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Objective We aimed to establish a comprehensive digital phenotype for postpartum hemorrhage (PPH). Current guidelines rely primarily on estimates of blood loss, which can be inaccurate and biased and ignore complementary information readily available in electronic medical records (EMR). Inaccurate and incomplete phenotyping contributes to ongoing challenges in tracking PPH outcomes, developing more accurate risk assessments, and identifying novel interventions. Materials and Methods We constructed a cohort of 71 944 deliveries from the Mount Sinai Health System. Estimates of postpartum blood loss, shifts in hematocrit, administration of uterotonics, surgical interventions, and diagnostic codes were combined to identify PPH, retrospectively. Clinical features were extracted from EMRs and mapped to common data models for maximum interoperability across hospitals. Blinded chart review was done by a physician on a subset of PPH and non-PPH patients and performance was compared to alternate PPH phenotypes. PPH was defined as clinical diagnosis of postpartum hemorrhage documented in the patient’s chart upon chart review. Results We identified 6639 PPH deliveries (9% prevalence) using our phenotype—more than 3 times as many as using blood loss alone (N = 1,747), supporting the need to incorporate other diagnostic and intervention data. Chart review revealed our phenotype had 89% accuracy and an F1-score of 0.92. Alternate phenotypes were less accurate, including a common blood loss-based definition (67%) and a previously published digital phenotype (74%). Conclusion We have developed a scalable, accurate, and valid digital phenotype that may be of significant use for tracking outcomes and ongoing clinical research to deliver better preventative interventions for PPH.

Objective Genomics is increasingly used for diagnostic testing in children. This study describes the expectations of parents whose child received genomic testing and whether or not they were met. Methods A diverse stratified, purposive sample of parents of 22 children in New York City was interviewed using a semi-structured guide. Genomic test results were positive, negative, or uncertain. Results Parents expressed their expectations in narrative and numeric fashion. Parents expected that their child’s test would have a direct effect on their child’s diagnosis. Some believed that results would be definitive, while others recognized testing limitations. Expectations reflected parents’ hope to find a diagnosis and led to disappointment when results were uninformative or did not impact clinical management. Conclusion Results suggest pre-test genetic counseling emphasize the low likelihood of actionable results; however, parents’ expectations of genomics’ diagnostic capabilities are strongly rooted in their need to end the diagnostic odyssey and may be difficult to manage. Practice Implications Parents’ hope for a resolution and effective treatment for their child is a powerful context in which genetic counseling is heard. Clinicians who provide genomic testing should continue to acknowledge parents’ preconceptions. Additional research in other settings will help understand how to best address and manage parent expectations of genomic medicine.

Objective Postpartum hemorrhage (PPH) remains a leading cause of preventable maternal mortality in the United States. We sought to develop a novel risk assessment tool and compare its accuracy to tools used in current practice. Materials and Methods We used a PPH digital phenotype that we developed and validated previously to identify 6639 PPH deliveries from our delivery cohort (N = 70 948). Using a vast array of known and potential risk factors extracted from electronic medical records available prior to delivery, we trained a gradient boosting model in a subset of our cohort. In a held-out test sample, we compared performance of our model with 3 clinical risk-assessment tools and 1 previously published model. Results Our 24-feature model achieved an area under the receiver-operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.69-0.72), higher than all other tools (research-based AUROC, 0.67 [95% CI, 0.66-0.69]; clinical AUROCs, 0.55 [95% CI, 0.54-0.56] to 0.61 [95% CI, 0.59-0.62]). Five features were novel, including red blood cell indices and infection markers measured upon admission. Additionally, we identified inflection points for vital signs and labs where risk rose substantially. Most notably, patients with median intrapartum systolic blood pressure above 132 mm Hg had an 11% (95% CI, 8%-13%) median increase in relative risk for PPH. Conclusions We developed a novel approach for predicting PPH and identified clinical feature thresholds that can guide intrapartum monitoring for PPH risk. These results suggest that our model is an excellent candidate for prospective evaluation and could ultimately reduce PPH morbidity and mortality through early detection and prevention.

OBJECTIVE We previously reported a high (˜30%) but stable prevalence of diabetic ketoacidosis (DKA) at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth RESEARCH DESIGN AND METHODS We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010–2016) (n = 7,612 incident diabetes cases; mean [SD] age 10.1 [4.5] at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (RR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH for Diabetes in Youth Study site. RESULTS DKA prevalence increased from 35.3% (95% CI 32.2, 38.4) in 2010 to 40.6% (95% CI 37.8, 43.4) in 2016 (Ptrend = 0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR 1.02 [95% CI 1.01, 1.04] and adjusted RR 1.02 [95% CI 1.01, 1.04]; P = 0.01 for both). CONCLUSIONS Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002 to 2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time.

To determine the frequency of gastric sensory motor symptoms in youth with type 1 diabetes.A prospective cross-sectional study was performed to evaluate symptoms of delayed gastric emptying in participants with type 1 diabetes, ages 12 to 25 years, using the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. Additionally, a 5 year (1/2015-12/2019), retrospective study was completed on all gastric emptying scans (GES) performed in youth at our institution.A total of 359 participants (mean age 17.7±3.33 years) with type 1 diabetes completed the GCSI questionnaire. Compared with non-responders, responders were more likely to be non-Hispanic white (90% vs 86%, p=.003) and female (58% vs 44%, p0.0001) with a lower HbA1c (8.1±1.8 vs. 9.0±2.1, p0.0001). At least one GI symptom was reported in n=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=0.01). In the retrospective study (n=778) underwent GES, 29 participants had type 1 diabetes and 11 (38%) were found to have delayed gastric emptying.Gastrointestinal symptoms related to gastric sensory motor abnormalities are seen in youth and young adults with type 1 diabetes. Especially for those with higher GCSI scores, earlier recognition and referral may be warranted.

To assess changes in diabetes autoantibodies (DAs) over time in children and young adults with diabetes and determine whether observed changes were associated with demographic characteristics, clinical parameters and diabetes complications. Participants had DAs measured at baseline (10.3 ± 7.1 months after diabetes diagnosis) and at 12, 24 months and ≥5 years after the baseline measurement. At the ≥5-year follow-up, the presence of diabetes complications was assessed. We examined the associations between change in number of positive DAs and changes in individual DA status with the participants' characteristics and clinical parameters over time. Out of 4179 participants, 62% had longitudinal DA data and 51% had complications and longitudinal DA data. In participants with ≥1 baseline positive DA (n = 1699), 83.4% remained positive after 7.3 ± 2.3 years duration of diabetes. Decrease in number of positive DAs was associated with longer diabetes duration (p = 0.003 for 1 baseline positive DA; p 0.001 for 2 baseline positive DAs) and younger age at diagnosis (p 0.001 for 2 baseline positive DAs). No associations were found between change in number of positive DAs in participants with ≥1 baseline positive DA (n = 1391) and HbA1c, insulin dose, acute, or chronic complications after 7.7 ± 1.9 years duration of diabetes. DA status likely remains stable in the first 7 years after diabetes diagnosis. Younger age at diabetes diagnosis and longer duration were associated with less persistence of DAs. Measuring DAs after initial presentation may aid in diabetes classification but not likely in predicting the clinical course.

The authors review studies on key issues in women's health with potential impact on internal medicine practice. The reviewed articles discuss cardiovascular disease risks, bone health, breast cancer genetics, cervical cancer prevention, depression in the peripartum period, pelvic pain, and emergency contraception.

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

Successful retirement planning critically depends on access to accurate and up-to-date information. In this paper, we focus on the Australian Superannuation industry to examine the influence of digital technology in facilitating communication and information flow among its various actors. Using a qualitative research methodology, we conducted 22 semi-structured interviews with various industry actors including Superfunds, fund members, consultants, IT and digital solutions providers, and representatives from industry regulators. Our findings highlight the need for these actors to enhance their resource and knowledge-sharing capabilities, consumer need recognition, and information flow to ultimately enable Superfund members to improve their retirement planning and financial well-being. JEL Classification: D14 Household Saving • Personal Finance, D15 Intertemporal Household Choice • Life Cycle Models and Saving, J26 Retirement • Retirement Policies and J32 Nonwage Labor Costs and Benefits • Retirement Plans • Private Pensions

ObjectiveWe aimed to evaluate the efficacy of PrEP (pre-exposure prophylaxis) training sessions for OBGYN (obstetrician gynaecologist) providers given underutilisation of PrEP among women despite a high HIV burden.MethodsThree separate training sessions were held for providers in the OBGYN department at an academic medical centre in New York City from 2019 to 2021. The 1-hour training sessions were conducted by HIV specialists as in-person lectures or online live lectures. Participants were surveyed after the training on metrics of PrEP awareness, knowledge and comfort with management. Two-sample t-tests were used to compare difference in proportions of binomial variables and difference in means of Likert-scored answers pretraining and post-training events.Results63 respondents completed the surveys. There were low rates (13%) of past PrEP prescription among the respondents, while awareness of PrEP as an HIV prevention strategy was high before (95%) and after (98%) the training. After the training, there was an increase in understanding the epidemiology of HIV transmission (40% to 97%, pConclusionImplementation of PrEP training courses for OBGYN providers increased knowledge and comfort in identifying and managing patients who may benefit from PrEP services. Increasing training among OBGYN providers serving women at risk for HIV infection is an effective tool to narrow gaps in PrEP access.

Objective: Pulse wave analysis estimates arterial wave reflections relating to left ventricular dysfunction and cardiovascular event risk in adults. Forward and backward waves (Pf and Pb) may improve risk stratification for cardiovascular events. Data in youth are lacking. We hypothesized that a significant difference in wave reflections would be identified in young subjects with adverse cardiovascular risk factors. Approach and Results: Vital signs and labs were obtained in 551 patients aged 10 to 24 years who were lean (L=199), obese (O=173), or had type 2 diabetes (T=179). Wave separation was performed. Differences in cardiovascular risk factors and wave reflections were assessed using ANOVA. General linear models were constructed to elucidate independent predictors of wave reflections. O and T subjects had an adverse cardiovascular risk profile versus L. O and T subjects had higher Pf and Pb versus L ( P ≤0.05). When adjusted for adiposity and other cardiovascular risk factors, reflection magnitude increased from L to O to T with higher T versus L values ( P ≤0.05) and near-significant O versus L values ( P =0.06). Adiposity and blood pressure were major determinants of wave reflections. Pb influenced log left ventricular mass index, log E/e′, and log composite carotid intima-media thickness. Conclusions: Adolescents and young adults with obesity and type 2 diabetes have altered forward and backward wave reflections versus lean controls related to adiposity, BP, and insulin levels. These parameters may help risk stratify patients with adverse cardiovascular risk factors.

States often use covert operations to undermine their adversaries. This strategy involves, among other methods, intelligence organizations directing and supporting the operations of covert networks residing within the target state. This was a common occurrence during the Cold War, but covert clients also operate in modern conflicts in Syria, Ukraine, and elsewhere. This paper introduces and defines covert clients as a distinct and novel concept. We then use original data on more than 250 clandestine networks within the French Resistance to investigate the determinants of covert client success and failure. We find that clients founded by foreign operatives inserted into the target state fail at significantly higher rates than those that establish themselves organically within the target state, although this effect diminishes among stronger groups. We corroborate these findings with a case study of the Prosper network to demonstrate how clandestine group origins influence their local knowledge, incentives, and security practices. This study uses original data to provide novel insights into clandestine group survival by linking survival to group origins. In demonstrating the potential utility of focusing on the conduct of covert operations, we also contribute to a rapidly growing international relations literature on how states project power through covert action.

Background This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (32P) implantation in locally advanced pancreatic adenocarcinoma (LAPC). Methods Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and 18F-2-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography–computed tomography were performed and repeated after 12 weeks to assess treatment response. Following two cycles of conventional chemotherapy, patients underwent EUS-guided 32P implantation followed by six chemotherapy cycles. Results 12 patients with LAPC (median age 69 years [interquartile range 61.5–73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm3 (95 % confidence interval 4.95–10.85; P = 0.003), with minimal or no 18FDG uptake in nine patients (75 %). Tumor downstaging was achieved in six patients (50 %), leading to successful resection in five (42 %), including four R0 resections (80 %). Conclusions EUS-guided 32P implantation was feasible, well tolerated, and resulted in a 42 % surgical resection rate. Further evaluation in a larger randomized multicenter trial is warranted.

An alternative approach toward understanding and advancing hydrogel-based single walled carbon nanotube (SWNT) purification is described and employed. Experimental and atomistic modeling analysis of the leading hydrogel for SWNT purification, Sephacryl S200, affords creation of gels that mimic its behavior in terms of dependent SWNT interaction and SWNT purification properties. This achievement introduces a generalized approach toward optimization of SWNT purification media with respect to the components of Sephacryl. Here, the role of the radical initiator ammonium persulfate (APS) in hydrogel-based SWNT purification is explored through synthesis and characterization of gels containing varied APS concentration, and thus, varied amounts of covalently embedded charged organosulfate groups (R–SO4-). The presence of these moieties plays a significant role in SWNT-gel interactions: at decreasing APS concentration SWNT uptake is increased, the chiral profiles of purified SWNT are altered, and a greater fraction of adsorbed material is recovered. Tailored hydrogels containing minimal APS exhibit improved SWNT adsorption vs. Sephacryl. These findings warrant proposition of a four-step qualitative model that deconvolutes electrostatic and steric effects within SWNT/surfactant/hydrogel systems. Collectively, this work demonstrates enhanced methodology for hydrogel-based SWNT purification and lays the foundation for further optimization of the gel medium.

OBJECTIVETo evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents.RESEARCH DESIGN AND METHODSWe analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (RESULTSAdults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total; all P < 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P < 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total; all P < 0.05) than those in food secure households.CONCLUSIONSScreening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia.

Reconciling palaeodata with model simulations of the Pliocene climate is essential for understanding a world with atmospheric CO2 concentration near 400 ppmv (parts per million by volume). Both models and data indicate an amplified warming of the high latitudes during the Pliocene; however, terrestrial data suggest that Pliocene northern high-latitude temperatures were much higher than can be simulated by models. We focus on the mid-Pliocene warm period (mPWP) and show that understanding the northern high-latitude terrestrial temperatures is particularly difficult for the coldest months. Here the temperatures obtained from models and different proxies can vary by more than 20 ∘C. We refer to this mismatch as the “warm winter paradox”. Analysis suggests the warm winter paradox could be due to a number of factors including model structural uncertainty, proxy data not being strongly constrained by winter temperatures, uncertainties in data reconstruction methods, and the fact that the Pliocene northern high-latitude climate does not have a modern analogue. Refinements to model boundary conditions or proxy dating are unlikely to contribute significantly to the resolution of the warm winter paradox. For the Pliocene high-latitude terrestrial summer temperatures, models and different proxies are in good agreement. Those factors which cause uncertainty in winter temperatures are shown to be much less important for the summer. Until some of the uncertainties in winter high-latitude Pliocene temperatures can be reduced, we suggest a data–model comparison should focus on the summer. This is expected to give more meaningful and accurate results than a data–model comparison which focuses on the annual mean.

Objectives. We compared arterial stiffness and heart rate variability (HRV) over time by diabetes type and determined the risk factors associated with worsening arterial stiffness and HRV in young adults with youth-onset diabetes. Research Design and Methods: Arterial stiffness (pulse wave velocity, augmentation index) and six indices of heart rate variability were measured twice, 4.5 years apart among participants with either youth-onset type 1 or type 2 diabetes in the SEARCH for Diabetes in Youth Study. Multivariable linear regression models assessed risk factors associated with arterial stiffness and HRV at follow-up assessment. Results. Of 1159 participants studied, 949 had type 1 (mean age 17.1 ± 4.7 years, 60.3% non-Hispanic White, 55% female) and 210 had type 2 diabetes (mean age 22.1 ± 3.5 years, 23.8% non-Hispanic White, 71% female) at initial assessment when diabetes duration was 7.9 years (both groups). Participants with type 2 vs type 1 diabetes had greater vascular stiffness and more abnormalities in HRV at initial and follow-up assessment and a greater change over time (all p Conclusions. Arterial stiffness and HRV worsened over time with greater changes among those with type 2 compared with type 1 diabetes, and among those with features of the metabolic syndrome. The risk factor profile documents potentially modifiable pathways to prevent or limit cardiovascular complications in young adults with youth-onset diabetes.

Although household food insecurity (HFI) has been associated with depressive symptoms in youth and young adults (YYA) with youth-onset diabetes, little is known about the association of HFI with other mental health comorbidities. We examined the association of HFI with stress and anxiety symptoms among YYA with diabetes using cross-sectional data from the SEARCH Food Security Cohort study (assessments conducted 2018-2020; n = 1030, age =23.8± 0.3, female =58.8%, type 1 diabetes (T1D) = 881, type 2 diabetes (T2D) =149) . HFI was defined as 3+ affirmations on the USDA Household Food Security Survey Module. The Generalized Anxiety Disorder (GAD-7) and Cohen’s Perceived Stress Scale (PSS-14) were used to assess outcomes of anxiety (score range 0-21) and stress (score range 0-56) , higher scores indicating greater anxiety or stress. Linear regression models were adjusted for age, sex, race/ethnicity, site, diabetes duration, parental education, income, and whether assessment was completed pre/post the coronavirus pandemic. Analyses were stratified by diabetes type. HFI was present in 17.3% of T1D and 35.6 % of T2D. Moderate/severe anxiety symptom scores (range 10-21) were found in 27.5 % (mean=6.9, s.d. =5.5) of T1D and 40.9% (mean=8.4, s.d. =6.5) of T2D. Mean stress scores were 26.7 (s.d.=6.3) for T1D and 27.9 (s.d.=6.3) for T2D. In T1D, HFI was associated with higher anxiety (β=4.8, p= Disclosure A.D.Brown: n/a. S.M.Marcovina: None. C.Pihoker: None. A.D.Liese: None. J.A.Mendoza: None. E.A.Frongillo: None. K.Flory: None. B.A.Reboussin: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. L.M.Dolan: None. A.Bellatorre: None. F.Malik: n/a. Funding NIH/NIDDK (1R01DK117461-01) ; NIH/NIDDK/CDC (1UC4DK108173) ; NIH/NIGMS (T32-GM081740)

We examined the association between diabetes stigma, sociodemographic and psychosocial variables in AYAs with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth study, 2016-2019. A 5-question survey assessed frequency of perceived stigma experience, from which we created a total stigma score. We used multivariable modeling to examine these associations adjusting for sex, race/ethnicity, age, clinic site, diabetes duration, education level, health insurance type, treatment regimen, and HbA1c levels. Analyses were stratified by diabetes type. Of the 1,6AYAs who completed the stigma survey, 78% had T1D, 56% were female, and 48% were non-Hispanic White. Mean (SD) age at study visit was 21.7 (5.1) years (range - 24.9 years) . Mean (SD) HbA1c level was 9.2% (2.3) . Participants with T1D with lower household income had higher stigma scores compared to those with higher household income (p=0.03) . Among AYAs with T1D or T2D, higher stigma score was associated with food insecurity (p< 0.01) , disordered eating behaviors (p < 0.01) , depressive symptoms (p < 0.01) , and decreased AYA (p Disclosure K.B.Eitel: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. A.D.Liese: None. S.M.Marcovina: None. E.J.Mayer-davis: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.J.Roberts: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. R.A.Bell: None. A.Bellatorre: None. C.E.Barrett: None. A.Cristello: None. D.Dabelea: None. L.M.Dolan: None. Funding The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention.

We sought to determine incidence rates for micro- and macrovascular events in youth-onset type 1 (T1D) and type 2 (T2D) diabetes in the SEARCH (T1D: N=564; T2D: N=149) and TODAY (T2D: N=495) studies. At study visits, we ascertained self-reported ophthalmologic, kidney, neuropathy, cardiac, and peripheral and cerebrovascular events , obtained medical records for these events, and adjudicated each event using predetermined standardized and harmonized criteria. Data were available from more than 6,000 person-years in T1D and more than 8,000 person-years in T2D. Incidence rates (events per 10,000 person-years) were calculated. As shown in the table, despite similar mean diabetes duration of 10-13 years and mean HbA1c >9%, the incidence of reported complications was higher in the youth with T2D than those with T1D, with rates 2.5-fold higher for microvascular and 4.0-fold higher for macrovascular disease. These data support the aggressive nature of youth-onset T2D. Disclosure A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. S.Isom: None. J.B.Tryggestad: None. R.Gubitosi-klug: None. L.M.Dolan: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. K.Drews: None. Funding National Institutes of Health DK061230; R01DK127208 Center for Disease Control

We examined the association between diabetes stigma and glycemic control, treatment regimen, and acute and chronic complications in adolescents and young adults (AYAs) with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth Study, 2016-2019. A 5-question survey assessed frequency of perceived stigma experience, from which we created a total stigma score. We used multivariable linear modeling, stratified by T1D and T2D, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic, clinic site, duration of diabetes, health insurance type, treatment regimen, and HbA1c. Of 16respondents, 78% had T1D, 56% were female, and 48% were non-Hispanic White. Mean (SD) age at study visit was 21.7 (5.1) years (range - 24.9 years) . Mean (SD) HbA1c was 9.2% (2.3) . Higher stigma scores were associated with female sex and higher HbA1c (both p Disclosure K.B.Eitel: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. A.D.Liese: None. S.M.Marcovina: None. E.J.Mayer-davis: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.J.Roberts: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. R.A.Bell: None. A.Bellatorre: None. C.E.Barrett: None. A.Cristello: None. D.Dabelea: None. L.M.Dolan: None. Funding The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention.

Arterial stiffness and echocardiograms were assessed in participants with youth-onset DM (N=399, 22.8 ± 5.1 years, duration 10.8 ± 3.2 years, 63% female, 45% non-Hispanic White; 33% non-Hispanic Black, 13.5% Hispanic, 8% Other, 44% type 2 DM (T2D)) . Cardiovascular risk factors (CVRF) , arterial stiffness and cardiac measures were compared between those with or without elevated arterial stiffness (stiff = Pulse Wave Velocity [PWV] ≥ 90th% for lean controls) . Association between PWV and cardiac parameters after adjusting for CVRF was assessed. Participants with high PWV were 4.6 yrs older, had 0.6 yrs longer diabetes duration, were more likely to be female (71.5 vs. 54.9%) , non-Hispanic White (68.8 v 42.3) , have T2D (72.0 v 20.2%) , higher BMI (35.6 v 26.3 kg/m2) , BP (122/79 v 109/72 mmHg) , LDL-C (113 v 100 mg/dl) , CRP (0.6 v 0.1mg/dL) , and HbA1c (9.6 v 8.9%; all p≤0.04) . Those with high PWV had higher left ventricular mass index (LVMI) and lower systolic and diastolic function. PWV remained a significant predictor of LVMI (R2 0.37) , systolic (EF, R2 0.235) and diastolic (e’/a’, R2 0.461) function after adjustment for CVRF, all p≤0.0002. Higher arterial stiffness is associated with adverse changes in cardiac structure and function and was more prevalent in persons with T2D compared to type 1 DM. Disclosure E.M. Urbina: Advisory Panel; Astellas Pharma Inc. D. Dabelea: None. R. Dagostino Jr: None. S.R. Daniels: None. L.M. Dolan: None. G. Imperatore: None. E. Lustigova: None. S.M. Marcovina: None. A.K. Mottl: Advisory Panel; Bayer AG. Board Member; Bayer AG. Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. C. Pihoker: None. A.S. Shah: None. Funding Grant Support (SEARCH 4) : The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention. The Population Based Registry of Diabetes in Youth Study (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, and U18DP006139) is funded by the Centers for Disease Control and Prevention (DP-15-002) and supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Grant Support (SEARCH 1, 2, 3) : SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Kaiser Permanente Southern California (U48/CCU919219, UDP000246, and U18DP002714) , University of Colorado Denver (U48/CCU819241-3, UDP000247, and U18DP000247-06A1) , Cincinnati's Children's Hospital Medical Center (U48/CCU519239, UDP000248, and 1U18DP002709) , University of North Carolina at Chapel Hill (U48/CCU419249, UDP000254, and U18DP002708) , Seattle Children's Hospital (U58/CCU019235-4, UDP000244, and U18DP002710-01] and Wake Forest University School of Medicine (U48/CCU919219, UDP000250, and 200-2010-35171) .

To examine CRF trends that may impact future CVD risk, the SEARCH study assessed CRF for diabetes-related complications in incident cohorts established from 2002 - 2016. Linear regression was used to assess trends over each incident year for non-HDL-c, LDL-c, VLDL-c, TG, BMI z-score, systolic and diastolic blood pressure (BP) z-scores, albumin/creatinine ratio (ACR) and eGFR. Models were stratified by diabetes type (Type 1, N=4600; Type 2, N=932) , adjusted for age at diagnosis, sex, DM duration and race/ethnicity. An interaction analysis was conducted to assess differential time trends by type. For youth with type 1, non-HDL-c, BP, BMI and ACR >30 decreased while HDL-c increased over time. For youth with type 2, non-HDL-c, and eGFR decreased, and BMI increased over time (table) . Significant time change interactions by type were seen for HDL-c and for BMI z-score and BP measures (table) .We observed small but significant changes in several CRFs over time in youth with incident DM, especially lipids, with greater improvements seen in youth with type 1. Youth with type 2 had worsening trends over time in BMI, BP, and kidney function. Further research is needed to better understand these trends and their implications for long term CVD risk. Disclosure R.A.Bell: None. A.D.Liese: None. E.Lustigova: None. S.M.Marcovina: None. L.Merjaneh: None. D.J.Pettitt: n/a. C.Pihoker: None. A.S.Shah: None. A.M.South: None. L.E.Wagenknecht: None. J.Rigdon: None. A.Bellatorre: None. D.Dabelea: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. J.Divers: None. L.M.Dolan: None. G.Imperatore: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. Funding Centers for Disease Control and Prevention U18DP006131

Limited data exist examining arterial stiffness and heart rate variability (HRV) over time in young adults with youth-onset type 1 (T1D) and type 2 diabetes (T2D) . We compared arterial stiffness and HRV over time and by diabetes type and determined the risk factors associated with worsening arterial stiffness and HRV. Arterial stiffness (pulse wave velocity, augmentation index) and HRV (SDNN and PNN50) were measured twice (∼ 5 years apart) in the SEARCH for Diabetes in Youth Study. Linear regression models assessed risk factors overtime and with arterial stiffness and HRV at follow-up. Of 1159 participants studied, 949 had T1D (mean age 17.1 ± 4.7 years, 60.3% non-Hispanic White, 55% female) and 2had T2D (mean age 22.1 ± 3.5 years, 23.8% non-Hispanic White, 71% female) at initial assessment when diabetes duration was 7.9 years (both groups) . Participants with T2D vs. T1D had greater arterial stiffness and more abnormalities in HRV at initial and follow-up assessments (Figure) .For AIx and PNN50 T2D compared to T1D had a greater change over time (p Disclosure A.S. Shah: None. R. Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. L.M. Dolan: None. D. Dabelea: None. G. Imperatore: None. A.K. Mottl: Advisory Panel; Bayer AG. Board Member; Bayer AG. Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. E. Lustigova: None. C. Pihoker: None. S.M. Marcovina: None. E.M. Urbina: Advisory Panel; Astellas Pharma Inc. Funding NIH and CDC

The SEARCH study ascertained individuals with type 2 diabetes (T2D) diagnosed at Disclosure K. A. Sauder: None. A. Bellatorre: None. J. M. Lawrence: None. J. Divers: None. E. T. Jensen: Consultant; Regeneron Pharmaceuticals Inc. L. E. Wagenknecht: None. A. D. Liese: None. D. Dabelea: None. S. M. Marcovina: None. C. Pihoker: None. K. Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. A. S. Shah: None. L. M. Dolan: None. Funding Centers for Disease Control and Prevention and National Institutes of Health

We studied arterial stiffness in youth and young adults with T1D and potential longitudinal mediators of racial and ethnic disparities. SEARCH for Diabetes in Youth Study participants (n=2317; 14% Hispanic, 12% non-Hispanic Black, 74% non-Hispanic White) had CV risk factors (body size, lipid profile, blood pressure, A1c, urinary creatinine, pulse) measured 2-6 times from ∼9 months up to ˜years after T1D diagnosis. Arterial stiffness was measured with pulse wave velocity (PWV) at ˜years T1D duration (˜18 years of age) . For each risk factor, we summarized the longitudinal data as mean, max, slope, and area-under-the-curve (AUC) . Using split test/replication datasets, we a) identified the summary statistic for each risk factor most associated with PWV using flipped multivariate general linear models, and b) used the resulting statistics to construct a risk score predicting PWV with a stepwise general linear model. The final score included AUC for BMI, triglycerides and creatinine; heart rate slope; max mean arterial pressure; and age and T1D duration at PWV measurement, explaining 35% of variability in PWV at 18 years. PWV varied by race and ethnicity (Figure - left) . Adjustment for the risk score partially attenuated this disparity (Figure - right) . These data suggest CV risk factors from T1D diagnosis onward are related to racial and ethnic disparities in arterial stiffness, but other factors are likely involved. Disclosure K.A.Sauder: None. S.M.Marcovina: None. E.J.Mayer-davis: None. A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. C.Pihoker: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. A.S.Shah: None. E.M.Urbina: Advisory Panel; Astellas Pharma Inc. L.E.Wagenknecht: None. S.R.Daniels: None. D.Dabelea: None. D.H.Glueck: None. K.K.Harrall: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. L.M.Dolan: None. A.Lane-cordova: None. A.D.Liese: None. E.Lustigova: None. F.Malik: n/a. Funding National Institutes of Health

Use of HIV PrEP (pre-exposure prophylaxis) is a strategic tool in the effort to end the HIV epidemic. 20% of new HIV infections in the US are among cis-gender women, yet they comprise only 5% of all PrEP users. Black women disproportionately bear the burden of new HIV acquisition and accounted for almost 60% of new HIV diagnoses among women in 2018. Increasing understanding and uptake of PrEP among women at risk of HIV acquisition in alignment with their reproductive values and preferences is key to increasing PrEP uptake and decreasing HIV burden in this population.This study examines how experiences with contraception among women of color shape their perceptions and preferences regarding HIV PrEP to inform counseling that aligns with their reproductive values.Women aged 18-45 who self-identified as Black or Latina were recruited at an academic medical center in the Bronx from June 2018 to July 2019. We enrolled 30 participants seeking family planning care (10), prenatal care (10), or care for sexually transmitted infections (10). Participants completed a brief written survey assessing their risk of HIV acquisition. Semi-structured, face-to-face interviews were then audio-recorded, transcribed, and entered into Dedoose. Grounded theory and constant comparison approaches were used to analyze the data.Twenty-one participants (70%) screened positive for HIV acquisition risk. Four had received information on PrEP from a medical provider prior to the interview. Three themes emerged from the qualitative analysis: (1) Similar to oral contraception, women conceptualized PrEP as a "daily pill" to support their reproductive health; (2) Women perceived PrEP as a tool to support autonomy and pleasure in their sexual health; (3) Like birth control, women desired multiple delivery options for HIV prophylaxis.Contraception may serve as a frame of reference when counseling about PrEP among cis-women at risk of acquiring HIV. Our study suggests that this approach re-contextualizes counseling on PrEP within a sex-positive framework that prioritizes pleasure, safety, and autonomy as integral to sexual and reproductive wellness. Consideration of historically marginalized women's experiences with contraception and reproductive values may facilitate their use of PrEP.PrEP (pre-exposure prophylaxis) is a medicine taken daily by people at risk of getting HIV from sex or injection drug use. Although PrEP is a safe and effective medication for women, the use of PrEP remains exceedingly low among cis-gender women at risk of HIV in the US. This study examines how experiences with contraception among women of color, who disproportionately bear the burden of HIV acquisition, shape their perceptions and preferences regarding PrEP. We interviewed 30 women who self-identified as Black or Latina at an academic medical center in the Bronx. Similar to oral contraception, women in this study conceptualized PrEP as a “daily pill” to support their reproductive health. This report details how women’s experiences with contraception may serve as the foundation to re-contextualize conversations on PrEP within a sex-positive framework that prioritizes pleasure, safety, and autonomy as integral to sexual and reproductive wellness.

Summary Background One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors. Methods This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors. Findings 1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50 000 and did not have private health insurance. Interpretation Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity. Funding US Centers for Disease Control and Prevention, US National Institutes of Health.