Faculty Bibliography
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Demographic Correlates of Short-Term Mortality Among Youth and Young Adults With Youth-Onset Diabetes Diagnosed From 2002 to 2015: The SEARCH for Diabetes in Youth Study
OBJECTIVE:To examine short-term mortality and cause of death among youth and young adults (YYAs) with youth-onset diabetes. RESEARCH DESIGN AND METHODS:We included 19,717 YYAs newly diagnosed with diabetes before 20 years of age from 1 January 2002 to 31 December 2015 enrolled in the SEARCH for Diabetes in Youth Study. Of these, 14,721 had type 1; 4,141 type 2; and 551 secondary and 304 other/unknown diabetes type. Cases were linked with the National Death Index through 31 December 2017. We calculated standardized mortality ratios (SMRs) and 95% CIs based on age, sex, and race/ethnicity for state and county population areas and examined underlying causes of death. RESULTS:< 0.001). SMRs were significantly higher for individuals with type 1 diabetes who were <20 years of age, non-Hispanic White and Hispanic, and female and for individuals with type 2 diabetes who were <25 years of age, from all race/ethnic minority groups, and from both sexes. CONCLUSIONS:Excess mortality was observed among YYAs for each type of diabetes with differences in risk associated with diabetes type, age, race/ethnicity, and sex. The root causes of excess mortality among YYAs with diabetes merit further study.
PMCID:8669529
PMID: 34607833
ISSN: 1935-5548
CID: 5220822
Journal of the American Medical Directors Association. 2021:22(12):2500-2503.DOI: 10.1016/j.jamda.2021.09.019
Absence of COVID-19 Disease Among Chronically Ventilated Nursing Home Patients
OBJECTIVE:To describe the experience of COVID-19 disease among chronically ventilated and nonventilated nursing home patients living in 3 separate nursing homes. DESIGN:Observational study of death, respiratory illness and COVID-19 polymerase chain reaction (PCR) results among residents and staff during nursing home outbreaks in 2020. SETTING AND PARTICIPANTS:93 chronically ventilated nursing home patients and 1151 nonventilated patients living among 3 separate nursing homes on Long Island, New York, as of March 15, 2020. Illness, PCR results, and antibody studies among staff are also reported. MEASUREMENTS:Data were collected on death rate among chronically ventilated and nonventilated patients between March 15 and May 15, 2020, compared to the same time in 2019; prevalence of PCR positivity among ventilated and nonventilated patients in 2020; reported illness, PCR positivity, and antibody among staff. RESULTS:Total numbers of deaths among chronically ventilated nursing home patients during this time frame were similar to the analogous period 1 year earlier (9 of 93 in 2020 vs 8 of 100 in 2019, P = .8), whereas deaths among nonventilated patients were greatly increased (214 of 1151 in 2020 vs 55 of 1189 in 2019, P < .001). No ventilated patient deaths were clinically judged to be COVID-19 related. No clusters of COVID-19 illness could be demonstrated among ventilated patients. Surveillance PCR testing of ventilator patients failed to reveal COVID-19 positivity (none of 84 ventilator patients vs 81 of 971 nonventilator patients, P < .002). Illness and evidence of COVID-19 infection was demonstrated among staff working both in nonventilator and in ventilator units. CONCLUSIONS AND IMPLICATIONS:COVID-19 infection resulted in illness and death among nonventilated nursing home residents as well as among staff. This was not observed among chronically ventilated patients. The mechanics of chronic ventilation appears to protect chronically ventilated patients from COVID-19 disease.
PMCID:8479505
PMID: 34648760
ISSN: 1538-9375
CID: 5065292
Determining diagnosis date of diabetes using structured electronic health record (EHR) data: the SEARCH for diabetes in youth study
BACKGROUND:Disease surveillance of diabetes among youth has relied mainly upon manual chart review. However, increasingly available structured electronic health record (EHR) data have been shown to yield accurate determinations of diabetes status and type. Validated algorithms to determine date of diabetes diagnosis are lacking. The objective of this work is to validate two EHR-based algorithms to determine date of diagnosis of diabetes. METHODS:A rule-based ICD-10 algorithm identified youth with diabetes from structured EHR data over the period of 2009 through 2017 within three children's hospitals that participate in the SEARCH for Diabetes in Youth Study: Cincinnati Children's Hospital, Cincinnati, OH, Seattle Children's Hospital, Seattle, WA, and Children's Hospital Colorado, Denver, CO. Previous research and a multidisciplinary team informed the creation of two algorithms based upon structured EHR data to determine date of diagnosis among diabetes cases. An ICD-code algorithm was defined by the year of occurrence of a second ICD-9 or ICD-10 diabetes code. A multiple-criteria algorithm consisted of the year of first occurrence of any of the following: diabetes-related ICD code, elevated glucose, elevated HbA1c, or diabetes medication. We assessed algorithm performance by percent agreement with a gold standard date of diagnosis determined by chart review. RESULTS:Among 3777 cases, both algorithms demonstrated high agreement with true diagnosis year and differed in classification (p = 0.006): 86.5% agreement for the ICD code algorithm and 85.9% agreement for the multiple-criteria algorithm. Agreement was high for both type 1 and type 2 cases for the ICD code algorithm. Performance improved over time. CONCLUSIONS:Year of occurrence of the second ICD diabetes-related code in the EHR yields an accurate diagnosis date within these pediatric hospital systems. This may lead to increased efficiency and sustainability of surveillance methods for incidence of diabetes among youth.
PMCID:8502379
PMID: 34629073
ISSN: 1471-2288
CID: 5038732
Association of anti-phospholipid antibodies (APL) with poor clinical outcomes in hospitalized patients with COVID-19 [Meeting Abstract]
Background/Purpose: Critically ill patients with COVID-19 infection have a profound hypercoagulable state and can often develop thromboses in many different vascular beds. Given the presence of anti-phospholipid antibodies among COVID-19 patients reported previously, we hypothesized that poor outcomes and thrombosis could also be promoted by autoimmunity. In this retrospective case control analysis, we aimed to evaluate associations between aPL titers, clinical outcomes and mortality in hospitalized patients admitted with COVID-19 infection.
Method(s): We analyzed 138 electronic medical records of patients who were admitted to NYU Langone Hospital -Long Island between the months of March-April 2020 with findings of COVID-19 positivity via PCR and who had aPL titers determined. Patients with elevated titers of beta-2-Glycoprotein IgG, IgM, IgA and/or cardiolipin IgG, IgM, IgA were compared to those who were not elevated. Patients with positive lupus anticoagulant titers only were excluded due to prevalent use of anti-coagulation during this time. COVID-19 positive patients with aPL titers were assessed for clinical events (including DVT, PE, MI, CVA, extremity ischemia, skin ulcerations, visceral thrombosis and ocular and line occlusions) and mortality. The control group included patients that were negative for aPL antibody titers. Associations between Anti-Phospholipid (aPL) titer positivity and clinical events was assessed by Chi-square analysis using Fisher's exact test.
Result(s): The predominant aPL species that was noted in COVID-19 patients was anti-cardiolipin IgM. Of those patients with elevated antibody titers, cardiolipin IgM, IgG, IgA, and beta2GPI antibodies were prevalent at rates of 98.9%, 26.7%, 19.2%, and 16.5%, respectively. Multiple aPL isotypes were detected in several patients. There was a positive association between aPL positivity and elevations in IL-6, CRP, D-dimer, and LDH (P< 0.05). There was an increased incidence of clinical events in patients with COVID-19 and positive aPL titers (52/83 or 62%) compared to those who were aPL negative (32/55 or 58% ), however this association was not statistically significant. No significant association was detected between positive aPL titers and gender, age, or self-identified ethnicity. An increased incidence of ARDS and a rising serum creatinine was noted in the aPL positive group (P = 0.03 and P= 0.05 respectively). A significant increase in mortality was identified for the aPL positive group (P=0.01).
Conclusion(s): These findings suggest that aPL titers may provide insight into disease prognosis and outcome in hospitalized patients with COVID-19. Despite lack of significant association with discrete thrombotic events, association of aPL positivity with rising serum creatinine and ARDS suggest that aPL may contribute to end organ dysfunction through enhanced microthrombosis, resulting in increased mortality. (Figure Presented)
Method(s): We analyzed 138 electronic medical records of patients who were admitted to NYU Langone Hospital -Long Island between the months of March-April 2020 with findings of COVID-19 positivity via PCR and who had aPL titers determined. Patients with elevated titers of beta-2-Glycoprotein IgG, IgM, IgA and/or cardiolipin IgG, IgM, IgA were compared to those who were not elevated. Patients with positive lupus anticoagulant titers only were excluded due to prevalent use of anti-coagulation during this time. COVID-19 positive patients with aPL titers were assessed for clinical events (including DVT, PE, MI, CVA, extremity ischemia, skin ulcerations, visceral thrombosis and ocular and line occlusions) and mortality. The control group included patients that were negative for aPL antibody titers. Associations between Anti-Phospholipid (aPL) titer positivity and clinical events was assessed by Chi-square analysis using Fisher's exact test.
Result(s): The predominant aPL species that was noted in COVID-19 patients was anti-cardiolipin IgM. Of those patients with elevated antibody titers, cardiolipin IgM, IgG, IgA, and beta2GPI antibodies were prevalent at rates of 98.9%, 26.7%, 19.2%, and 16.5%, respectively. Multiple aPL isotypes were detected in several patients. There was a positive association between aPL positivity and elevations in IL-6, CRP, D-dimer, and LDH (P< 0.05). There was an increased incidence of clinical events in patients with COVID-19 and positive aPL titers (52/83 or 62%) compared to those who were aPL negative (32/55 or 58% ), however this association was not statistically significant. No significant association was detected between positive aPL titers and gender, age, or self-identified ethnicity. An increased incidence of ARDS and a rising serum creatinine was noted in the aPL positive group (P = 0.03 and P= 0.05 respectively). A significant increase in mortality was identified for the aPL positive group (P=0.01).
Conclusion(s): These findings suggest that aPL titers may provide insight into disease prognosis and outcome in hospitalized patients with COVID-19. Despite lack of significant association with discrete thrombotic events, association of aPL positivity with rising serum creatinine and ARDS suggest that aPL may contribute to end organ dysfunction through enhanced microthrombosis, resulting in increased mortality. (Figure Presented)
PMCID:
EMBASE:637274568
ISSN: 2326-5205
CID: 5164742
Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017
Importance:Changes in the prevalence of youth-onset diabetes have previously been observed. Objective:To estimate changes in prevalence of type 1 and type 2 diabetes in youths in the US from 2001 to 2017. Design, Setting, and Participants:In this cross-sectional observational study, individuals younger than 20 years with physician-diagnosed diabetes were enumerated from 6 areas in the US (4 geographic areas, 1 health plan, and select American Indian reservations) for 2001, 2009, and 2017. Exposures:Calendar year. Main Outcomes and Measures:Estimated prevalence of physician-diagnosed type 1 and type 2 diabetes overall and by race and ethnicity, age, and sex. Results:Among youths 19 years or younger, 4958 of 3.35 million had type 1 diabetes in 2001, 6672 of 3.46 million had type 1 diabetes in 2009, and 7759 of 3.61 million had type 1 diabetes in 2017; among those aged 10 to 19 years, 588 of 1.73 million had type 2 diabetes in 2001, 814 of 1.85 million had type 2 diabetes in 2009, and 1230 of 1.85 million had type 2 diabetes in 2017. The estimated type 1 diabetes prevalence per 1000 youths for those 19 years or younger increased significantly from 1.48 (95% CI, 1.44-1.52) in 2001 to 1.93 (95% CI, 1.88-1.98) in 2009 to 2.15 (95% CI, 2.10-2.20) in 2017, an absolute increase of 0.67 per 1000 youths (95%, CI, 0.64-0.70) and a 45.1% (95% CI, 40.0%-50.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic White (0.93 per 1000 youths [95% CI, 0.88-0.98]) and non-Hispanic Black (0.89 per 1000 youths [95% CI, 0.88-0.98]) youths. The estimated type 2 diabetes prevalence per 1000 youths aged 10 to 19 years increased significantly from 0.34 (95% CI, 0.31-0.37) in 2001 to 0.46 (95% CI, 0.43-0.49) in 2009 to 0.67 (95% CI, 0.63-0.70) in 2017, an absolute increase of 0.32 per 1000 youths (95% CI, 0.30-0.35) and a 95.3% (95% CI, 77.0%-115.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic Black (0.85 per 1000 youths [95% CI, 0.74-0.97]) and Hispanic (0.57 per 1000 youths [95% CI, 0.51-0.64]) youths. Conclusions and Relevance:In 6 areas of the US from 2001 to 2017, the estimated prevalence of diabetes among children and adolescents increased for both type 1 and type 2 diabetes.
PMCID:8385600
PMID: 34427600
ISSN: 1538-3598
CID: 5011072
Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration
OBJECTIVE:Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS/METHODS:We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS:= 0.006). CONCLUSIONS:= 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.
PMID: 34362814
ISSN: 1935-5548
CID: 4988762
Genetic landscape of Gullah African Americans
OBJECTIVES/OBJECTIVE:Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. MATERIALS AND METHODS/METHODS:We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture. RESULTS:Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. DISCUSSION/CONCLUSIONS:This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.
PMID: 34008864
ISSN: 1096-8644
CID: 4877172
Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes
We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide-significant (P < 5 × 10-8) regions, including 36 that are new. We define credible sets of T1D-associated variants and show that they are enriched in immune-cell accessible chromatin, particularly CD4+ effector T cells. Using chromatin-accessibility profiling of CD4+ T cells from 115 individuals, we map chromatin-accessibility quantitative trait loci and identify five regions where T1D risk variants co-localize with chromatin-accessibility quantitative trait loci. We highlight rs72928038 in BACH2 as a candidate causal T1D variant leading to decreased enhancer accessibility and BACH2 expression in T cells. Finally, we prioritize potential drug targets by integrating genetic evidence, functional genomic maps and immune protein-protein interactions, identifying 12 genes implicated in T1D that have been targeted in clinical trials for autoimmune diseases. These findings provide an expanded genomic landscape for T1D.
PMID: 34127860
ISSN: 1546-1718
CID: 4911522
Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk
BACKGROUND:Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES/OBJECTIVE:The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS:A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS:= 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE/UNASSIGNED:Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
PMID: 34180274
ISSN: 1542-6270
CID: 4926192
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
PMID: 32372009
ISSN: 1476-5578
CID: 4430172
