5.15), respectively, compared with non-drinkers. Multiple-adjusted HRs of those for past smokers and current smokers were 0.86 (0.42-1.75), and 1.77 (1.00-3.14), respectively, compared with non-smokers.
In conclusion, high daily alcohol consumption and current smoking increased the risk of GHF in subjects with IFG.

Disclosure
M. Shibata: None. T. Hayashi: None. K. K. Sato: None. S. Uehara: None. N. Nishida: None. K. Okamura: None. I. Shibata: None. H. Koh: None. K. Oue: None. M. Morimoto: None.
1081-P: Serum Total Adiponectin Level Is Associated with Onset of Diabetes in Male Japanese: Tokushima Cohort Study
Authors: HATA AKIKO , MIYOSHI MASASHI , NAKAO TAKAYUKI , ICHIHARA TAKAKO , TAMURA AYAKO , MINAGAWA TAKAKO , KUWAMURA YUMI , FUNAKI MAKOTO 
Published: June 2021

Emerging evidence suggests that adiponectin secreted from adipocytes may have a preventive effect on the development of type 2 diabetes, attributable to an increase in insulin sensitivity and suppression of inflammation. However, when the East Asian population is considered, dysfunction of insulin secretion, besides insulin resistance and inflammation, has been assumed to play a significant role in the development of diabetes. Thus, the aim of the present study was to examine whether there is an association between a decrease in serum total adiponectin level and the incidence of diabetes in male Japanese, with consideration of insulin secretory function. We here report a prospective occupational-based cohort study, which was conducted during 2010-2019 in Japan. Briefly, 851 male workers without diabetes aged over 20 years were followed up prospectively. Diabetes was defined as either: 1) fasting plasma glucose ≥ 126 mg/dl, 2) HbA1c ≥ 6.5%, 3) medication for hyperglycemia or 4) postprandial plasma glucose ≥ 200 mg/dl during the follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) of serum total adiponectin level for the incidence of diabetes were estimated using a Cox proportional hazards model. In multivariate analysis after adjusting for age, BMI, smoking habit, alcohol intake, regular exercise, family history of diabetes, HDL-C, triglyceride, hypertension and HOMA-β, HR of developing diabetes was 8.61 [95%CI: 1.87 to 39.77, P=0.01] in the lowest quartile of serum total adiponectin, compared with the highest quartile. Furthermore, the risk of diabetes was 36% higher (P&lt;0.01) per 1 µg/ml decrement of serum total adiponectin level in the multivariate-adjusted model. These results suggest that serum total adiponectin level could be a biomarker for the onset of diabetes in male Japanese, even with consideration of the ability of fasting insulin secretion and adjustment of its impact.

Disclosure
A. Hata: None. M. Miyoshi: None. T. Nakao: None. T. Ichihara: None. A. Tamura: None. T. Minagawa: None. Y. Kuwamura: None. M. Funaki: Board Member; Self; Mechanogenic, Inc., Consultant; Self; Happy, Inc., Research Support; Self; Japan Tobacco Inc.