bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software Price Modeling of Ertugliflozin
Authors: EILERMAN BRADLEY , TESTA LEONARD J. 
Published: June 2018

GlucosePATH is a clinically validated decision support system which creates drug regimens for patients with type 2 diabetes. Regimens are optimized for HbA1c, weight, side effect and benefit impact, adherence and cost using a composite score from 0 to 100. Used on a population level, GlucosePATH can model drug distribution for sets of clinical values, showing drug prescription frequency to that population. As new agents such as semaglutide become available, projected distribution of these options can be described at various prices. Among other things, this shows the maximum and optimal price for a new agent, given the cost and performance of existing agents.
A data set of 191 patients with HbA1c &gt;7 was drawn from a distribution of patients cared for by PCPs in a large health system. Total monthly cost of care was computed based on the mean retail cost from the GoodRX API. Using scores drawn from GlucosePATH, drugs were redistributed to find the lowest total cost at which the population’s score was &gt;70 of 100. Total retail cost of care averaged $475 per month per patient for the 191 patients. Redistributed medication at this price generated a mean composite score of 71.5 at a projected mean HbA1c of 6.9.
Two price points were established for ertugliflozin. The “maximal price” (MP) is the highest price at which use of the agent in the population does not exceed the control group’s retail cost of care and the composite score threshold is met. (That is, introducing the new agent does not increase cost or worsen results for the population.) The “maximal revenue” (MR) is the price at which the manufacturer maximizes their gross revenue for the agent in the population.
Price optimization for ertugliflozin showed a MP of approximately $300 (retail price: $270). At its MP, ertugliflozin would be prescribed to approximately 10% of the population with mean composite score of 76.8 and mean HbA1c 6.9. At ertugliflozin’s MR of approximately $175 per month, it would be prescribed to approximately 39% of the population and generate a mean composite score of 77.6 with a mean HbA1c of 6.9.

Disclosure
B. Eilerman: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Novo Nordisk Inc., Orexigen Therapeutics, Inc., Corcept Therapeutics, Eli Lilly and Company, Merck & Co., Inc., Janssen Pharmaceuticals, Inc.. Other Relationship; Self; PATH Decision Support Software LLC. L.J. Testa: Stock/Shareholder; Self; PATH Decision Support Software LLC.
Risk Factors for Pregnancy Hypertensive Disorders in a Cohort of Women with Pregestational Diabetes
Authors: OPPERMANN MARIA LUCIA R. , ALESSI JANINE , HIRAKATA VÂNIA N. , WIEGAND DANIELA , REICHELT ANGELA J. 
Published: June 2018

Background: Pregestational diabetes (PGD) is associated with increased incidence of pregnancy hypertensive disorders (PHD).
Aim: to describe incidence and risk factors for PHD in a retrospective cohort of PGD women.
Methods: Women were evaluated at a specialized prenatal care facility. PHD comprised preeclampsia and gestational hypertension. Gestational weight gain (GWG) was categorized as excessive/non-excessive (2009 IOM); A1C test was measured before the 28th gestational week; most women did not receive prepregnancy counseling.
Results: Of 220 women, 85 were type 1 and 135, type 2 diabetes. Main characteristics (type 1 x type 2) were: age 27.3 (5.7) x 33.5 (5.5) years, p&lt;0.001; self-declared white skin: 88.2% x 76.3%, p=0.044; primigravid: 48.2% x 15.6%, p&lt;0.001; previous PHD: 8.2% x 20.7%, p=0.023; CH: 14.1% x 29.6%, p=0.013; initial A1c test ≥7.0%: 84.3% x 64.3%, p=0.002; excessive GWG: 27.0% x 35.9%, p=0.264. PHD was diagnosed in 64 of 213 women (30%; 95% CI: 24.2-36.5%) and 52 (23.6%; 95% CI 18.4-29.7%) had CH. The Table lists adjusted RR for risk factors.
Conclusion: This PGD cohort showed an increased incidence of PHD, which supports early pregnancy preventive measures, as aspirin. Excessive GWG, a modifiable risk factor, may be prevented through focused prepregnancy and antenatal surveillance.
Table. Risk Factors for Pregnancy Hypertensive Disorders in 213 Women with Pregestational Diabetes.
Risk factorRelative risk95% CI pType 1 diabetes1.771.11-2.800.015Self-declared white skin3.711.18-11.680.025Primigravid1.230.79-1.920.365Chronic hypertension2.101.38-3.17&lt; 0.001Initial A1c test ≥7.0%0.700.46-1.070.102Excessive GWG1.821.26-2.620.001

Disclosure
M.R. Oppermann: None. J. Alessi: None. V.N. Hirakata: None. D. Wiegand: None. A.J. Reichelt: None.
Progression of Coronary Artery Calcification Is Associated with Clinically Relevant Cognitive Impairment in Type 1 Diabetes
Authors: GUO JINGCHUAN , NUNLEY KAREN , ROSANO CATERINA , ORCHARD TREVOR J. 
Published: June 2018

An increased risk of cognitive dysfunction has been identified in type 1 diabetes (T1D). The association between cardiovascular disease and dementia has been examined in the general population, but the relationship is not known in T1D. The study assessed the role of coronary artery calcification (CAC) on cognitive impairment in 148 mid-aged T1D patients from the Pittsburgh Epidemiology of Diabetes Complications Study cohort of childhood-onset T1D. Baseline CAC was measured in 1996-98 and repeated 4-8 years later (2000-06). Per extensive neuropsychological testing in 2010-13, 28% (41/148) of participants met the study definition of clinically relevant cognitive impairment (two or more of 7 select test scores ≥1.5SD worse than demographically appropriate published norms). Mean age and T1D duration at first CAC measure were 37 and 29 years, respectively. In logistic regression models with backward selection, allowing for previously established risk factors for cognitive impairment in this T1D cohort (sex, T1D duration, BMI, HbA1c, ApoE4 status, ankle-brachial index, statin use, proliferative retinopathy, distal symmetric polyneuropathy, and CAD), initial CAC volume was associated with cognitive impairment (OR: 1.08, 95% CI: 1.02-1.15). In those with an initial CAC&gt;0 (n=68), including both CAC volume and density scores in the model along with other risk factors, both CAC volume (positively OR: 1.21 (1.07-1.37)) and CAC density (inversely OR: 0.41 (0.18-0.93)) were associated with cognitive impairment. In those with repeated CAC measures (n=116), the annual progression of CAC volume (determined by Hokanson method) doubled the odds of having cognitive impairment (OR: 1.96 (1.18-3.28)).
Progression of CAC volume was independently associated with clinically relevant cognitive impairment in mid-age adults with long lasting T1D. In those with prevalent CAC, CAC density appears to protect against cognitive impairment when controlling for CAC volume.

Disclosure
J. Guo: None. K. Nunley: None. C. Rosano: None. T.J. Orchard: None.
Life-Course Glucose Trajectory and Cognitive Function in Middle Age—Evidence from the Bogalusa Heart Study
Authors: STUCHLIK PATRICK , CARMICHAEL OWEN , HARVILLE EMILY , HE HUA , ROMERO MARYELLEN , GUSTAT JEANETTE , FONSECA VIVIAN , BAZZANO LYDIA A. 
Published: June 2018

Although the adverse effects of elevated glucose on cognitive function have been well-documented, most cognitive evidence comes from older adults. In this study, we make use of repeated measurements across five decades of the Bogalusa Heart Study and latent class methodology to examine the association of glucose from childhood through early adulthood on cognitive function in middle age. From our cohort of n=1,298 adults, after adjustment for age, sex, race, BMI, diabetic status, smoking, physical activity, and depressive symptoms, we identified four trajectory classes of glucose over the life course: (1) “healthy and stable;” (2) “healthy but slightly increasing;” (3) “decreasing;” and (4) “sharply increasing” (Figure). The distributions of trajectory class membership were modeled with a relative cognitive z-score, computed from a battery of tests covering major neuropsychological domains. Mean z-scores, where higher indicates better relative cognitive function, for classes 1-4 were 1.04, 0.85, 0.19, and -6.69, respectively. Parameter estimates were positive for classes 1-3, and negative for class 4 (p&lt;0.05). The “sharply increasing” class was inversely associated with each individual cognitive test except Logical Memory II-Recognition. Our findings suggest increasing glucose trajectories may adversely affect cognition earlier in adulthood than previously thought.

Disclosure
P. Stuchlik: None. O. Carmichael: None. E. Harville: None. H. He: None. M. Romero: None. J. Gustat: None. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. L.A. Bazzano: None.
Elevated Parathyroid Hormone Is Associated with an Increased Mortality Risk in Type 2 Diabetes
Authors: MUENDLEIN AXEL , LEIHERER ANDREAS , SAELY CHRISTOPH H. , GEIGER KATHRIN , BRANDTNER EVA-MARIA , LARCHER BARBARA , MADER ARTHUR , FRAUNBERGER PETER , KLEBER MARCUS , DRESSEL ALEXANDER , MAERZ WINFRIED , DREXEL HEINZ 
Published: June 2018

Parathyroid hormone (PTH) is one of the main regulators of calcium homeostasis. PTH levels are elevated in primary hyperparathyroidism as well as with vitamin D deficiency or chronic kidney disease. The association of increased PTH levels with all-cause mortality in high-risk patients is unclear. We therefore investigated the impact of serum PTH on mortality risk in a large series of 939 patients undergoing coronary angiography for the evaluation of established or suspected coronary artery disease (CAD), including 244 patients with type 2 diabetes (T2DM). Prospectively, deaths were recorded over a mean follow-up period of 6.2 years. PTH at baseline was inversely associated with eGFR (rho=-0.228; p&lt;0.001) and 25-hydroxy-vitamin D (rho=-0.243; p&lt;0.001) and was positively associated with age (rho=0.122; p&lt;0.001) and BMI (rho=0.099, p=0.002). Prospectively, elevated PTH was not significantly associated with an increased mortality risk in the total study cohort (standardized HR 1.30 [0.96-1.76]; p=0.092). However, subgroup analysis with respect to T2DM showed a highly significant association of PTH with mortality in patients with T2DM (HR 2.32 [1.37-3.95]; p=0.002), but no association of PTH with mortality in nondiabetic subjects (HR 1.04 [0.82-1.32]; p=0.766). An interaction term T2DM x PTH was significant (p=0.006), indicating a significantly stronger influence of PTH on mortality risk in patients with diabetes than in individuals without T2DM. The impact of PTH on mortality risk in patients with T2DM remained significant after adjustment for age, gender, and BMI (HR 2.30 [1.34-3.93]; p=0.002) as well as after additional adjustment for, smoking, kidney function, baseline vitamin D and angiographically determined baseline CAD (HR 1.91 [1.07-3.40]; p=0.029). We conclude that elevated PTH levels are a strong and independent predictor of all-cause mortality in patients with T2DM.

Disclosure
A. Muendlein: None. A. Leiherer: None. C.H. Saely: None. K. Geiger: None. E. Brandtner: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. M. Kleber: None. A. Dressel: None. W. Maerz: None. H. Drexel: None.
The Relationship between Immigration Status and Cardiovascular Disease Risk Factors in United States Adults with Diabetes—A 14-Year Study
Authors: DAWSON APRILL , GARACCI EMMA , OZIEH MUKOSO N. , WALKER REBEKAH J. , EGEDE LEONARD E. 
Published: June 2018

Introduction: Chronic diseases such as heart disease, stroke, and type 2 diabetes are common health issues in the U.S. About 9.4% of the U.S. population has diabetes. Research shows there is a relationship between immigration status and prevalence of chronic disease. The aim of this study is to understand the relationship between immigration status and CVD risk factors such as LDL, blood pressure, hemoglobin A1c (HbA1C), and body mass index (BMI).
Methods: The study included seven waves of data from the National Health and Nutrition Examination Survey (NHANES) for individuals with diabetes, aged 20 and older between 2001-2014. Survey participants were categorized as foreign-born and U.S. born based on self-report responses. Outcome measures included BMI, blood pressure, LDL, and HbA1C, measured as part of the NHANES procedures. Survey general linear regression methods were used to model each outcome and results were weighted to calculate nationally representative estimates.
Results: Approximately, 5,414 individuals (representing 22,788,949 U.S. adults) were included in the study. Twenty-seven percent of the sample were foreign-born representing about 18% of the U.S. population. After controlling for demographics, NHANES waves, access to health care, and years of residence in the U.S. foreign-born individuals had significantly lower BMI (-3.05; p&lt;0.0001) and systolic blood pressure (-2.55; p=0.023). There was no significant difference in diastolic blood pressure, LDL, or HbA1C among foreign-born and U.S.-born.
Conclusions: Foreign-born individuals with diabetes have lower BMI and systolic blood pressure compared to U.S.-born individuals. Prior to adjusting for access to care, foreign-born had higher LDL suggesting the importance of improving access to care and ensuring that CVD risk factors are under control. Interventions focused on lowering LDL among foreign-born individuals will be critical in lowering their cardiovascular disease risk.

Disclosure
A. Dawson: None. E. Garacci: None. M.N. Ozieh: None. R.J. Walker: None. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..
A Real-World Evaluation of the Association between Cardiovascular Outcomes and T2D Therapy
Authors: THIEL ELLEN , MARDER WILLIAM D. , CEFALU WILLIAM T. , DARSOW TAMARA , PETERSEN MATT , LATTS LISA 
Published: June 2018

Data from placebo controlled, randomized clinical trials (RCTs) have demonstrated cardio-protective effects of certain diabetes therapy classes, including sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon receptor agonists (GLP-1RA). However, the majority of these trials made comparisons to placebo and there is limited data on head to head comparisons between specific classes.
We performed an observational cohort study using the Truven Health MarketScan® Research Databases (2013-2016) to compare the risk of cardiovascular events between patients initiating treatment with SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP-4is) and GLP-1-RAs vs. sulfonylureas (SUs) in a real-world setting. Propensity score weighting and doubly robust methods (boosting and Poisson regression) were used to control for differences in baseline characteristics. The primary study outcomes were hospitalization for congestive heart failure, acute myocardial infarction, stroke and a composite of all three. Lower extremity amputations were also examined. The relative risks of events in the 12 months before and after treatment initiation were compared to generate relative risk ratios.
Protective effects of SGLT2is compared to SUs were observed (Table). Interestingly, there was also a protective effect of DPP-4is on individual outcomes compared to SUs in contrast to DPP-4i vs. placebo in RCTs.

Disclosure
E. Thiel: None. W.D. Marder: Employee; Self; IBM. W.T. Cefalu: None. T. Darsow: None. M. Petersen: None. L. Latts: Other Relationship; Self; Medtronic, Novo Nordisk Inc., Sanofi.
Pericardial Adipose Tissue and Coronary Calcium in Type 1 Diabetes—The CACTI Study
Authors: KESHAWARZ AMENA , PYLE LAURA , ALMAN AMY C. , SASSANO CAPRICE , WESTFELDT ELIZABETH , SIPPL RACHEL M. , SNELL-BERGEON JANET K. 
Published: June 2018

Type 1 diabetes (T1D) and menopause are associated with higher risk of coronary artery calcium (CAC). Accumulation of pericardial adipose tissue (PAT), a pro-inflammatory visceral fat higher in post-menopausal women and associated with increased CAC, may be a mechanism by which T1D is associated with higher CAC risk. We examined the effect of PAT on the relationship between T1D and CAC in women over time.
PAT and CAC volume data were collected from CT heart scans over 4 study visits from 725 women enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (mean baseline age ± SD, 37 ± 9 years). We used repeated measures modeling to examine changes in square root-transformed CAC volume over time by T1D, menopausal status, and quartile of PAT volume after adjusting for age, central obesity, and study visit.
PAT levels did not differ by T1D status (33.5 vs. 33.7, p=0.8), but there was a significant interaction between PAT, menopause, and T1D (p=0.02) in relation to CAC volume (Figure 1). In T1D women, higher PAT was associated with higher CAC volume regardless of menopause status, but the effect was greater in post-menopausal women. There was no difference in CAC in nondiabetic (non-DM) women across PAT quartiles or by menopause status. CAC was higher in T1D than non-DM women regardless of menopause status and PAT quartile.
PAT has a greater effect on CAC in women with T1D than non-DM women, despite similar PAT volumes.

Disclosure
A. Keshawarz: None. L. Pyle: None. A.C. Alman: None. C. Sassano: None. E. Westfeldt: None. R.M. Sippl: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.
Derivation of an EMR-Based Dysglycemia Risk Score
Authors: BOWEN MICHAEL E. , SANDERS JOANNE , ZHANG SONG , SANTINI NOEL O. , LINGVAY ILDIKO , HALM ETHAN 
Published: June 2018

Few diabetes risk scores are derived from and designed for use in the electronic medical record (EMR). We developed an EMR-derived random blood glucose (RBG) diabetes risk score to detect dysglycemia (diabetes+prediabetes) and improve case identification. A RBG-risk score to detect prevalent dysglycemia (A1C≥5.7%) was derived from EMR data in an integrated safety-net health system. Primary care patients (age 18-64; resulted A1C in 2011-2014; ≥1 RBG 24 months prior to the A1C) were eligible. We excluded patients with diagnosed dysglycemia using ICD codes and lab results. Most recent RBG and EMR-extracted demographics, comorbidities, and diabetes risk factors on the date of the A1C were used to build logistic regression models predicting dysglycemia using backwards selection. Predictors retained in the final regression model were converted to a points-based risk score (Age 0-6; race 0-3, BMI 0-5; hypertension 0-1; RBG 0-13). We report dysglycemia risk, sensitivity, specificity, and PPV for clinically relevant cutpoints. The cohort included 11,387 patients (mean age 48, 65% female, 42% Hispanic, 36% black, mean BMI 32, 29% with hypertension), of whom 42% had dysglycemia. Screening criteria were met by 86% (ADA), 65% (USPSTF), and 40-60% of patients at clinically relevant Risk Scores (9-11). The Risk Score c-statistic was significantly better than both ADA (0.75 vs. 0.56; p&lt;0.001) and USPSTF (0.75 vs. 0.60; p&lt;0.001) guidelines. An example patient with a Risk Score of 9 would be: age 50, BMI 29, white, has hypertension and RBG 112. A score of 9 identified 61% of the sample as high risk (35%) for undiagnosed dysglycemia and yielded 80% sensitivity, 53% specificity, PPV 56%, and NPV 78%. Using a cutpoint of 9, if the Risk Score were run on 1000 patients, 610 would undergo screening, 335 new cases of dysglycemia would be detected, and 85 cases would be missed. An EMR-derived RBG-risk score capable of automation in the EMR outperforms screening guidelines to detect dysglycemia. Further validation studies are needed to determine clinical usefulness.

Disclosure
M.E. Bowen: None. J. Sanders: None. S. Zhang: None. N.O. Santini: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S. E. Halm: None.
Incidence and Risk of Celiac Disease in Individuals with Type 1 Diabetes over the Lifespan—A Population-Based Cohort Study Using the Health Improvement Network Database
Authors: VAJRAVELU MARY ELLEN , LEON DIVA DE , WEBER DAVID R. , KEREN RON , DENBURG MICHELLE R. , VERMA RITU 
Published: June 2018

Objective: Individuals with type 1 diabetes (T1D) are at increased risk for celiac disease (CD), though the incidence for those diagnosed with T1D beyond childhood is unknown. We used survival analysis to investigate the incidence and risk factors for diagnosis of CD over time in a population-based cohort of children and adults with T1D.
Methods: Retrospective cohort study using The Health Improvement Network (THIN), a primary care electronic medical records database of &gt;13 million people in the United Kingdom. Subjects were 1-35 years old at T1D diagnosis; subjects with type 2 diabetes or prevalent CD were excluded. We used Cox proportional hazards regression to identify factors associated with diagnosis of CD during follow-up. Risk factors assessed included age at T1D, sex, year of T1D diagnosis, and time-varying covariates of thyroid disease and adrenal insufficiency.
Results: Subjects (n=11,537; 43% female) had a median follow-up time of 6.8 years (IQR 2.5-14.1). CD was diagnosed in 234 (2%), with median time to diagnosis of 2.9 years (IQR 1.2-7.8); 37% were diagnosed &gt; 5 years after T1D. Incidence (per 10,000 person-years) was greater in females than males (26.9 [95% CI 22.4-31.9] vs. 16.4 [95% CI 13.4-19.9]) and in subjects &lt;10 years at T1D diagnosis (50.1 [95% CI 41.4-60.2] vs. 13.3 [95% CI 11.0-15.9]). In multivariable Cox regression, the hazard of CD was higher with younger age (HR 0.88 per year of age at T1D diagnosis, 95% CI 0.80-0.96, p=0.006), in females (HR 1.50, 95% CI 1.16-1.94, p=0.002), and with more recent year of diagnosis (HR 1.09, 95% CI 1.07-1.12, p &lt; 0.001).
Conclusions: A significant proportion of CD cases were diagnosed more than 5 years after T1D diagnosis, the time frame currently recommended for screening. A more personalized approach to CD screening, accounting for the greater risk for younger-onset and female patients with T1D, may be warranted to minimize over-testing while limiting missed diagnoses.

Disclosure
M. Vajravelu: None. D. De Leon: Employee; Spouse/Partner; Merck & Co., Inc.. Research Support; Self; Zealand Pharma A/S. Consultant; Self; XOMA Corporation, ProSciento. Research Support; Self; Biomarin Corporation. D.R. Weber: None. R. Keren: None. M.R. Denburg: Research Support; Self; Mallinckrodt Pharmaceuticals. R. Verma: None.