Faculty Bibliography

BACKGROUND:-associated nephropathy currently exists. METHODS:-associated nephropathy in a future when treatment is available. A systematic literature search of the MEDLINE and Embase databases was conducted to identify relevant evidence published from January 1, 2009 to July 14, 2020. RESULTS:-associated nephropathy and on features of a successful education program to raise awareness among the patient community. The group also highlighted the unmet need for a specific treatment and agreed on best practice for management of these patients should a treatment become available. CONCLUSIONS:-associated nephropathy.

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P=3.2×10^-8, odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P=8.0×10^-20, OR 1.58), rs72982988 near MC4R (P=4.4×10^-14, OR=1.53), rs200893788 in CDC123 (P=1.1×10^-12, OR= 1.32), rs2237892 in KCNQ1 (P=4.8×10^-11, OR=1.59), rs937589119 in IGF2BP2 (P=3.1×10^-9, OR=1.34) and rs113748381 in SLC16A11 (P=4.1×10^-8, OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in CPEB2 (P=3.2×10^-8, OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

The purpose of this study was to examine factors that influence a person's choice of cognitive-behavioral therapy (CBT) or yoga, the stability of these preferences, and the impact of preference on engagement and process measures. We conducted a randomized preference trial of CBT and yoga in 500 adults ≥60 years with symptoms of worry. Participants reported their intervention preference, strength of preference, and factors impacting preference. Engagement in the intervention (session completion and dropout rates) was assessed. Process measures included satisfaction with the intervention, therapeutic alliance, and intervention expectancy. Neither intervention preference (48% and 52% chose CBT and yoga, respectively) nor strength of preference differed significantly between the two preference trial groups. Intervention expectancies at baseline among those in the preference trial were approximately 4.5 units (40-point scale) higher for their preferred intervention (p < .0001 within each group). A principal component analysis of factors influencing preference identified three constructs. Using logistic regression, components focused on attitudes about CBT or yoga were predictive of ultimate preference (odds ratio = 11.5, 95% C.I.6.3-21.0 per 1SD difference in component 1 for choosing CBT; odds ratio = 7.8, 95% CI4.3-13.9 per 1SD difference in component 2 for choosing yoga). There were no significant differences between the randomized and preference trials on intervention adherence, completion of assessments, intervention satisfaction, or working alliance. Receiving a preferred treatment had no significant effects on intervention outcomes through participant engagement or process measures. When options are limited, providers may have confidence in offering the most readily available non-pharmacological treatments.

Background/UNASSIGNED:Patients on maintenance hemodialysis are particularly vulnerable to infection and hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to immunocompromised patients and the clustering that occurs in outpatient dialysis units, the seroprevalence of COVID-19 antibodies in this population is unknown and has significant implications for public health. Also, little is known about their risk factors for hospitalization. Methods/UNASSIGNED:nasopharyngeal, real-time, reverse-transcriptase PCR (RT-PCR); SARS-CoV-2 IgG seropositivity; hospitalization; and mortality. Results/UNASSIGNED:<0.001) compared with those who tested negative. Higher positivity rates were also observed among those who took taxis and ambulettes to and from dialysis, compared with those who used personal transportation. Antibodies were detected in all of the patients with a positive PCR result who underwent serologic testing. Of those that were seropositive, 32% were asymptomatic. The hospitalization rate on the basis of either antibody or PCR positivity was 35%, with a hospital mortality rate of 33%. Aside from COPD, no other variables were more prevalent in patients who were hospitalized. Conclusions/UNASSIGNED:We observed significant differences in rates of COVID-19 infection within three outpatient dialysis units, with universal seroconversion. Among patients with ESKD, rates of asymptomatic infection appear to be high, as do hospitalization and mortality rates.

OBJECTIVE:high-risk genotypes and kidney outcomes, organ damage accrual and death in 100 Ghanaian patients with SLE. METHODS:This was a prospective cohort study of 100 SLE outpatients who sought care at Korle bu Teaching Hospital in Accra, Ghana. Adult patients who met 4 American College of Rheumatology criteria for SLE were genotyped for APOL1 and followed longitudinally for SLE activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) hybrid and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Outcomes of interest were kidney function, SDI and case fatality. RESULTS:high-risk genotype (2RV) associated with end-stage renal disease (ESRD) at an OR of 14 (p=0.008). These patients accrued more SDI points particularly in renal and neurological domains. The SDI was 81.3% higher in 2RV patients compared with 0RV or 1RV patients despite no difference in SLE activity (p=0.01). After a 12-month period of observation, 3/12 (25%) of the 2RV patients died compared with 2/88 (2.3%) of the 0RV or 1RV carriers (OR=13.6, p=0.01). Deaths were due to end-stage kidney disease and heart failure. CONCLUSION/CONCLUSIONS:high-risk patients exhibited progressive renal disease, organ damage accrual and a 13-fold higher case fatality.

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

BACKGROUND:Although surveillance for diabetes in youth relies on provider-assigned diabetes type from medical records, its accuracy compared to an etiologic definition is unknown. METHODS:Using the SEARCH for Diabetes in Youth Registry, we evaluated the validity and accuracy of provider-assigned diabetes type abstracted from medical records against etiologic criteria that included the presence of diabetes autoantibodies (DAA) and insulin sensitivity. Youth who were incident for diabetes in 2002-06, 2008, or 2012 and had complete data on key analysis variables were included (n=4,001, 85% provider diagnosed type 1). The etiologic definition for type 1 diabetes was ≥1 positive DAA titer(s) or negative DAA titers in the presence of insulin sensitivity and for type 2 diabetes was negative DAA titers in the presence of insulin resistance. RESULTS:Provider diagnosed diabetes type correctly agreed with the etiologic definition of type for 89.9% of cases. Provider diagnosed type 1 diabetes was 96.9% sensitive, 82.8% specific, had a positive predictive value (PPV) of 97.0% and a negative predictive value (NPV) of 82.7%. Provider diagnosed type 2 diabetes was 82.8% sensitive, 96.9% specific, had a PPV and NPV of 82.7% and 97.0%, respectively. CONCLUSION/CONCLUSIONS:Provider diagnosis of diabetes type agreed with etiologic criteria for 90% of the cases. While the sensitivity and PPV were high for youth with type 1 diabetes, the lower sensitivity and PPV for type 2 diabetes highlights the value of DAA testing and assessment of insulin sensitivity status to ensure estimates are not biased by misclassification. This article is protected by copyright. All rights reserved.

BACKGROUND:The purpose of this study was to compare the effects of cognitive-behavioral therapy (CBT) and yoga on late-life worry, anxiety, and sleep; and examine preference and selection effects on these outcomes. METHODS:A randomized preference trial of CBT and yoga was conducted in community-dwelling adults 60 years or older, who scored 26 or above on the Penn State Worry Questionnaire-Abbreviated (PSWQ-A). CBT consisted of 10 weekly telephone sessions. Yoga consisted of 20 biweekly group yoga classes. The primary outcome was worry (PSWQ-A); the secondary outcomes were anxiety (PROMIS-Anxiety) and sleep (Insomnia Severity Index [ISI]). We examined both preference effects (average effect for those who received their preferred intervention [regardless of whether it was CBT or yoga] minus the average for those who did not receive their preferred intervention [regardless of the intervention]) and selection effect (which addresses the question of whether there is a benefit to getting to select one intervention over the other, and measures the effect on outcomes of self-selection to a specific intervention). RESULTS:Five hundred older adults were randomized to the randomized trial (125 each in CBT and yoga) or the preference trial (120 chose CBT; 130 chose yoga). In the randomized trial, the intervention effect of yoga compared with CBT adjusted for baseline psychotropic medication use, gender, and race was 1.6 (-0.2, 3.3), p = .08 for the PSWQ-A. Similar results were observed with PROMIS-Anxiety (adjusted intervention effect: 0.3 [-1.5, 2.2], p = .71). Participants randomized to CBT experienced a greater reduction in the ISI compared with yoga (adjusted intervention effect: 2.4 [1.2, 3.7], p < .01]). Estimated in the combined data set (N = 500), the preference and selection effects were not significant for the PSWQ-A, PROMIS-Anxiety, and ISI. Of the 52 adverse events, only two were possibly related to the intervention. None of the 26 serious adverse events were related to the study interventions. CONCLUSIONS:CBT and yoga were both effective at reducing late-life worry and anxiety. However, a greater impact was seen for CBT compared with yoga for improving sleep. Neither preference nor selection effects was found.

BACKGROUND:Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES/OBJECTIVE:To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS:A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS:Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (β (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS:In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.