Publications by authors named "Jeanette M Stafford"

52 Publications

Prevalence of Chronic Opioid Use in Patients with Peripheral Arterial Disease Undergoing Revascularization.

J Vasc Surg 2021 Aug 31. Epub 2021 Aug 31.

Wake Forest University School of Medicine, Department of Vascular and Endovascular Surgery, Winston-Salem, North Carolina.

Objectives: Opiate use, dependence, and the associated morbidity and mortality are major current public health problems in the United States. Little is known about patterns of opioid use in patients with peripheral arterial disease (PAD). The purpose of this study was to identify the prevalence of chronic preoperative and postoperative prescription opioid use in patients with PAD. A secondary aim was to determine the demographic, comorbid conditions, and operative characteristics associated with chronic opioid use.

Methods: Using a single-institution database of patients with PAD undergoing open or endovascular lower extremity intervention from 2013-2014, data regarding opiate use and associated conditions were abstracted for analysis. Patients were excluded if they did not live in North Carolina or surgery was not for PAD. Preoperative (PreCOU) and postoperative chronic opioid use (PostCOU) were defined as consistent opioid prescription filling in the three months before and after the index procedure, respectively. Opioid prescription filling was assessed using the North Carolina Controlled Substance Reporting System. Demographics, comorbid conditions, other adjunct pain medication data, and operative characteristics were abstracted from our institutional electronic medical record. Associations with PreCOU were evaluated using t-test, Wilcoxon test, or two sample median test (continuous), or chi-square or Fisher's exact test (categorical).

Results: 202 patients undergoing open [108 (53.5%)] or endovascular [94 (46.5%)] revascularization for claudication or critical limb ischemia were identified for analysis. Mean age was 64.6 years and 36% were female. Claudication was the indication for revascularization in 26.7% of patients and CLI was the indication in 73.3% of patients. Median preoperative ABI was 0.50. Sixty-eight patients (34%) met the definition for PreCOU. PreCOU was associated with female gender, history of chronic musculoskeletal pain, benzodiazepine use, and self-reported illicit drug use. Less than 50% of patients reported use of non-opiate adjunct pain medications. No association was observed between PreCOU and pre or postoperative ABI, or number of prior lower extremity interventions. Following revascularization, median ABI was 0.88. PreCOU was not associated with significant differences in postoperative complications, length of stay, or mortality. Overall, 71 patients (35%) met the definition for PostCOU, 14 of whom had no history of preoperative chronic opiate use. Ten patients with PreCOU did not demonstrate PostCOU.

Conclusions: Chronic opiate use was common in patients with PAD with a prevalence of approximately 35%, both prior to and following revascularization. Revascularization was associated with a termination of chronic opiate use in less than 15% of patients with PreCOU. Additionally, 10% of patients who did not use opiates chronically before their revascularization did so afterwards. Patients with PAD requiring intervention represent a high risk group with regards to chronic opiate use. Increased diligence in identifying opioid use among PAD patients and optimizing the use of non-narcotic adjunct pain medications may result in a lower prevalence of chronic opiate use and its attendant adverse effects.
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http://dx.doi.org/10.1016/j.jvs.2021.07.236DOI Listing
August 2021

Disparities in Hemoglobin A Testing During the Transition to Adulthood and Association With Diabetes Outcomes in Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

Diabetes Care 2021 Aug 10. Epub 2021 Aug 10.

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC.

Objective: To identify correlates of hemoglobin A (HbA) testing frequency and associations with HbA levels and microvascular complications in youth-onset diabetes.

Research Design And Methods: The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years (=1,885 type 1, =230 type 2) and 13 years (=649 type 1, = 84 type 2) diabetes duration. We identified correlates of reporting ≥3 HbA tests/year using logistic regression. We examined associations of HbA testing with HbA levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression.

Results: For type 1 diabetes, odds of reporting ≥3 HbA tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (odds ratio [OR] 0.91 [95% CI 0.88-0.95]), longer duration of diabetes (OR 0.90 [0.82-0.99]), not having a personal doctor (OR 0.44 [0.30-0.65]), and lapses in health insurance (OR 0.51 [0.27-0.96]). HbA testing ≥3 times/year over time was associated with lower HbA levels (OR -0.36% [-0.65 to -0.06]) and lower odds of microvascular complications (OR 0.64 [0.43-0.97]) at 13 years duration, but associations were attenuated after adjustment for HbA testing correlates (OR -0.17 [-0.46 to 0.13] and 0.70 [0.46-1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased the odds of reporting ≥3 HbA tests/year over time (OR 0.19 [0.06-0.63]), but HbA testing frequency was not associated with HbA levels or microvascular complications.

Conclusions: We observed disparities in HbA testing frequency predominately by health care-related factors, which were associated with diabetes outcomes in type 1 diabetes.
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http://dx.doi.org/10.2337/dc20-2983DOI Listing
August 2021

Glycemic control is associated with dyslipidemia over time in youth with type 2 diabetes: The SEARCH for diabetes in youth study.

Pediatr Diabetes 2021 Nov 15;22(7):951-959. Epub 2021 Aug 15.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA.

Background: Dyslipidemia has been documented in youth with type 2 diabetes. There is a paucity of studies examining dyslipidemia over time in youth with type 2 diabetes and associated risk factors.

Objective: To evaluate lipids at baseline and follow-up and associated risk factors in youth with type 2 diabetes.

Methods: We studied 212 youth with type 2 diabetes at baseline and after an average of 7 years of follow-up in the SEARCH for Diabetes in Youth Study. Abnormal lipids were defined as high-density lipoprotein cholesterol (HDL-C) < 35, low-density lipoprotein cholesterol (LDL-C) > 100, or triglycerides >150 (all mg/dl). We evaluated participants for progression to abnormal lipids (normal lipids at baseline and abnormal at follow-up), regression (abnormal lipids at baseline and normal at follow-up), stable normal, and stable abnormal lipids over time for HDL-C, LDL-C, and triglycerides. Associations between hemoglobin A1c (HbA1c) and adiposity over time (area under the curve [AUC]) with progression and stable abnormal lipids were evaluated.

Results: HDL-C progressed, regressed, was stable normal, and stable abnormal in 12.3%, 11.3%, 62.3%, and 14.2% of participants, respectively. Corresponding LDL-C percentages were 15.6%, 12.7%, 42.9%, and 28.8% and triglycerides were 17.5%, 10.8%, 55.7%, and 16.0%. Each 1% increase in HbA1c AUC was associated with a 13% higher risk of progression and stable abnormal triglycerides and a 20% higher risk of progression and stable abnormal LDL-C. Higher adiposity AUC was marginally (p = 0.049) associated with abnormal HDL-C.

Conclusions: Progression and stable abnormal LDL-C and triglycerides occur in youth with type 2 diabetes and are associated with higher HbA1c.
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http://dx.doi.org/10.1111/pedi.13253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530941PMC
November 2021

Increase in Prevalence of Diabetic Ketoacidosis at Diagnosis Among Youth With Type 1 Diabetes: The SEARCH for Diabetes in Youth Study.

Diabetes Care 2021 Jun 7. Epub 2021 Jun 7.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.

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 <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed.

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) ( = 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 ( = 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]; = 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.
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http://dx.doi.org/10.2337/dc20-0389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323183PMC
June 2021

Cognitive Function in Adolescents and Young Adults With Youth-Onset Type 1 Versus Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

Diabetes Care 2021 Apr 26. Epub 2021 Apr 26.

Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA.

Objective: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth study, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D ( = 1,095) or T2D ( = 285).

Research Design And Methods: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition.

Results: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; = 0.06) and Picture Vocabulary scores (model 3; = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model ( < 0.01 for all, respectively).

Conclusions: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.
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http://dx.doi.org/10.2337/dc20-2308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247514PMC
April 2021

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Nat Commun 2021 01 5;12(1):24. Epub 2021 Jan 5.

Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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http://dx.doi.org/10.1038/s41467-020-19366-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785747PMC
January 2021

Dietary strategies to manage diabetes and glycemic control in youth and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for diabetes in youth study.

Pediatr Diabetes 2020 11 23;21(7):1093-1101. Epub 2020 Aug 23.

Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado, Aurora, Colorado, USA.

Aims: Examine associations of dietary strategies used to manage diabetes over time with hemoglobin A1c in youth-onset type 1 or type 2 diabetes.

Methods: The SEARCH for Diabetes in Youth observational study assessed dietary strategies used by 1814 participants with diabetes (n = 1558 type 1, n = 256 type 2) at two to three research visits over 5.5 years (range 1.7-12.2). Participants reported often, sometimes, or never using 10 different dietary strategies, and use over time was categorized into five mutually exclusive groups: often using across visits; started using at later visits; sometimes using across visits; stopped using at later visits; or never using across visits. General multivariable linear models evaluated most recent A1c by use category for each strategy.

Results: In type 1 diabetes, A1c was lower among those who starting tracking calories (-0.4%, Tukey P < .05), often counted carbs (-0.8%, Tukey P < .001), or sometimes chose low glycemic index foods (-0.5%, Tukey P = .02) vs those with less use, while participants who never drank more milk had the lowest A1c (-0.5%, Tukey P = .04). In type 2 diabetes, A1c was lower among those who often limited high fat foods (-2.0%, Tukey P = .02) or started counting carbohydrates (-1.7%, Tukey P = .07) than those who did so less.

Conclusions: For several dietary strategies, more frequent use over time was related to lower A1c in youth-onset type 1 and type 2 diabetes, suggesting these strategies can likely support diabetes management for this population. Investigation into factors predicting receipt of advice for specific strategies and corresponding impact on intake might be considered.
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http://dx.doi.org/10.1111/pedi.13091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855046PMC
November 2020

The association of low-density lipoprotein cholesterol with elevated arterial stiffness in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth study.

Pediatr Diabetes 2020 08 5;21(5):863-870. Epub 2020 May 5.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA.

Aim: Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors.

Method: We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors.

Results: At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D.

Conclusions: Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.
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http://dx.doi.org/10.1111/pedi.13021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709736PMC
August 2020

Progression to hypertension in youth and young adults with type 1 or type 2 diabetes: The SEARCH for Diabetes in Youth Study.

J Clin Hypertens (Greenwich) 2020 05 15;22(5):888-896. Epub 2020 Apr 15.

Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.

Central obesity may contribute to the development of hypertension in youths with diabetes. The SEARCH for Diabetes in Youth Study followed 1518 youths with type 1 diabetes (T1D) and 177 with type 2 diabetes (T2D) diagnosed when <20 years of age for incident hypertension. Incident hypertension was defined as blood pressure ≥95th percentile (or ≥130/80 mm Hg) or reporting antihypertensive therapy among those without hypertension at baseline. Poisson regression models were stratified by diabetes type and included demographic and clinical factors, clinical site, and waist-to-height ratio (WHtR). Youths with T2D were more likely to develop hypertension than those with T1D (35.6% vs 14.8%, P < .0001). For each 0.01 unit of annual increase in WHtR, adjusted relative risk for hypertension was 1.53 (95% CI 1.36-1.73) and 1.20 (95% CI 1.00-1.43) for youths with T1D and T2D, respectively. Effective strategies targeted toward reducing central obesity may reduce hypertension among youths with diabetes.
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http://dx.doi.org/10.1111/jch.13849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383720PMC
May 2020

Receipt of recommended complications and comorbidities screening in youth and young adults with type 1 diabetes: Associations with metabolic status and satisfaction with care.

Pediatr Diabetes 2020 03 16;21(2):349-357. Epub 2019 Dec 16.

Department of Pediatrics, University of Washington, Seattle, Washington.

Objectives: This study sought to: (a) assess the prevalence of diabetes complications and comorbidities screening as recommended by the American Diabetes Association (ADA) for youth and young adults (YYAs) with type 1 diabetes (T1D), (b) examine the association of previously measured metabolic status related to diabetes complications with receipt of recommended clinical screening, and (c) examine the association of satisfaction with diabetes care with receipt of recommended clinical screening.

Methods: The study included 2172 SEARCH for Diabetes in Youth participants with T1D (>10 years old, diabetes duration >5 years). Mean participant age was 17.7 ± 4.3 years with a diabetes duration of 8.1 ± 1.9 years. Linear and multinomial regression models were used to evaluate associations.

Results: Sixty percent of participants reported having three or more hemoglobin A1c (HbA1c) measurements in the past year. In terms of diabetes complications screening, 93% reported having blood pressure measured, 81% having an eye examination, 71% having lipid levels checked, 64% having a foot exam, and 63% completing albuminuria screening in accordance with ADA recommendations. Youth known to have worse glycemic control in the past had higher odds of not meeting HbA1c screening criteria (OR 1.11, 95% CI = 1.05, 1.17); however, after adjusting for race/ethnicity, this was no longer statistically significant. Greater satisfaction with diabetes care was associated with increased odds of meeting screening criteria for most of the ADA-recommended measures.

Conclusions: Efforts should be made to improve diabetes complications screening efforts for YYAs with T1D, particularly for those at higher risk for diabetes complications.
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http://dx.doi.org/10.1111/pedi.12948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597528PMC
March 2020

Association of metformin and statin medications with surrogate measures of cardiovascular disease in youth with type 1 diabetes: the SEARCH for diabetes in youth study.

Ann Pediatr Endocrinol Metab 2019 Sep 30;24(3):187-194. Epub 2019 Sep 30.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.

Purpose: Youth with type 1 diabetes mellitus (T1DM) are at risk of cardiovascular disease (CVD). We evaluated if metformin or statin use was associated with surrogate measures of improved CVD.

Methods: We included participants from the SEARCH observational study. Participants treated with insulin plus metformin (n=42) or insulin plus statin (n=39) were matched with 84 and 78 participants, respectively, treated with insulin alone. Measures of arterial stiffness obtained were pulse wave velocity (PWV), augmentation index (AI75), and heart rate variability as standard deviation of the normal-to-normal interval (SDNN) and root mean square differences of successive NN intervals (RMSSD).

Results: CVD measures were not significantly different among participants on insulin plus metformin versus those on insulin alone: PWV (5.9±1.0 m/sec vs. 5.8±1.5 m/sec, P=0.730), AI75 (1.8 [-6.0 to 8.0] vs. -2.4 [-10.7 to 3.8], P=0.157), SDNN (52.4 [36.8-71.1] m/sec vs. 51.8 [40.1-74.9] m/sec, P=0.592), and RMSSD (43.2 [29.4-67.6] vs. 47.4 [28.0-76.3], P=0.952). CVD measures were not different for statin users versus nonusers: PWV (5.7±0.8 m/sec vs. 5.9 ±1.1 m/sec, P=0.184), AI75 ( -4.0 [-9.5 to 1.7] vs. -6.7 [-11.3 to 5.7], P=0.998), SDNN (54.6 [43.5-77.2] m/sec vs. 63.1 [44.2-86.6] m/sec, P=0.369), and RMSSD (49.5 [31.2-74.8] vs. 59.2 [38.3-86.3], P=0.430).

Conclusion: We found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue.
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http://dx.doi.org/10.6065/apem.2019.24.3.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790871PMC
September 2019

Co-occurrence of early diabetes-related complications in adolescents and young adults with type 1 diabetes: an observational cohort study.

Lancet Child Adolesc Health 2019 01 6;3(1):35-43. Epub 2018 Nov 6.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.

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.
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http://dx.doi.org/10.1016/S2352-4642(18)30309-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295346PMC
January 2019

COMPASS-CP: An Electronic Application to Capture Patient-Reported Outcomes to Develop Actionable Stroke and Transient Ischemic Attack Care Plans.

Circ Cardiovasc Qual Outcomes 2018 08;11(8):e004444

Department of Neurology (P.W.D., R.M.A., C.N.C., S.L.L., M.E.S., C.D.B.).

Background Patient-reported outcomes (PROs) are clinical tools that measure patients' goals of care and assess patient-reported physical, mental, and social well-being. Despite their value in advancing patient-centered care, routine use of PROs in stroke management has lagged. As part of the pragmatic COMPASS (Comprehensive Post-Acute Stroke Services) trial, we developed COMPASS-Care Plan (CP), a clinician-facing application that captures and analyzes PROs for stroke and transient ischemic attack patients discharged home and immediately generates individualized electronic CP. In this report, we (1) present our methods for developing and implementing COMPASS-CP PROs, (2) provide examples of CP generated from COMPASS-CP, (3) describe key functional, social, and behavioral determinants of health captured by COMPASS-CP, and (4) report on clinician experience with using COMPASS-CP in routine clinical practice for care planning and engagement of stroke and transient ischemic attack patients discharged home. Methods and Results We report on the first 871 patients enrolled in 20 North Carolina hospitals randomized to the intervention arm of COMPASS between July 2016 and February 2018; these patients completed a COMPASS follow-up visit within 14 days of hospital discharge. We also report user satisfaction results from 56 clinicians who used COMPASS-CP during these visits. COMPASS-CP identified more cognitive and depression deficits than physical deficits. Within 14-day posthospitalization, less than half of patients could list the major risk factors for stroke, 36% did not recognize blood pressure as a stroke risk factor, and 19% of patients were nonadherent with prescribed medications. Three-fourths of clinicians reported that COMPASS-CP identifies important factors impacting patients' recovery that they otherwise may have missed, and two-thirds were highly satisfied with COMPASS-CP. Conclusions The COMPASS-CP application meets an immediate need to incorporate PROs into the clinical workflow to develop patient-centered CP for stroke patients and has high user satisfaction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02588664.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.117.004444DOI Listing
August 2018

Changes in diabetes medication regimens and glycemic control in adolescents and young adults with youth-onset type 2 diabetes: The SEARCH for diabetes in youth study.

Pediatr Diabetes 2018 Sep 13;19(6):1065-1072. Epub 2018 Jun 13.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado.

Objective: The aim of this study was to describe recent medication patterns and changes in medication patterns and glycemic control in adolescents and young adults with incident type 2 diabetes (T2D).

Methods: Using data from the SEARCH for Diabetes in Youth Study, we conducted a cross-sectional analysis of treatments for adolescents and young adults with incident T2D in 2 periods (2002-2005 vs 2008/2012), and a longitudinal analysis of medications and glycemic control for a subset with baseline and follow-up visits. Comparisons were performed using χ , Fisher's exact, or ANOVA.

Results: Of 646 individuals in the cross-sectional analysis, a majority in each period received metformin (64.9% vs 70.4%) and/or insulin (38.1% vs 38.4%), while fewer used sulfonylureas (5.6% vs 3.6%) with non-significant changes over time. There was a significant reduction in thiazolidinedione use (5.0% vs 2.0%, P < .05). In the longitudinal analysis, 322 participants were followed for 7 years, on average. Baseline metformin users had a lower A1C (6.4% [46.7 mmol/mol]) compared to insulin (8.4% [68.2 mmol/mol], P < .001) or insulin plus any oral diabetes medication (ODM) users (7.7% [60.4 mmol/mol], P < .001). Among baseline metformin users (n = 138), 29.7% reported metformin at follow-up, with the remainder adding (19.6%) or switching to insulin (8.0%), ODM (15.9%), or lifestyle only (26.8%). Of those receiving insulin (±ODM) (n = 129), 76% reported insulin use at follow-up. Overall, 35% were at A1C goal (<7.0%, 53 mmol/mol) at follow-up.

Conclusions: Youth-onset T2D is still largely being treated with metformin and/or insulin. The majority treated were not at American Diabetes Association (ADA)-recommended goal 7 years after diagnosis.
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http://dx.doi.org/10.1111/pedi.12691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237662PMC
September 2018

Attempted salvage of infected cardiovascular implantable electronic devices: Are there clinical factors that predict success?

Pacing Clin Electrophysiol 2018 05 3;41(5):524-531. Epub 2018 Apr 3.

Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, CA, USA.

Background: Published guidelines mandate complete device removal in cases of cardiovascular implantable electronic device (CIED) infection. Clinical predictors of successful salvage of infected CIEDs have not been defined.

Methods: Data from the Multicenter Electrophysiologic Device Infection Collaboration, a prospective, observational, multinational cohort study of CIED infection, were used to investigate whether clinical predictors of successful salvage of infected devices could be identified.

Results: Of 433 adult patients with CIED infections, 306 (71%) underwent immediate device explantation. Medical management with device retention and antimicrobial therapy was initially attempted in 127 patients (29%). "Early failure" of attempted salvage occurred in 74 patients (58%) who subsequently underwent device explantation during the index hospitalization. The remaining 53 patients (42%) in the attempted salvage group retained their CIED. Twenty-six (49%) had resolution of CIED infection (successful salvage group) whereas 27 patients (51%) experienced "late" salvage failure. Upon comparing the salvage failure group, early and late (N = 101), to the group experiencing successful salvage of an infected CIED (N = 26), no clinical or laboratory predictors of successful salvage were identified. However, by univariate analysis, coagulase-negative staphylococci as infecting pathogens (P = 0.0439) and the presence of a lead vegetation (P = 0.024) were associated with overall failed salvage.

Conclusions: In patients with definite CIED infections, clinical and laboratory variables cannot predict successful device salvage. Until new data are forthcoming, device explantation should remain a mandatory and early management intervention in patients with CIED infection in keeping with existing expert guidelines unless medical contraindications exist or patients refuse device removal.
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http://dx.doi.org/10.1111/pace.13319DOI Listing
May 2018

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.

Circ Cardiovasc Genet 2017 Oct;10(5)

Background: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.

Methods And Results: Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (<5×10) for BP, of which 4 are new BP loci: rs9678851 (missense, ), rs7437940 (), rs13303 (missense, ), and rs1055144 (). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, ) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at ) was genome-wide significant.

Conclusions: We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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http://dx.doi.org/10.1161/CIRCGENETICS.117.001778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776077PMC
October 2017

Cumulative Number of Treatment Interventions Predicts Health-Related Quality of Life in Patients with Critical Limb Ischemia.

Ann Vasc Surg 2017 Oct 5;44:41-47. Epub 2017 May 5.

Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC; Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Health-related quality of life (QOL) is usually assessed after a defined interval following a single intervention, but critical limb ischemia (CLI) is a chronic condition where multiple interventions are often required over a patient's lifetime. We hypothesized that the impact of CLI treatment interventions on QOL is diminished in the setting of multiple previous interventions. To test this hypothesis, we performed a cross-sectional study evaluating associations between cumulative number of previous peripheral artery disease (PAD) treatment interventions and QOL adjusting for both comorbidity and disease severity.

Methods: Participants with CLI (abnormal ankle brachial index [ABI] plus rest pain and/or tissue loss) were enrolled in a cross-sectional study and completed a disease-specific QOL assessment, (the Vascular Quality of Life Questionnaire-6 [VascuQol-6]). Minimum ABI was used to assess disease severity, and comorbidity was evaluated based on Charlson Comorbidity Index. Cumulative number of PAD treatment interventions was defined based on the lifelong total for both legs. QOL associations were evaluated using a multivariable linear regression model adjusted for age and gender.

Results: Thirty-two patients with CLI participated. Mean age was 63 ± 10 years, 72% were men, and 63% were white; mean ABI was 0.6 ± 0.2. Mean VQ-6 score was 11.6 ± 4.2, and QOL was lower in patients with more previous interventions. Multivariable models demonstrated that an increasing number of previous treatment interventions negatively impacted QOL (P = 0.047), whereas positive associations were identified for female gender (P = 0.006) and ABI (P = 0.006). No association between comorbidity and QOL was identified.

Conclusions: Vascular-specific factors appear to be key determinants of QOL among patients with CLI, whereas comorbidity appears less important. Strategies focused on definitive and durable revascularization may reduce cumulative interventions and potentially maximize QOL for patients with CLI.
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http://dx.doi.org/10.1016/j.avsg.2017.01.029DOI Listing
October 2017

Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood.

JAMA 2017 02;317(8):825-835

Department of Pediatrics, University of Washington, Seattle.

Importance: The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown.

Objective: To determine the prevalence of and risk factors for complications related to type 1 diabetes vs type 2 diabetes among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence.

Design, Setting, And Participants: Observational study from 2002 to 2015 in 5 US locations, including 2018 participants with type 1 and type 2 diabetes diagnosed at younger than 20 years, with single outcome measures between 2011 and 2015.

Exposures: Type 1 and type 2 diabetes and established risk factors (hemoglobin A1c level, body mass index, waist-height ratio, and mean arterial blood pressure).

Main Outcomes And Measures: Diabetic kidney disease, retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension.

Results: Of 2018 participants, 1746 had type 1 diabetes (mean age, 17.9 years [SD, 4.1]; 1327 non-Hispanic white [76.0%]; 867 female patients [49.7%]), and 272 had type 2 (mean age, 22.1 years [SD, 3.5]; 72 non-Hispanic white [26.5%]; 181 female patients [66.5%]). Mean diabetes duration was 7.9 years (both groups). Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence of diabetic kidney disease (19.9% vs 5.8%; absolute difference [AD], 14.0%; 95% CI, 9.1%-19.9%; P < .001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; P = .02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; P < .001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; P < .001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; P < .001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, -3.1% to 6.5; P = .62). After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease (odds ratio [OR], 2.58; 95% CI, 1.39-4.81; P=.003), retinopathy (OR, 2.24; 95% CI, 1.11-4.50; P = .02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; P = .001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; P = .80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; P = .55).

Conclusions And Relevance: Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1, but frequent in both groups. These findings support early monitoring of youth with diabetes for development of complications.
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http://dx.doi.org/10.1001/jama.2017.0686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483855PMC
February 2017

Predictors of Dyslipidemia Over Time in Youth With Type 1 Diabetes: For the SEARCH for Diabetes in Youth Study.

Diabetes Care 2017 Apr 26;40(4):607-613. Epub 2017 Jan 26.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.

Objective: Understanding the risk factors associated with progression and regression of dyslipidemia in youth with type 1 diabetes may guide treatments.

Research Design And Methods: We studied 1,478 youth with type 1 diabetes (age 10.8 ± 3.9 years, 50% male, 77% non-Hispanic white, not on lipid-lowering medications) at baseline and at a mean follow-up of 7.1 ± 1.9 years in the SEARCH for Diabetes in Youth (SEARCH) study. Progression to dyslipidemia was defined as normal lipid concentrations at baseline and abnormal at follow-up (non-HDL-cholesterol [C] >130 mg/dL or HDL-C <35 mg/dL). Regression was defined as abnormal lipids at baseline and normal at follow-up. Multivariable logistic regression was used to evaluate factors associated with progression and regression compared with stable normal and stable abnormal, respectively. An area under the curve (AUC) variable was used for the time-varying covariates A1C and waist-to-height ratio (WHtR).

Results: Non-HDL-C progressed, regressed, was stable normal, and stable abnormal in 19%, 5%, 69%, and 7% of youth with type 1 diabetes, respectively. Corresponding percentages for HDL-C were 3%, 3%, 94%, and 1%, respectively. Factors associated with non-HDL-C progression were higher A1C AUC and higher WHtR AUC in males. Non-HDL-C regression was associated with lower WHtR AUC, and HDL-C progression was associated with male sex and higher WHtR AUC. HDL-C regression was not modeled due to small numbers.

Conclusions: A1C and WHtR are modifiable risk factors associated with change in dyslipidemia over time in youth with type 1 diabetes.
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http://dx.doi.org/10.2337/dc16-2193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360282PMC
April 2017

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

Nat Genet 2016 10 12;48(10):1162-70. Epub 2016 Sep 12.

Bill and Melinda Gates Foundation, Seattle, Washington, USA.

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
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http://dx.doi.org/10.1038/ng.3660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320952PMC
October 2016

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

J Med Genet 2016 12 1;53(12):835-845. Epub 2016 Sep 1.

Icelandic Heart Association, Kopavogur, Iceland.

Background: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.

Methods And Results: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.

Conclusions: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
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http://dx.doi.org/10.1136/jmedgenet-2016-103966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309131PMC
December 2016

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Nat Commun 2016 Jan 21;7:10023. Epub 2016 Jan 21.

Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, PO Box 30001, Groningen 9700 RB, The Netherlands.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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http://dx.doi.org/10.1038/ncomms10023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735748PMC
January 2016

Perceptions of Integrated Vascular Surgery Fellowship Graduates among Community Vascular Surgeons.

Ann Vasc Surg 2016 Jan 11;30:118-22.e1-2. Epub 2015 Nov 11.

Department of Vascular and Endovascular Surgery, Wake Forest University School of Medicine, Winston Salem, NC.

Background: Vascular training includes both integrated residency ("0+5") and postresidency fellowship ("5+2") programs. The impact of training models on attitudes toward graduates as prospective hires is incompletely understood, and existing studies have primarily surveyed surgeons from academic centers. We surveyed surgeons who were in active clinical practice but not affiliated with a medical school or training program to compare perceptions of integrated versus postgraduate programs.

Methods: Vascular surgeons not affiliated with a university-based practice were identified from membership rosters of one regional and one national specialty society and e-mailed an anonymous survey. The survey evaluated respondents' training, practice distribution, general surgery responsibilities, hiring practices, and perception of the integrated and postgraduate trained vascular surgeons. Agreement among specific responses was evaluated using McNemar's test.

Results: The survey was sent to 406 surgeons with 71 (17.5%) responding. A total of 42% of respondents indicated that half or more of their cases consisted of open procedures and 10% reported general surgery coverage as part of their practice. More respondents indicated that they consider postgraduate trained surgeons very mature (41% vs. 7%, P < 0.0001) and better prepared for open cases (89% vs. 28%, P < 0.0001), as well as endovascular cases (96% vs. 87%, P = 0.0339). Overall 84% stated that they would interview an integrated program graduate, although only 72% indicated that they would hire one. Overall 16.9% identified ability to cover general surgery as either very important or somewhat important characteristic for a potential hire.

Conclusions: Perceptions of 5+2 graduates as more mature and better prepared for opens surgical cases may influence hiring practices. This suggests that attitudes toward integrated versus 5+2 trained surgeons may differ between academic and community vascular surgeons. Further research is needed to assess whether these differences are related to actual differences in graduate skills, familiarity with integrated graduates, or other factors.
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http://dx.doi.org/10.1016/j.avsg.2015.10.006DOI Listing
January 2016

Exploring patient involvement in decision making for vascular procedures.

J Vasc Surg 2015 Oct 2;62(4):1032-1039.e2. Epub 2015 Jul 2.

Department of Vascular and Endovascular Surgery, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Developing patient-centered approaches to health care requires increased engagement of patients in their own care, including treatment decisions. Current levels of patient involvement in treatment choices have not been quantified, however, and whether patients desire greater decision-making responsibility is unknown. We conducted a prospective study to explore patients' desired vs experienced roles in treatment decisions, characterize perceptions of treatment outcomes, and identify important sources of information.

Methods: Patients undergoing elective vascular procedures completed a survey consisting of multiple choice, Likert scale, and open-ended questions. Statistics are displayed as mean ± standard deviation or count (%). Differences among procedure categories were evaluated using χ(2) or the Fisher exact test at P < .05 based on responses scored 1 to 2, indicating importance, agreement, or satisfaction based on a 1 to 5 Likert scale where 1 = "very important," "strongly agree" or "very satisfied".

Results: Of 101 patients who were contacted, 81 participated. Procedure categories included abdominal aortic aneurysm (AAA) repair in 20, arteriovenous (AV) hemodialysis access in 21, carotid endarterectomy (CEA) in 20, and intervention for lower extremity peripheral arterial disease (PAD) in 20. Participants preferred discussion of all treatments being considered vs only the provider's recommended treatment (90% vs 56%) and choosing together with the provider vs having the provider choose for them (93% vs 62%). Although participants indicated adequate information to ask questions without feeling overwhelmed, only 77% agreed that they had the opportunity to ask questions and only 54% indicated that they were offered a choice. Thirty-seven participants (46%) considered their first treatment was successful, 38% considered a subsequent treatment was successful, and 16% considered none of their treatments were successful. Participants undergoing PAD and AV access procedures most often felt confused or overwhelmed (25% and 24%, respectively, vs 0% for AAA and CEA; P < .01). Patients with PAD had adequate information least often (70% vs 85% for AAA, 100% for AV access, and 95% for CEA; P = .01), had the lowest satisfaction with understanding of their diagnosis (65% vs 95% for AAA, 100% for AV access, and 95% for CEA; P < .01), and most often considered none of their treatments successful (35% vs 0% for AAA, 15% for AV access, and 15% for CEA; P = .02). Providers were identified as the most important information source.

Conclusions: Patients have variable levels of participation in decision making related to vascular procedures and often consider their treatments unsuccessful. Although providers are important sources of information, patients still prefer to discuss all options being considered and contribute to shared decision making.
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http://dx.doi.org/10.1016/j.jvs.2015.04.443DOI Listing
October 2015

Association of parental history of diabetes with cardiovascular disease risk factors in children with type 2 diabetes.

J Diabetes Complications 2015 May-Jun;29(4):534-9. Epub 2015 Feb 10.

Department of Pediatrics and Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Aims: Determine if parental diabetes (DM) is associated with unhealthier cardiovascular disease (CVD) risk profiles in youth with type 2 diabetes (T2D), and whether associations differed by race/ethnicity.

Methods: Family history was available for 382 youth with T2D from 2001 prevalent and 2002-2005 incident SEARCH for Diabetes in Youth cohorts. Parental DM was evaluated in two ways: two-category-any parent vs. no parent DM (evaluated overall and stratified by race/ethnicity); and four-category-both parents, mother only, father only, or no parent DM (evaluated overall only). Associations with hemoglobin A1c (HbA1c), fasting lipids, blood pressure (BP), and urine albumin:creatinine ratio (ACR) were examined using regression models.

Results: Overall, sample characteristics included: 35.9% male, 19.1% non-Hispanic white (NHW), mean T2D duration 26.6±22.2months, mean HbA1c 7.9%±2.5% (62.6±27.8mmol/mol). Unadjusted two-category comparisons showed that youth with parental DM had higher HbA1c, higher DBP, and higher frequency of elevated ACR. Adjusted two-category comparisons showed associations remaining in non-stratified analysis for ACR [OR (95% CI)=2.3 (1.1, 5.0)] and in NHW youth for HbA1c [6.8%±0.4 vs. 8.0±0.4 (51.1±4.8 vs. 63.9±4.2mmol/mol), p=.015], DBP (67.7%±4.5 vs. 76.9±4.4mm Hg, p=.014) and lnTG (4.7±0.3 vs. 5.3±0.3, p=.008). There were no significant findings in the adjusted four-category evaluation.

Conclusions: Parental history of diabetes may be associated with unhealthier CVD risk factors in youth with T2D.
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http://dx.doi.org/10.1016/j.jdiacomp.2015.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414789PMC
April 2016

Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.

PLoS One 2014 26;9(12):e113203. Epub 2014 Dec 26.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.

Methods And Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1 × 10(-8)), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.

Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113203PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277270PMC
August 2015

Genome-wide association study of kidney function decline in individuals of European descent.

Kidney Int 2015 May 10;87(5):1017-29. Epub 2014 Dec 10.

Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.
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http://dx.doi.org/10.1038/ki.2014.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425568PMC
May 2015

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

Nat Commun 2014 Oct 28;5:5068. Epub 2014 Oct 28.

International Centre for Circulatory Health, Imperial College, London SW7 2AZ, UK.

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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http://dx.doi.org/10.1038/ncomms6068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220464PMC
October 2014

Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes.

Pediatr Diabetes 2015 Jun 7;16(4):280-6. Epub 2014 Aug 7.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D.

Study Design: We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c).

Results: We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz.

Conclusions: Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D.
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http://dx.doi.org/10.1111/pedi.12162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320680PMC
June 2015
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