Publications by authors named "Melissa Tracy"

106 Publications

Pearls and Purple: The Dawn of a Modern Age.

J Am Heart Assoc 2021 Feb 23;10(5):e020903. Epub 2021 Feb 23.

From the Division of Cardiology Rush Heart Center for Women Rush University Medical Center Chicago IL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.121.020903DOI Listing
February 2021

The Impact of Seasonal Changes on Thyroxine and Thyroid-Stimulating Hormone in Newborns.

Int J Neonatal Screen 2021 Feb 3;7(1). Epub 2021 Feb 3.

Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, NY 12208, USA.

Newborn screening for congenital hypothyroidism (CH) is performed by measuring the concentration of thyroxine (T4) and/or thyroid-stimulating hormone (TSH) in dried blood spots. Unfortunately, the levels of T4 and TSH vary due to multiple factors, and therefore the false-positive rate for the test is a challenge. We analyzed screening data from 2008 to 2017 to determine the effect of seasonal changes and manufacturer kit lot changes on T4 and TSH values and on numbers of infants referred. Over a 10-year period, we screened 2.4 million infants using commercially available fluoroimmunoassays to measure T4 and TSH concentrations in dried blood spots. During colder months, daily mean T4 and TSH values were higher and referral rates and false-positive rates were higher. However, there was no significant difference between the number of confirmed CH cases. Furthermore, in rare instances, we observed differences in T4 daily mean values during the 10-year period when manufacturer kit lot changes were made. Seasonal temperature variations influence measured T4 and TSH values and consequently lower the positive predictive value for CH testing in colder months. Newborn screening (NBS) programs should be aware that manufacturer kit lot changes may also influence T4 values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijns7010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930942PMC
February 2021

A Case of Asymptomatic Pulmonary Artery Aneurysm with Review of Management Strategies.

Case Rep Cardiol 2020 14;2020:8885260. Epub 2020 Oct 14.

Division of Cardiovascular Medicine, RUSH University Medical Center, Chicago IL, USA.

Pulmonary artery aneurysm (PAA) is defined as pulmonary artery diameter greater than 4 cm. With advances in cardiac imaging, the detection rate has increased but the natural history remains unknown. We present the case of a large, incidentally identified PAA in a patient with a history of congenital pulmonic stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8885260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582066PMC
October 2020

Knowledge and attitudes towards ambulatory treatment of tuberculоsis in Kazakhstan.

BMC Health Serv Res 2020 Jun 22;20(1):563. Epub 2020 Jun 22.

Columbia University School of Social Work, 1255 Amsterdam Avenue, New York, NY, USA.

Background: Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes.

Methods: New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012-2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment.

Results: The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members.

Conclusions: This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-020-05413-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310255PMC
June 2020

The relationship between parental involvement in childhood and depression in early adulthood.

J Affect Disord 2020 08 3;273:173-182. Epub 2020 May 3.

Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, One University Place, Rensselaer 12144-3456, NY, United States. Electronic address:

Background: Positive early life experiences may help prevent depression later in life. We examined the accumulated benefit, timing, and trajectories of positive parental involvement in childhood in association with incident depression in early adulthood.

Methods: Prospectively assessed Avon Longitudinal Study of Parents and Children (ALSPAC) data (n = 7120) were analyzed. Overall and developmental stage-specific parental involvement scores were estimated from multiple measures from birth to age 7 years. Trajectory groups of parental involvement were derived via latent class growth analysis. At 18 years, depression cases were identified with diagnostic instruments. Multiple imputation was used to handle missingness. We constructed logistic regression models with potential confounders adjusted.

Results: Participants from trajectory groups with higher average parenting scores over time had 30% to 40% lower odds of developing depression in early adulthood than participants from the group with the lowest average parenting score over time. However, the relationship became non-significant when all covariates were adjusted. A one-unit increase in the overall parenting score corresponded to 12% lower odds of developing depression (adjusted OR=0.88 [0.79-0.98]). Protective effects on incident depression in early adulthood from parental involvement in school age (5-7 years), and not at other ages, were observed (OR=0.87 [0.77-0.99] for a one-unit increase in the parenting score at school age). However, the relationship became non-significant when all covariates were adjusted (OR=0.91 [0.80-1.03]).

Limitations: Measurements of parental involvement were only based on maternal report. The study has limited generalizability to other racial/ethnic groups.

Conclusion: Higher level of parental involvement during childhood lowers the risk of developing depression in early adulthood. These results suggest positive early life experiences may promote mental health across the life course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.03.108DOI Listing
August 2020

Erratum: Creation of the Person-Centered Wellness Home in Older Adults.

Innov Aging 2020;4(1):igaa005. Epub 2020 Mar 18.

Northeast Center for Occupational Health and Safety, Bassett Healthcare Network, Cooperstown, New York.

[This corrects the article DOI: 10.1093/geroni/igz055.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geroni/igaa005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078850PMC
March 2020

Influence of breast reconstruction on technical aspects of echocardiographic image acquisition compared with physician-assessed image quality.

Cardiooncology 2019 4;5:17. Epub 2019 Nov 4.

5Division of Cardiology, Rush University Medical Center, 1717 West Congress Parkway, Kellogg Bldg, Suite 328, Chicago, IL 60612 USA.

Introduction: Assessment of cardiac function after treatment for breast cancer relies on interval evaluation of ventricular function through echocardiography. Women who undergo mastectomy more frequently choose to undergo breast reconstruction with implant. This could impede assessment of cardiac function in those with left-sided implant. We aimed to examine whether left-sided breast reconstruction with tissue expanders (TE) affect echo image acquisition and quality, possibly affecting clinical decision-making.

Methods: A retrospective case-control study was conducted in 190 female breast cancer patients who had undergone breast reconstruction with TE at an urban academic center. Echocardiographic technical assessment and image quality were respectively classified as excellent/good or adequate/technically difficult by technicians; and excellent/good or adequate/poor by 2 board-certified cardiologist readers. Likelihood ratio was used to test multivariate associations between image quality and left-sided TE.

Results: We identified 32 women (81.3% white; mean age 48 years) with left-sided/bilateral TE, and 158 right-sided/no TE (76.6% white, mean age 57 years). In multivariable analyses, we found a statistically significant difference in technician-assessed difficulty in image acquisition between cases and controls ( = 0.01); but no differences in physician-assessed image quality between cases and controls ( = 0.09, Pearson's r = 0.467).

Conclusions: Left-sided breast TE appears to affect the technical difficulty of echo image acquisition, but not physician-assessed echo image quality. This likely means that echo technicians absorb most of the impediments associated with imaging patients with breast TE such that the presence of TE has no bearing on downstream clinical decision-making associated with echo image quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40959-019-0052-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048107PMC
November 2019

The relationship between inflammatory dietary pattern in childhood and depression in early adulthood.

Brain Behav Immun Health 2020 Feb;2:100017

Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, 1 University Place, Rensselaer, NY 12144, United States.

Background: Inflammation may be a hidden process in the relationship between dietary intake and depression, but no study has evaluated the role of diet and inflammation jointly in explaining depression risk in early life. The current study aims to investigate the relationship between inflammatory dietary pattern (IDP) in childhood and depression in early adulthood.

Methods: This study used data prospectively collected over 10 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n ​= ​6939) free from depression at baseline (age 8.5 years). An IDP score was empirically derived via reduced rank regression and stepwise linear regression based on dietary intake data from the food frequency questionnaire at 8.5 years and levels of inflammatory biomarkers, C-reactive protein and interleukin-6, at 9.5 years. At age 18 years, depression cases were identified via the International Statistical Classification of Diseases, 10th Revision (ICD-10) diagnosis and the Clinical Interview Schedule-Revised (CIS-R) depression score. Logistic regression models were constructed to examine the relationship between the IDP score and risk of depression adjusted for potential confounders. Analyses stratified by weight status were also conducted. Multiple imputations were utilized to minimize bias due to loss-to-follow-up.

Results: Participants in the highest tertile of IDP score had 1.34 times odds to develop depression compared to those in the lowest tertile (95% CI, 1.08-1.66; -trend<0.01), after dietary misreporting status and energy intake were adjusted. After all covariates were adjusted, the relationship between IDP tertiles and depression was attenuated (highest tertile vs. lowest tertile: OR ​= ​1.21; 95% CI, 0.96-1.51); in addition, the relationship was marginally significant among participants who were not overweight or obese (p ​< ​0.10) but not significant among participants who were overweight or obese.

Conclusions: Higher IDP in childhood seems to be associated with higher depression risk in early adulthood. The study provides preliminary evidence that chronic inflammation may underlie the relationship between diet and depression even for children, especially those who are not overweight or obese.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbih.2019.100017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043331PMC
February 2020

Creation of the Person-Centered Wellness Home in Older Adults.

Innov Aging 2020 22;4(2):igz055. Epub 2020 Jan 22.

Northeast Center for Occupational Health and Safety, Bassett Healthcare Network, Cooperstown, New York.

Background And Objectives: Extending the Patient-Centered Medical Home (PCMH) model into the community may address the poor linkage between medical clinics and underserved communities. Our first of three objectives was to determine if peer leaders and wellness coaches can be the relationship center of wellness care. We evaluated the Self-management Resource Center Small Group Programs (SMRCSGP), plus wellness coaching, as a booster intervention in older adults with chronic diseases. Second, we evaluated the role of personal health records (PHR) prototype as the linkage between the clinic and community. Using input from these two objectives, we lay the groundwork for the Person-centered Wellness Home (PCWH).

Research Design And Methods: Participants enrolled from five South Bronx New York City Housing Authority communities. We conducted a pragmatic, randomized controlled trial using two arms ( = 121): (1) SMRCSGP and (2) SMRCSGP plus wellness coaching initiated as a booster after SMRCSGP completion. Adjusted individual growth models compared the slope differences for outcomes. We conducted a social networking analysis on the ties between wellness coaches and participants. PCMH-certified physicians completed in-depth interviews on the PHR prototype. An adaptation from the consensus-workshop model summarized the priority PCWH items.

Results: There was an improvement in self-reported physical functioning (2.0 T-score units higher, = .03) by the wellness coaching group, but the groups did not differ on physical activity. From the social networking analysis, connections were stable over time with wellness-coaches and participants. The Consensus Conference identified eight major components of the PCWH.

Discussion And Implications: Wellness coaching post-SMRCSGP was a booster to physical function, an upstream outcome for physical activity. During the Consensus-Conference, community-based prevention marketing and personal navigators for connecting to a PCMH emerged as novel components. This supports future work in training community health workers as peer leaders to provide evidence-based programs and other PCWH components.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geroni/igz055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974576PMC
January 2020

Health Literacy Among In-Care Older HIV Diagnosed Persons with Multimorbidity: MMP NYS (Excluding NYC).

AIDS Behav 2020 Apr;24(4):1092-1105

SUNY - School of Public Health, University at Albany, Rensselaer, NY, USA.

Older persons living with diagnosed HIV (PLWDH) are also at risk for age-related chronic conditions. With conflicting results on studies assessing health literacy and durable viral suppression, this study is the first in assessing this relationship using representative data on older in-care HIV-diagnosed persons with multimorbidity. Weighted data collected 2009-2014 from the Medical Monitoring Project (MMP) was used. Health literacy was assessed using the three-item Brief Health Literacy Screen (BHLS). The mean health literacy score was 11.22 (95% CI 10.86-11.59), and the mean multimorbidity was 4.75 (SE = 0.32). After adjusting, health literacy (OR 0.87, 95% CI 0.77-0.99) was found to be significantly associated with durable viral suppression. Adequate health literacy can help with achieving durable viral suppression. For these persons, addressing health literacy might increase their ability to access and navigate the healthcare system, thereby helping them stay engaged and maintain adherence to HIV care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-019-02627-0DOI Listing
April 2020

Health Literacy Among In-Care Older HIV Diagnosed Persons with Multimorbidity: MMP NYS (Excluding NYC).

AIDS Behav 2020 Apr;24(4):1092-1105

SUNY - School of Public Health, University at Albany, Rensselaer, NY, USA.

Older persons living with diagnosed HIV (PLWDH) are also at risk for age-related chronic conditions. With conflicting results on studies assessing health literacy and durable viral suppression, this study is the first in assessing this relationship using representative data on older in-care HIV-diagnosed persons with multimorbidity. Weighted data collected 2009-2014 from the Medical Monitoring Project (MMP) was used. Health literacy was assessed using the three-item Brief Health Literacy Screen (BHLS). The mean health literacy score was 11.22 (95% CI 10.86-11.59), and the mean multimorbidity was 4.75 (SE = 0.32). After adjusting, health literacy (OR 0.87, 95% CI 0.77-0.99) was found to be significantly associated with durable viral suppression. Adequate health literacy can help with achieving durable viral suppression. For these persons, addressing health literacy might increase their ability to access and navigate the healthcare system, thereby helping them stay engaged and maintain adherence to HIV care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-019-02627-0DOI Listing
April 2020

Takotsubo cardiomyopathy in a man with no trigger and multiple cardioembolic complications-A rare constellation.

Echocardiography 2019 May 7;36(5):975-979. Epub 2019 Apr 7.

Division of Cardiology, Rush University Medical Center, Chicago, Illinois.

Takotsubo Cardiomyopathy (TC) is an uncommon, transient, reversible cardiomyopathy, with a classic pattern of wall-motion abnormalities, usually seen in women after an emotional stressor. Despite its increased recognition, there remain gaps in the exact mechanisms, predisposing factors, and predictors of recovery; this is particularly true for males where the condition occurs far less frequently than in females. TC typically resolves within weeks, and the prognosis is favorable compared to acute coronary syndromes. Nonetheless, about 1% of cases may be complicated by left ventricular (LV) thrombus and embolism. Herein we describe an atypical case of a man with no obvious trigger, who developed TC with left ventricular thrombus and multiple embolic complications, but subsequently showed complete and full resolution. Multimodality imaging including echocardiography, cardiac CT and cardiac MRI was instrumental in this diagnostic dilemma, as well as useful in guiding treatment options and informing prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.14333DOI Listing
May 2019

Trajectories of childhood adversity and the risk of depression in young adulthood: Results from the Avon Longitudinal Study of Parents and Children.

Depress Anxiety 2019 07 18;36(7):596-606. Epub 2019 Mar 18.

Department of Epidemiology and Biostatistics, University at Albany School of Public Health, State University of New York, Rensselaer, New York.

Background: The significance of the timing and chronicity of childhood adversity for depression outcomes later in life is unclear. Identifying trajectories of adversity throughout childhood would allow classification of children according to the accumulation, timing, and persistence of adversity, and may provide unique insights into the risk of subsequent depression.

Methods: Using data from the Avon Longitudinal Study of Parents and Children, we created a composite adversity score comprised of 10 prospectively assessed domains (e.g., violent victimization, inter-parental conflict, and financial hardship) for each of eight time points from birth through age 11.5 years. We used semiparametric group-based trajectory modeling to derive childhood adversity trajectories and examined the association between childhood adversity and depression outcomes at the age of 18 years.

Results: Among 9,665 participants, five adversity trajectories were identified, representing stable-low levels (46.3%), stable-mild levels (37.1%), decreasing levels (8.9%), increasing levels (5.3%), and stable-high levels of adversity (2.5%) from birth through late childhood. Approximately 8% of the sample met criteria for probable depression at 18 years and the mean depression severity score was 3.20 (standard deviation = 3.95, range 0-21). The risk of depression in young adulthood was elevated in the decreasing (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.19-2.48), increasing (OR = 1.81, 95% CI = 1.15-2.86), and stable-high (OR = 1.80, 95% CI = 1.00-3.23) adversity groups, compared to those with stable-low adversity, when adjusting for potential confounders.

Conclusions: Children in trajectory groups characterized by moderate or high levels of adversity at some point in childhood exhibited consistently greater depression risk and depression severity, regardless of the timing of adversity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/da.22887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602824PMC
July 2019

uPAR isoform 2 forms a dimer and induces severe kidney disease in mice.

J Clin Invest 2019 04 2;129(5):1946-1959. Epub 2019 Apr 2.

Department of Medicine, Rush University Medical Center, Chicago, Illinois, USA.

Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis. In vivo, msuPAR2 transgenic mice exhibited signs of severe renal disease characteristic of FSGS with proteinuria, loss of kidney function, and glomerulosclerosis. Sequencing of the glomerular RNAs from msuPAR2-Tg mice revealed a differentially expressed gene signature that includes upregulation of the suPAR receptor Itgb3, encoding β3 integrin. Crossing msuPAR2-transgenic mice with 3 different integrin β3 deficiency models rescued msuPAR2-mediated kidney function. Further analyses indicated a central role for β3 integrin and c-Src in msuPAR2 signaling and in human FSGS kidney biopsies. Administration of Src inhibitors reduced proteinuria in msuPAR2-transgenic mice. In conclusion, msuPAR2 may play an important role in certain forms of scarring kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI124793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486353PMC
April 2019

Limiting Alcohol Outlet Density to Prevent Alcohol Use and Violence: Estimating Policy Interventions Through Agent-Based Modeling.

Am J Epidemiol 2019 04;188(4):694-702

Violence Prevention Research Program, Department of Emergency Medicine, University of California, Davis, Sacramento, California.

Increasing alcohol outlet density is well-documented to be associated with increased alcohol use and problems, leading to the policy recommendation that limiting outlet density will decrease alcohol problems. Yet few studies of decreasing problematic outlets and outlet density have been conducted. We estimated the association between closing alcohol outlets and alcohol use and alcohol-related violence, using an agent-based model of the adult population in New York City. The model was calibrated according to the empirical distribution of the parameters across the city's population, including the density of on- and off-premise alcohol outlets. Interventions capped the alcohol outlet distribution at the 90th to the 50th percentiles of the New York City density, and closed 5% to 25% of outlets with the highest levels of violence. Capping density led to a lower population of light drinkers (42.2% at baseline vs. 38.1% at the 50th percentile), while heavy drinking increased slightly (12.0% at baseline vs. 12.5% at the 50th percentile). Alcohol-related homicides and nonfatal violence remained unchanged. Closing the most violent outlets was not associated with changes in alcohol use or related problems. Results suggest that focusing solely on closing alcohol outlets might not be an effective strategy to reduce alcohol-related problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwy289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438810PMC
April 2019

Use of ultrasound enhancing agents in transesophageal echocardiography to improve interpretive confidence of left atrial appendage thrombus.

Echocardiography 2019 02 19;36(2):362-369. Epub 2018 Dec 19.

Division of Cardiology, Rush University Medical Center, Chicago, Illinois.

Background: The value of ultrasound enhancing agents (UEA) in patients undergoing transesophageal echocardiography (TEE) for the exclusion of left atrial appendage (LAA) thrombi prior to direct current cardioversion (DCCV) is evolving.

Methods: We retrospectively identified 88 consecutive TEEs, where a commercial UEA was used during LAA interrogation. De-identified non-enhanced (pre-UEA) and enhanced cine loop images (post-UEA) from the same subjects were randomly reviewed by four expert readers in a blinded fashion.

Results: In 33% of the cases, UEA use was associated with a statistically insignificant improvement in physician confidence (scale, 0-3) in determining the presence or absence of a LAA thrombus (P = 0.071). In instances where non-enhanced images yielded an uncertain interpretation or when the left atrium contained spontaneous echo contrast (SEC), UEA use was associated with an improvement in interpretive confidence in 49% (P < 0.001) and 41% of the cases (P = 0.001), respectively. Overall, the absolute rate of hypothetical decision to proceed with DCCV rose by 9% with the application of UEA (P = 0.004). In instances where non-enhanced images were interpreted with limited confidence or when SEC was present, there were absolute increases of 16% (P < 0.001) and 21% (P < 0.001) in hypothetical procession to DCCV, respectively. In cases of a combination of limited interpretive confidence and SEC, UEA use was associated with a 29% absolute increase in the rate of procession to DCCV (P < 0.001).

Conclusions: In patients undergoing TEE interrogation of the LAA, the use of UEA is associated with an increase in the level of interpretive confidence and higher rates of theoretical procession to DCCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.14228DOI Listing
February 2019

Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab.

BMC Nephrol 2018 12 17;19(1):361. Epub 2018 Dec 17.

Department of Medicine, Rush University Medical Center, 1735 W Harrison ST, Cohn Bldg, 7th Floor, Suite 716, Chicago, IL, 60612, USA.

Background: Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS.

Methods: A retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte β3- integrin activity.

Results: Treatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte β3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05.

Conclusions: Serum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-018-1177-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296111PMC
December 2018

Assessing the impact of alcohol taxation on rates of violent victimization in a large urban area: an agent-based modeling approach.

Addiction 2019 02 16;114(2):236-247. Epub 2018 Nov 16.

Department of Population Health, NYU Langone Health, New York, NY, USA.

Aims: To use simulation to estimate the impact of alcohol taxation on drinking, non-fatal violent victimization and homicide in New York City (NYC). We simulate the heterogeneous effects of alcohol price elasticities by income, level of consumption and beverage preferences, and examine whether taxation can reduce income inequalities in alcohol-related violence.

Design: Agent-based modeling simulation.

Setting: NYC, USA.

Participants: Adult population aged 18-64 years in the year 2000 in the 59 community districts of NYC. The population of 256 500 agents approximates a 5% sample of the NYC population.

Measurements: Agents were parameterized through a series of rules that governed alcohol consumption and engagement in violence. Six taxation interventions were implemented based on extensive reviews and meta-analyses, increasing universal alcohol tax by 1, 5 and 10%, and beer tax by 1, 5 and 10%.

Findings: Under no tax increase, approximately 12.2% [95% credible interval (prediction interval, PI) = 12.1-12.3%] were heavy drinkers. Taxation decreased the proportion of heavy drinkers; a 10% tax decreased heavy drinking to 9.6% (95% PI = 9.4-9.8). Beer taxes had the strongest effect on population consumption. Taxation influenced those in the lowest income groups more than the highest income groups. Alcohol-related homicide decreased from 3.22 per 100 000 (95% PI = 2.50-3.73) to 2.40 per 100 000 under a 10% universal tax (95% PI = 1.92-2.94). This translates into an anticipated benefit of ~1200 lives/year.

Conclusion: Reductions in alcohol consumption in a large urban environment such as New York City can be sustained with modest increases in universal taxation. Alcohol tax increases also have a modest effect on alcohol-related violent victimization. Taxation policies reduce income inequalities in alcohol-related violence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/add.14470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314891PMC
February 2019

Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD.

Clin J Am Soc Nephrol 2018 07 14;13(7):1013-1021. Epub 2018 Jun 14.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;

Background And Objectives: Black Americans with and without kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.

Design, Setting, Participants, & Measurements: Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.

Results: At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; <0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; <0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; =0.003). suPAR was only associated with worsening proteinuria in patients with two risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; =0.02).

Conclusions: Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without kidney disease risk variants, independently of proteinuria and GFR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.13631217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032570PMC
July 2018

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High-Sensitivity C-Reactive Protein.

J Am Heart Assoc 2018 05 1;7(9). Epub 2018 May 1.

Centers for Diabetes Research and Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Type 2 diabetes mellitus is a major risk factor for cardiovascular disease; however, outcomes in individual patients vary. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow-derived signaling molecule associated with adverse cardiovascular and renal outcomes in many populations. We characterized the determinants of suPAR in African Americans with type 2 diabetes mellitus and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium (CAC), and high-sensitivity C-reactive protein (hs-CRP).

Methods And Results: We measured plasma suPAR levels in 500 African Americans with type 2 diabetes mellitus enrolled in the African American-Diabetes Heart Study. We used Kaplan-Meier curves and Cox proportional hazards models adjusting for clinical characteristics, CAC, and hs-CRP to examine the association between suPAR and all-cause mortality. Last, we report the change in C-statistics comparing the additive values of suPAR, hs-CRP, and CAC to clinical models for prediction of mortality. The suPAR levels were independently associated with female sex, smoking, insulin use, decreased kidney function, albuminuria, and CAC. After a median 6.8-year follow-up, a total of 68 deaths (13.6%) were recorded. In a model incorporating suPAR, CAC, and hs-CRP, only suPAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63-4.34). Addition of suPAR to a baseline clinical model significantly improved the C-statistic for all-cause death (Δ0.05, 95% confidence interval 0.01-0.10), whereas addition of CAC or hs-CRP did not.

Conclusions: In African Americans with type 2 diabetes mellitus, suPAR was strongly associated with mortality and improved risk discrimination metrics beyond traditional risk factors, CAC and hs-CRP. Studies addressing the clinical usefulness of measuring suPAR concentrations are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.008194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015289PMC
May 2018

Hepatitis C virus status awareness and test results confirmation among people who inject drugs in Ukraine.

Int J Drug Policy 2018 07 12;57:11-17. Epub 2018 Apr 12.

Yale University School of Medicine, Section of Infectious Diseases, New Haven, CT, USA; Yale University School of Public Health, Division of Epidemiology of Microbial Diseases, New Haven, CT, USA; University of Malaya, Centre of Excellence on Research in AIDS (CERiA), Kuala Lumpur, Malaysia.

Background: Among the estimated 340,000 people who inject drugs (PWID) in Ukraine, HCV prevalence is approximately 70%. As HCV treatment availability increases, an assessment of the HCV treatment cascade is needed to guide HCV prevention and treatment strategies.

Methods: Opioid dependent PWID were interviewed and tested for HIV and HCV in five Ukrainian cities from January 2014 to March 2015. Logistic regression was used to examine the independent correlates of two cascade steps: a) anti-HCV positive status awareness; b) chronic HCV confirmation; and of c) annual HCV testing for PWID.

Results: Among 1613 PWID, 1002 (62.1%) had anti-HCV positive test result, of which 568 (56.7%) were aware of it before the study and 346 (34.5%) reported previous confirmatory testing for chronic HCV. Independent correlates of being aware they had anti-HCV positivity included: current [AOR: 3.08; 95%CI: 2.16-4.40] or prior [AOR: 1.85; 95%CI: 1.27-2.68] opioid agonistic treatment (OAT) experience, relative to no prior OAT, living in Lviv [AOR: 0.50; 95%CI: 0.31-0.81] or Odesa [AOR: 2.73; 95%CI: 1.51-4.93] relative to Kyiv and being aware of having HIV [AOR: 4.10; 95%CI: 2.99-5.62]. Independent correlates of confirming HCV infection among those who were aware of their anti-HCV positive status included: current OAT [AOR: 2.00; 95%CI: 1.24-3.23], relative to prior OAT, the middle income category [AOR: 1.74, 95%CI: 1.15-2.63], relative to the lowest, and receiving ART [AOR: 4.54; 95%CI: 2.85-7.23]. Among 1613 PWID, 918 (56.9%) were either HCV negative or not aware of their HCV positive status, of which 198 (21.6%) reported recent anti-HCV test (during last 12 month). Recent anti-HCV test in this group was associated with current [AOR: 7.17; 95%CI: 4.63-11.13] or prior [AOR: 2.24; 95%CI: 1.32-3.81] OAT experience, relative to no prior OAT.

Conclusion: Encouraging PWID to participate in OAT may be an effective strategy to diagnose and link PWID who are HCV positive to care. Among HIV negative participants, regular HCV testing may be ensured by participation in OAT. More studies are needed to assess HCV treatment utilization among PWID in Ukraine and OAT as a possible way to retain them in treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drugpo.2018.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994183PMC
July 2018

Social Support Moderates Effects of Natural Disaster Exposure on Depression and Posttraumatic Stress Disorder Symptoms: Effects for Displaced and Nondisplaced Residents.

J Trauma Stress 2018 04 5;31(2):223-233. Epub 2018 Apr 5.

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Social support is a known protective factor against the negative psychological impact of natural disasters. Most past research has examined how the effects of exposure to traumatic events influences whether someone meets diagnostic criteria for depression and posttraumatic stress disorder (PTSD); it has also suggested sequelae of disaster exposure depends on whether survivors are displaced from their homes. To capture the full range of the psychological impact of natural disasters, we examined the buffering effects of social support on depressive symptoms and cluster-specific PTSD symptoms, with consideration of displacement status. In a survey conducted 18 to 24 months after Hurricane Katrina, 810 adults exposed to the disaster reported the number of Katrina-related traumatic events experienced, perceived social support 2 months post-Katrina, and cluster-specific PTSD and depressive symptoms experienced since Katrina. Analyses assessed the moderating effects of social support and displacement and the conditional effects of displacement status. Social support significantly buffered the negative effect of Katrina-related traumatic events on depressive symptoms, B = -0.10, p = .001, and avoidance and arousal PTSD symptoms, B = -0.02, p = .035 and B = -0.02, p = .042, respectively. Three-way interactions were nonsignificant. Conditional effects indicated social support buffered development of depressive symptoms across all residents; however, the moderating effects of support on avoidance and arousal symptoms only appeared significant for nondisplaced residents. Results highlight the protective effects of disaster-related social support among nondisplaced individuals, and suggest displaced individuals may require more formal supports for PTSD symptom reduction following a natural disaster.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jts.22270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020825PMC
April 2018

Agent-Based Modeling in Public Health: Current Applications and Future Directions.

Annu Rev Public Health 2018 04 12;39:77-94. Epub 2018 Jan 12.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA; email:

Agent-based modeling is a computational approach in which agents with a specified set of characteristics interact with each other and with their environment according to predefined rules. We review key areas in public health where agent-based modeling has been adopted, including both communicable and noncommunicable disease, health behaviors, and social epidemiology. We also describe the main strengths and limitations of this approach for questions with public health relevance. Finally, we describe both methodologic and substantive future directions that we believe will enhance the value of agent-based modeling for public health. In particular, advances in model validation, comparisons with other causal modeling procedures, and the expansion of the models to consider comorbidity and joint influences more systematically will improve the utility of this approach to inform public health research, practice, and policy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-publhealth-040617-014317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937544PMC
April 2018

Cardiovascular Disease Biomarkers and suPAR in Predicting Decline in Renal Function: A Prospective Cohort Study.

Kidney Int Rep 2017 May 9;2(3):425-432. Epub 2017 Feb 9.

Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR) strongly predicts outcomes and incident chronic kidney disease (CKD) in patients with cardiovascular disease (CVD). Whether the association between suPAR and CKD is a reflection of its overall association with chronic inflammation and poor CVD outcomes is unclear. We examined whether CVD biomarkers, including high-sensitivity C-reactive protein (hs-CRP), fibrin-degradation products (FDPs), heat-shock protein 70 (HSP-70), and high-sensitivity troponin I (hs-TnI) were associated with a decline in kidney function in the Emory Cardiovascular Biobank cohort, in which suPAR levels were shown to be predictive of both incident CKD and CVD outcomes.

Methods: We measured suPAR, hs-CRP, HSP-70, FDP, and hs-TnI plasma levels in 3282 adults (mean age 63 years, 64% male, 75% estimated glomerular filtration rate [eGFR] >60 ml/min per 1.73 m). Glomerular filtration rate was estimated using Chronic Kidney Disease-Epidemiology Collaboration (eGFR) at enrollment (n = 3282) and follow-up (n = 2672; median 3.5 years). Urine protein by dipstick at baseline was available for 1335 subjects.

Results: There was a weak correlation among biomarkers (r range: 0.17-0.28). hs-CRP, FDPs, hs-TnI, and suPAR were independently associated with baseline eGFR and proteinuria. The median yearly decline in eGFR was -0.6 ml/min per 1.73 m. hs-CRP (β: -0.04;  = 0.46), FDPs (β: -0.13;  = 0.08), HSP-70 (β: 0.05;  = 0.84), or hs-TnI (β: -0.01;  = 0.76) were associated with eGFR decline. suPAR remained predictive of eGFR decline even after adjusting for all biomarkers.

Discussion: hs-CRP, FDP, HSP-70, and hs-TnI were not associated with eGFR decline. The specific association of suPAR with eGFR decline supported its involvement in pathways specific to the pathogenesis of kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2017.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678674PMC
May 2017

The mitigating effects of maternal social support and paternal involvement on the intergenerational transmission of violence.

Child Abuse Negl 2018 04 30;78:46-59. Epub 2017 Sep 30.

Department of Epidemiology and Biostatistics, University at Albany School of Public Health, State University of New York, 1 University Place, Rensselaer, NY 12144, United States.

Childhood maltreatment is a strong risk factor for subsequent violence, including violent behaviors in young adulthood and offspring maltreatment after becoming a parent. Little is known about the specific circumstances under which supportive relationships may help disrupt this cycle of violence throughout the life course. We conducted two complementary analyses to assess whether maternal social support in early childhood, and also paternal involvement in middle childhood, could prevent the intergenerational transmission of violence, using data from the Avon Longitudinal Study of Parents and Children (n=11,384). We found that higher levels of maternal social support in the postpartum period reduced the odds of offspring maltreatment at ages 0-8 years (OR=0.95, 95% CI 0.93-0.96). When classifying mothers according to their abuse history, this protective association of social support was observed among mothers with no history of childhood maltreatment and among those with only childhood maltreatment (and not postpartum intimate partner violence [IPV]), but not among mothers who reported IPV since the child's birth. We then extended our analysis of these offspring forward in time and found that paternal involvement at ages 9-10 years was associated with a reduced risk of offspring self-reported violent perpetration at ages 18-20 years (OR=0.85, 95% CI=0.77-0.94). This protective association was generally apparent among all subgroups of children, including those with a history of childhood maltreatment. Together these results highlight the protective influence of supportive relationships against the intergenerational transmission of violence, depending on abuse history, context, and timing, with important implications for the prevention of childhood maltreatment and mitigation of its negative effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chiabu.2017.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857207PMC
April 2018

Reducing Urban Violence: A Contrast of Public Health and Criminal Justice Approaches.

Epidemiology 2018 01;29(1):142-150

Background: Cities are investing millions in Cure Violence, a public health approach to reduce urban violence by targeting at-risk youth and redirecting conflict to nonviolent responses. The impact of such a program compared with criminal justice responses is unknown because experiments directly comparing criminal justice and public health approaches to violence prevention are infeasible with observational data. We simulated experiments to test the influence of two interventions on violence: (1) Cure Violence and (2) directed police patrol in violence hot spots.

Methods: We used an agent-based model to simulate a 5% sample of the New York City (NYC) adult population, with agents placed on a grid representing the land area of NYC, with neighborhood size and population density proportional to land area and population density in each community district. Agent behaviors were governed by parameters drawn from city data sources and published estimates.

Results: Under no intervention, 3.87% (95% CI, 3.84, 3.90) of agents were victimized per year. Implementing the violence interrupter intervention for 10 years decreased victimization by 13% (to 3.35% [3.32, 3.39]). Implementing hot-spots policing and doubling the police force for 10 years reduced annual victimization by about 11% (to 3.46% [3.42, 3.49]). Increasing the police force by 40% combined with implementing the violence interrupter intervention for 10 years decreased violence by 19% (to 3.13% [3.09, 3.16]).

Conclusions: Combined investment in a public health, community-based approach to violence prevention and a criminal justice approach focused on deterrence can achieve more to reduce population-level rates of urban violence than either can in isolation. See video abstract at, http://links.lww.com/EDE/B298.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EDE.0000000000000756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718925PMC
January 2018

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children.

JAMA Pediatr 2017 11 6;171(11):e172914. Epub 2017 Nov 6.

Department of Medicine, Rush University Medical Center, Chicago, Illinois.

Importance: Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults.

Objective: To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD.

Design, Setting, And Participants: Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016.

Exposures: Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy.

Main Outcomes And Measures: The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2.

Results: Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007).

Conclusions And Relevance: Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.2914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121753PMC
November 2017

Invited Commentary: Agent-Based Models-Bias in the Face of Discovery.

Am J Epidemiol 2017 07;186(2):146-148

Agent-based models (ABMs) have grown in popularity in epidemiologic applications, but the assumptions necessary for valid inference have only partially been articulated. In this issue, Murray et al. (Am J Epidemiol. 2017;186(2):131-142) provided a much-needed analysis of the consequence of some of these assumptions, comparing analysis using an ABM to a similar analysis using the parametric g-formula. In particular, their work focused on the biases that can arise in ABMs that use parameters drawn from distinct populations whose causal structures and baseline outcome risks differ. This demonstration of the quantitative issues that arise in transporting effects between populations has implications not only for ABMs but for all epidemiologic applications, because making use of epidemiologic results requires application beyond a study sample. Broadly, because health arises within complex, dynamic, and hierarchical systems, many research questions cannot be answered statistically without strong assumptions. It will require every tool in our store of methods to properly understand population dynamics if we wish to build an evidence base that is adequate for action. Murray et al.'s results provide insight into these assumptions that epidemiologists can use when selecting a modeling approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwx090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860003PMC
July 2017

A tripartite complex of suPAR, APOL1 risk variants and αβ integrin on podocytes mediates chronic kidney disease.

Nat Med 2017 Aug 26;23(8):945-953. Epub 2017 Jun 26.

Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.

Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels. Mechanistically, surface plasmon resonance studies identified high-affinity interactions between suPAR, APOL1 and αβ integrin, whereby APOL1 protein variants G1 and G2 exhibited higher affinity for suPAR-activated avb3 integrin than APOL1 G0. APOL1 G1 or G2 augments αβ integrin activation and causes proteinuria in mice in a suPAR-dependent manner. The synergy of circulating factor suPAR and APOL1 G1 or G2 on αβ integrin activation is a mechanism for CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nm.4362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019326PMC
August 2017