Objective:In utero exposure to maternal prepregnancy diabetes is associated with an increased risk for abnormal glycemic outcomes in children, including impaired glucose tolerance, insulin resistance, and type 2 diabetes. Our objective was to evaluate the timing of exposure to maternal dysglycemia and whether the effects persist into adulthood. Study Design:The Transgenerational Effects on Adult Morbidity (TEAM) Study followed offspring of mothers with prepregnancy insulin-dependent diabetes mellitus (IDDM), who participated in a Program Project Grant (PPG) between 1978 and 1995. These women had a detailed characterization of glycemic measures across pregnancy and comprehensive obstetric and delivery data. Offspring participated in a complete clinical exam, which included an oral glucose tolerance test (OGTT). Multiple regression methods were used to identify associations between trimester-specific maternal hemoglobin A1 (HbA1) standard deviation (HbA1SD) and maternal glucose profiles with offspring glycemic outcomes, adjusting for covariates. Results:Among 161 offspring up to 42 years of age (mean age, 32.3 years), first trimester HbA1SD was associated with increased offspring fasting plasma glucose and HbA1c ≥6.5% after adjusting for maternal age, family history of diabetes, presence of microvascular disease, and body mass index (BMI) at the last menstrual period. Both second- and third-trimester maternal HbA1SD were positively associated with offspring HbA1c and inversely associated with the acute insulin response to glucose (AIRg), defined as the rapid, first-phase release of insulin from pancreatic beta-cells within 10 minutes of the OGTT. Conclusion:Our findings add to the current literature showing that the association between trimester-specific gestational maternal glycemic status and offspring adverse glycemic outcome persists into adulthood in the offspring. Key Points:· Exposure to maternal IDDM is associated with offspring glycemic outcomes.. · Maternal glycohemoglobin, particularly in the first trimester, is associated with HbA1c and fasting glucose.. · Mid-late pregnancy hyperglycemia was associated with reduced offspring acute insulin response..

Objective:To identify patterns of gestational weight gain (pGWG) trajectories in the first 20 weeks of gestation and to determine the association of these patterns with the delivery of large-for-gestational-age (LGA) infants among women with insulin-dependent diabetes mellitus (IDDM). Study design:Analysis of data collected prospectively in a Diabetes in Pregnancy Program Project Grant 7/1978 to 6/1993. Sparse functional principal components analysis was used to identify clusters defining phenotypes of women with similar pGWG in the first 20 weeks of gestation. Generalized estimating equations (GEEs) were used to estimate the association between maternal phenotype according to pGWG and odds of LGA (> 90th percentile) at birth, adjusting for predefined covariates and confounders; age, age of diagnosis of diabetes, race, parity, chronic hypertension, nephropathy, retinopathy, body mass index (BMI), and glycohemoglobin A1. GEEs were also used to examine the association of LGA and total weight gain over the first 20 weeks of gestation. Results:A total of 349 pregnancies were included in this analysis. Three phenotypes of pGWG were identified and classified as high pGWG (highest 25% of trajectories; n = 84), moderate pGWG (middle 50% of trajectories; n = 176), and low pGWG (lowest 25% of trajectories; n = 89). Phenotype was positively associated with prepregnancy BMI (p < 0.0001) and total GWG (p < 0.0001). Women with high pGWG (adjusted odds ratio [aOR] = 3.54; 95% confidence interval [CI], 1.31-9.51) and moderate pGWG (aOR = 2.41; 95% CI, 1.09-5.35) had significantly increased odds of delivering an LGA infant, compared to women in the low pGWG. However, total weight gain over the first 20 weeks of gestation was not significantly associated with delivery of an LGA infant. Conclusions:Moderate or high pGWG during the first 20 weeks of gestation was associated with increased odds of delivering an LGA infant. Future studies should consider pGWG in early pregnancy rather than overall early GWG to strategize interventions when examining the likelihood of delivering an LGA infant.

Objectives:We and others have shown that maternal hyperglycemia during pregnancy in women with insulin-dependent diabetes mellitus (IDDM) influences fetal growth. Less is understood regarding how trimester-specific glycemic patterns, particularly glucose variability, shape offspring obesity risk across the life course and whether this is mediated by birthweight. Leveraging data from the Diabetes in Pregnancy Program Grant (PPG; 1978-1995) and the Transgenerational Effects on Adult Morbidity (TEAM Study; 2017-2023) cohort, we aimed to evaluate whether the association between maternal glycemic control and adult offspring obesity status was mediated in part through infant birthweight. Study Design:Maternal glycohemoglobinA1 levels were collected monthly during pregnancy and harmonized across laboratories using standard deviation units (HbA1SD). Functional principal component analysis characterized patterns in blood glucose level and variability. TEAM Study participants, adult offspring of PPG women, completed in-person or online assessments (via Zoom) of body anthropometrics. Linear mixed-effects models and generalized estimating equations estimated associations between maternal glycemia and adult offspring outcomes. Classical mediation methods tested whether birthweight mediated observed relationships. Results:Consistent with prior findings, third-trimester HbA1SD demonstrated the most consistent positive associations with adult offspring body mass index (BMI) outcomes, after adjustment for maternal BMI at last menstrual period, maternal education, gestational weight gain, and sex of offspring (for offspring weight only). There was no evidence that birthweight mediated the relationship between maternal glycemic patterns and adult offspring overweight and obesity; however, birthweight exhibited an independent direct effect on adult offspring BMI in fully adjusted models. Conclusion:Infant birthweight was not shown to be a mediator in the association of maternal gestational glycemic control and overweight/obesity in adult offspring of women with IDDM. Although birthweight does not appear to mediate these long-term associations, the findings underscore the importance of trimester-specific evaluation of blood glucose level and variability, motivating further investigation into transgenerational metabolic risk pathways. Key Points:· It is unlikely that birthweight mediates the association between gestational blood glucose levels and offspring adult obesity.. · Higher birthweight is an important risk factor for overweight and obesity in the adult offspring.. · Early gestation hyperglycemia may program obesity in adult offspring of IDDM women..

Objective:Limited data are available to describe the long-term implications of pre-pregnancy diabetes on offspring body composition in adulthood. The objective of this study was to examine the association between maternal glucose control and variation throughout pregnancy and long-term obesity in offspring. A second objective was to identify the critical windows of gestational exposure most related to the development of long-term obesity. Research Design and Methods:This cohort study included offspring of women with insulin-dependent diabetes (IDDM) who participated in the Diabetes in Pregnancy Program Project Grant (PPG) between 1978 and 1995 to evaluate the long-term implications of in utero glucose exposure. Offspring completed a comprehensive study visit which included measures of height and weight, and measures from dual-energy X-ray absorptiometry. The exposure was maternal glucose control as measured by glycohemoglobin A1 concentration (where HbA1 was represented as standard deviation units from the mean for the laboratory HBA1SD), and blood glucose level and variation across pregnancy, and by trimester, characterized using functional principal components (fPC). Outcomes were adult offspring BMI (kg/m2), as well as visceral and whole-body fat. Results:A total of 161 offspring completed a study visit. Mean offspring age at follow-up was 32.3 years (± 4.6), 50.3% were female and 17.4% identified as Black. After adjustment for covariates (maternal age, education, family history of diabetes, diabetes severity, and BMI at last menstrual period), third-trimester maternal HbA1SD was significantly associated with offspring adiposity measures including BMI, BMI ≥ 30 kg/m2, and visceral and whole-body fat mass and percentage. The third-trimester fPC representing variability of glucose demonstrated a consistent positive association with obesity outcomes but did not reach statistical significance in adjusted models. Conclusions:Our findings corroborate that the third trimester is a critical window of exposure associated with offspring adiposity. Specifically, higher levels of third-trimester maternal glycohemoglobin A1 is a risk factor for obesity in the adult offspring of IDDM mothers. Additionally, results suggest that glucose variability may increase the risk for obesity in the adult offspring.

Background: Existing data indicate recent increases in the prevalence of stroke and relevant risk factors as well as predicted continued increases in coming years. Our objective was to evaluate population-based data on the prevalence of stroke risk factors and related medication use by sex through 2021. Methods: Data on the prevalence of stroke risk factors and medication use were taken from our general population random-digit dial survey conducted during 6 time periods: 1995, 2000, 2005, 2011, 2016, and 2021. Due to survey sampling design, survey participants' characteristics (sex, race, age) are representative of the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) ischemic stroke study population. We examined the proportion of females vs. males who reported having hypertension (HTN), hyperlipidemia (HL), diabetes (DM), and current smoking and who reported using antihypertensive medications, lipid-lowering agents, aspirin, and anticoagulants (AC). Results: Over 6 study periods, a total of 12,336 participants completed the survey; 59% were female, and 25% were Black. Mean age of participants (in years) went up over time in both females (64 [SD 16 . 3] in 1995 to 69 [SD 16.4] in 2021) and males (61 [SD 15.7] in 1995 to 67 [SD 16.8] in 2021), p trend <0.0001 for both). Prevalence of HTN, DM, and HL increased over the 6 study periods in both females and males, and current smoking decreased (Figure 1, all p trend <0.0001). All preventive medications (anti-hypertensives, lipid-lowering, aspirin, and AC) assessed increased over time (Figure 2). In 2021, similar proportions of females vs. males had HTN, DM, DL, and were current smokers (p>0.05). Further, similar proportions of females vs. males were on antihypertensives, lipid-lowering medications, and aspirin, though more men than women were on AC (15% vs. 10%, p<0.05). Conclusions: In this population-based survey of residents of a 5-county region of southern Ohio and northern Kentucky, the reported prevalence of stroke risk factors increased over a 26-year period in both females and males, as did use of medications used to modify these risk factors. An increasing burden of cardiometabolic risk factors may increase stroke event rates in the future and points to the need for improved primordial prevention.

Importance Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG. Objective To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG. Design, Setting, and Participants This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 RYGB and 67 VSG followed prospectively for 8 years. Main Outcomes and Measures Patient-reported GIS before surgery and across 8 years of postoperative follow-up were assessed. We dichotomized postoperative symptom severity and analyzed the data using general linear mixed models. Results Adolescents undergoing either VSG or RYGB demonstrated significant increases in abdominal pain (10% vs. 17%), bloating (8% vs. 20%), and constipation (3% vs. 9%) between baseline and 8 years (p<0.05). Following RYGB, the prevalence of GERS was not statistically significantly different between baseline (12%) and 8 years (13%)(p>0.05). Following VSG, however, GERS increased from 9% preoperatively to 27% at 8 years (p<0.05). In adjusted analyses, VSG was associated with higher odds of GERS at 8 years (adjusted odds ratio 2.67 [1.57-4.55, 95%CI]). Conclusions and Relevance GERS represents a considerable concern pre- and post-MBS in adolescents, especially after VSG. Appropriate patient selection along with counseling and objective monitoring for pathologic consequences of gastroesophageal reflux after MBS are warranted. Trial Registration Clinicaltrials.gov Identifier: NCT00474318 Type of Study Prospective, multicenter, observational cohort Level of Evidence Level II

Maternal diabetes, a common pregnancy complication, has long-term implications for both mother and offspring. While the developmental origins of metabolic health from prenatal diabetes exposure are well known, cognitive consequences in offspring are still being explored. The timing of hyperglycemia during pregnancy that most affects cognitive development and whether these effects persist into adulthood remains unclear. This study aimed to determine the association between trimester-specific hyperglycemia exposure and adult cognition in the offspring of women with pregestational diabetes. The Transgenerational Effect on Adult Morbidity (TEAM) Study evaluated health outcomes in young adult offspring of mothers with pregestational diabetes who participated in a Diabetes in Pregnancy Program Project Grant (PPG) at the University of Cincinnati (1978-1995). The TEAM Study visit (March 2018 - August 2022) included a comprehensive clinical examination and cognitive assessment (Wechsler Abbreviated Scale of Intelligence - II). Linear regression estimated the association between prenatal hyperglycemia and offspring's perceptual reasoning and verbal comprehension. The mean age at follow-up was 32.1 years. Hyperglycemia during pregnancy was inversely associated with cognitive measures, controlling for confounders including maternal education and pre-pregnancy obesity. Higher glycohemoglobin in the second and third trimesters was significantly linked to lower IQ scores, matrix reasoning, and vocabulary subtest scores. Third-trimester hyperglycemia was also associated with lower block design subtest scores. In summary, hyperglycemia, particularly in the latter half of pregnancy, was associated with lower cognitive ability in adult offspring of women with pre-pregnancy pregestational diabetes.

BACKGROUND AND OBJECTIVES:Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period. METHODS:In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported. RESULTS:Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time. DISCUSSION:Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.

This study proposes a Bayesian joint model with extended random effects structure that incorporates nested repeated measures and provides simultaneous inference on treatment effects over time and drop-out patterns. The proposed model includes flexible splines to characterize the circadian variation inherent in blood pressure sequences, and we assess the effectiveness of an intervention to resolve pediatric obstructive sleep apnea. We demonstrate that the proposed model and its conventional two-stage counterpart provide similar estimates of nighttime blood pressure but estimates on the mean evolution of daytime blood pressure are discrepant. Our simulation studies tailored to the motivating data suggest reasonable estimation and coverage probabilities for both fixed and random effects. Computational challenges of model implementation are discussed.

The human body has abundant mechanisms to counteract hypoglycemia and prevent neuroglycopenia primarily involving the secretion of glucagon and adrenalin. Within several years from the onset of diabetes, people with type 1 diabetes lose their ability to mount a counterregulatory response to hypoglycemia and develop hypoglycemia unawareness, thus being at risk for deteriorating to a state of severe hypoglycemia and neuroglycopenia. Pregnant individuals with type 1 diabetes are particularly prone to experience severe hypoglycemia during the first half of pregnancy. This may be not only due to the institution of strict glycemic control and the nausea and vomiting prevalent during the early months of pregnancy, but also because the counterregulatory responses are further diminished during pregnancy. Severe hypoglycemia during early pregnancy does not appear to increase the risks of spontaneous abortion or congenital fetal malformations, but the potential long-term effects on the fetus are unknown. Recent technological advances have contributed to improved glycemic control and time in range as well as decreased risk of hypoglycemia in people with diabetes. These advances include treatment with insulin analogs, use of continuous glucose monitors, and closed-loop systems for administration of insulin. Limited studies have demonstrated that pregnant individuals with type 1 diabetes may also benefit from these modalities. While ongoing research continues to explore the adjustment of closed-loop systems for optimal use during pregnancy, more effort is needed to explore the optimal use of these modalities in pregnancy. · People with type 1 diabetes have diminished counterregulatory responses to hypoglycemia and frequently develop hypoglycemia unawareness.. · Pregnant individuals with type 1 diabetes are at increased risk for severe hypoglycemia particularly during the first half of pregnancy.. · Use of insulin analogs and newer technologies for insulin administration may lower the risk of hypoglycemia in pregnant individuals with type 1 diabetes..

The Diabetes in Pregnancy Program Project Grant (PPG) was a 15-year program focused on enhancing the care for women with insulin-dependent diabetes mellitus (IDDM) during pregnancy and improving the well-being of their offspring. Launched in July 1978 at the University of Cincinnati, the PPG pursued a multifaceted research agenda encompassing basic science, animal and placental studies, and maternal and neonatal clinical trials to understand the physiological and pathophysiological aspects of IDDM during pregnancy. A total of 402 singleton pregnancies in 259 women with IDDM were enrolled prior to 10 weeks gestation over the 15-year period. Of the 402 pregnancies, there were 295 live births, 1 stillbirth, 4 neonatal deaths, and 15 infants were born with major congenital malformations. Central to the program's methodology was the management of diabetes during pregnancy, involving intensive insulin therapy and meticulous monitoring using the cutting-edge technology of the time to achieve glycemic control. The extensive research of the PPG yielded profound insights into the effects of maternal diabetes on embryonic and fetal development and neonatal health. Through animal studies, notably using pregnant sheep, the program clarified the mechanisms of fetal hypoxia and metabolic disorders. Clinical trials underscored the significance of early glycemic control in mitigating the risks of spontaneous abortions, congenital malformations, and neonatal complications. The program also examined the influence of pregnancy on the progression of microvascular diseases, the role of maternal weight and weight gain in pregnancy outcomes, and the distinctive growth patterns of fetuses in IDDM pregnancies. Furthermore, the PPG probed the incidence and underlying mechanisms of hypoglycemia during pregnancy and the heightened risk of obstetric complications in IDDM patients. Our findings established a foundation of knowledge to aid clinicians, researchers, and health care providers in best practices and ensure a lasting impact on the care of pregnant women with pregestational diabetes. · Prepregnancy management reduces maternal, fetal, and neonatal complications in IDDM.. · Strict glycemic control improves many pregnancy outcomes in IDDM.. · Fetal glycemic exposure may have lifelong effects..

This study aimed to test the hypothesis that the development or deterioration of nephropathy and retinopathy over time is not affected by pregnancy in women with pregestational type 1 diabetes mellitus (T1DM).Prospective, observational study of nephropathy and retinopathy follow-up during pregnancy and in a subsequent period of 2 years in a group of pregnant women with T1DM (study group) that we compared with pair-matched non-pregnant women with T1DM (control group) who underwent similar intensive follow-up.The rate of renal microvascular complications was similar at entry, 17.4% (4/23) in the study group and 21.7% (5/23) in the control group. At the last visit, both groups had nephropathy rates of 17.4% (4/23) and paired p-value of 1.00. Similarly, the rate of retinal microvascular complications of any grade was similar in both groups and remained so at the last follow-up examination.Pregnancy per se does not appear to increase the risk for the development of, or the acceleration of the progression of retinopathy and nephropathy during a follow-up of at least 2 years in relatively healthy T1DM patients. This information is important for counseling young women with T1DM who are considering becoming pregnant. · Retinopathy and nephropathy are major complications of T1DM.. · Pregnancy per se does not appear to cause major microvascular complications in T1DM.. · Pregnancy per se does not appear to aggravate retinopathy in T1DM..

This study aimed to review the Cincinnati PPG's contribution to the understanding and treatment of neonatal hypocalcemia (NHC) in infants of diabetic mothers. This study is a retrospective review of the NIH-funded Program Project Grant (PPG) works related to mineral metabolism in type 1 diabetic pregnant women. The PPG investigators first described the epidemiology and the additional risk factors for NHC, namely prematurity and neonatal asphyxia, but also recognized the independent effect of maternal diabetes mellitus. They explored the link between NHC and maternal/neonatal hypomagnesemia. They finally conducted a randomized control trial of prevention of NHC by early administration of magnesium sulfate soon after birth to prevent NHC. The PPG in its various phases has allowed to reveal the important role that magnesium plays in the regulation of mineral metabolism in pregnancy and in particular the pregnancy complicated by pregestational diabetes. · Poor glycemic control during pregnancy leads to maternal magnesium deficiency.. · Maternal magnesium deficiency leads to fetal and neonatal magnesium deficiency.. · Neonatal magnesium deficiency leads to functional hypoparathyroidism and parathyroid hormone resistance..

BACKGROUND AND OBJECTIVES:Few studies have examined trends and disparities in long-term outcome after stroke in a representative US population. We used a population-based stroke study in the Greater Cincinnati Northern Kentucky region to examine trends and racial disparities in poststroke 5-year mortality. METHODS:All patients with acute ischemic strokes (AISs) and intracerebral hemorrhages (ICHs) among residents ≥20 years old were ascertained using ICD codes and physician-adjudicated using a consistent case definition during 5 periods: July 1993-June 1994 and calendar years 1999, 2005, 2010, and 2015. Race was obtained from the medical record; only those identified as White or Black were included. Premorbid functional status was assessed using the modified Rankin Scale, with a score of 0-1 being considered "good." Mortality was assessed with the National Death Index. Trends and racial disparities for each subtype were analyzed with logistic regression. RESULTS:We identified 8,428 AIS cases (19.3% Black, 56.3% female, median age 72) and 1,501 ICH cases (23.5% Black, 54.8% female, median age 72). Among patients with AIS, 5-year mortality improved after adjustment for age, race, and sex (53% in 1993/94 to 48.3% in 2015, overall effect of study year p = 0.009). The absolute decline in 5-year mortality in patients with AIS was larger than what would be expected in the general population (5.1% vs 2.8%). Black individuals were at a higher risk of death after AIS (odds ratio [OR] 1.23, 95% CI 1.08-1.39) even after adjustment for age and sex, and this effect was consistent across study years. When premorbid functional status and comorbidities were included in the model, the primary effect of Black race was attenuated but race interacted with sex and premorbid functional status. Among male patients with a good baseline functional status, Black race remained associated with 5-year mortality (OR 1.4, 95% CI 1.1-1.7, p = 0.002). There were no changes in 5-year mortality after ICH over time (64.4% in 1993/94 to 69.2% in 2015, overall effect of study year p = 0.32). DISCUSSION:Long-term survival improved after AIS but not after ICH. Black individuals, particularly Black male patients with good premorbid function, have a higher mortality after AIS, and this disparity did not change over time.

Introduction: Endovascular (EVT) eligibility estimates using population-based, NIH-funded Greater Cincinnati Northern Kentucky (GCNK) Stroke Study 2010 data have been reported. Given the evolving EVT landscape, we present updated estimates of annual EVT eligibility using the 2015 GCNK epidemiological data and extrapolate to the 2021 US census. We project the potential increase in eligible patients in the US for each possible expanded indication with a randomized trial currently planned/underway. Methods: We ascertained all hospitalized AIS patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Patients presenting within 0-5 hrs of last known well (LKW) were considered EVT eligible if they had a pre-stroke mRS<2, NIHSS ≥6 and ASPECTS ≥6. Those within 5-23 hrs of LKW were considered EVT-eligible if they had a pre-stroke mRS <3, NIHSS≥6, and favorable perfusion imaging. Expanded EVT eligible patients were defined as those with NIHSS <6, and pre-stroke mRS >1 (for 0-5 hrs) or ≥2 (for 5-23 hrs), or larger core. Estimates of vessel occlusion and favorable imaging were applied based on literature review and expert opinions. The derived estimates were age, race and sex-adjusted to the 2015 US adult population and extrapolated to 2021 population. Results: Among the 1.3 million total (1.05m adult) GCNK population in 2015, 2741 adults had an ischemic stroke and 2176 had data available for this analysis. A total of 1978 presented within 23 hrs of LKW, and 1233 within 0-5 hrs of LKW. Further results are outlined in the figure. Conclusions: It is estimated 18,484 adult patients in the US in 2021 meet strict EVT eligibility criteria. An estimated 15,699 patients with low NIHSS, 9621 with unfavorable imaging, and 28,107 with pre-stroke disability may become eligible for EVT in the future annually. US stroke systems should be optimized to handle all EVT-eligible stroke patients both now and in the future.

Objective: To review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs) Study Design: Retrospective review of all PPG work on glycemic control at different pregnancy timepoints and its association with embryonic, fetal and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction (IUGR), macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia and polycythemia. Results: we found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth; whereby early growth delay was followed by enhanced fetal growth which was associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. Conclusion: The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor.

Background: Monitoring changes in ischemic stroke severity at the population level is important as changes in risk factors and clinical treatments could influence stroke severity. We describe trends in the distribution of NIHSS across 3 time periods in a population-based epidemiologic stroke study. Methods: In 2005, 2010, and 2015 all adult acute ischemic strokes occurring within the Greater Cincinnati area presenting to 15 hospitals were ascertained using discharge codes (ICD-9 433-436; IDC-10 I63-I68, G45-46). Following physician verification, confirmed ischemic stroke cases underwent chart abstraction including estimation of a retrospective (rNIHSS) score at presentation. Descriptive statistics (rNIHSS median, IQR) were generated by survey year, demographics, and medical history. Using a binary definition of stroke severity (median rNIHSS score > 4 versus < 4), multivariable logistic regression was used to estimate changes in stroke severity over time, adjusting for potential confounders. Random effects were used to account for multiple admissions occurring in the same subject. Results: The number of ischemic stroke admissions in the 2005, 2010, and 2015 surveys was 1778, 1903, and 1933, respectively (Table). The median (IQR) rNIHSS scores were 3 (2-7), 3 (1-6), and 2 (1-6) across the 3 surveys, respectively; the proportion of admissions with rNIHSS > 4 was 48%, 39% and 37%, respectively. After adjusting for demographics, medical history and pre-stroke function, compared to 2005, the odds ratio for more severe stroke was 0.69 (95% CI= 0.60-0.79, p=0.001) in 2010 and 0.63 (95% CI= 0.55-0.73, p=0.001) in 2015. Conclusions: In this population- based study there was a statistically significant change in the severity of ischemic stroke hospitalizations with increases in the proportion of milder strokes over time. Potential reasons for this change need to be explored but could include changes in risk factors, clinical treatments or diagnostic approach.

BACKGROUND:Outreach campaigns have sought to reduce the burden of stroke by improving knowledge of stroke risk factors (RF) and warning signs (WS). We describe trends in stroke knowledge from 1995 to 2021. METHODS:From 1995 to 2021, 6 separate surveys were conducted in the Greater Cincinnati Northern Kentucky Region. Temporal trends in RF/WS knowledge were analyzed using logistic regression adjusting for Race, sex, age, and education. RESULTS:In 1995, 28.6% of participants (537/1880) could name ≥2 WS, compared with 50.6% (983/1944) in 2021 (trend P<0.0001 after adjustment). In 1995, 44.5% of participants (836/1880) knew ≥2 RF, compared with 56.7% (1103/1944) in 2021 (trend P<0.0001 after adjustment). Although still improved compared with 1995, fewer participants could identify ≥2 RF in 2021 (1103/1944, 56.7%) when compared with 2011 (1287/2036, 63.2%, pairwise P<0.05). This decline in RF knowledge was disproportionately larger in women (odds ratio of 0.67 for knowledge in 2021 compared with 2011 in females, P=0.047 for the interaction between sex and study year). CONCLUSIONS:Although stroke knowledge has overall improved since 1995, there is evidence for lost gains since 2011, particularly in women. Stroke outreach campaigns need ongoing evaluation.

Objective: To determine the frequency of gastric sensory motor symptoms in youth with type 1 diabetes. Methods: A prospective cross-sectional study was performed to evaluate symptoms of delayed gastric emptying in participants with type 1 diabetes, aged 12 to 25 years, using the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. In addition, a 5-year (January 2015 to December 2019), a retrospective study was completed on all gastric emptying scans performed in youth at our institution. Results: A total of 359 participants (mean age, 17.7 +/- 3.33 years) with type 1 diabetes completed the GCSI questionnaire. Compared with nonresponders, responders were more likely to be non-Hispanic White (90% vs 86%; P =.003) and female patients (58% vs 44%; P <.0001), with a lower HbA1c (8.1 +/- 1.8 vs 9.0 +/- 2.1; P <.0001). At least 1 gastrointestinal symptom was reported in 270 (75%) of responders, of which nausea was the most common (71%). A GCSI score of >= 1.9 suggestive of more severe gastrointestinal symptoms was reported in 17% of responders. Participants with scores >= 1.9 were older (19.1 +/- 3.0 vs 17.8 +/- 3.3 years; P =.01). In the retrospective study, 778 underwent gastric emptying scan, 29 participants had type 1 diabetes and 11 (38%) showed delayed gastric emptying. Conclusion: Gastrointestinal symptoms related to gastric sensory motor abnormalities are seen in youth and young adults with type 1 diabetes. In particular, for those with higher GCSI scores, earlier recognition and referral may be warranted.

Background and ObjectivesThere is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.MethodsThis is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model.ResultsA total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%; p = 0.0005) and increased intravenous drug users (8.3% vs 44.0%; p = 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p = 0.001).DiscussionFrom 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.