Getting the word out: Methods of learning about research and motivations for participation in a study focusing on a reproductive-aged Latina/x population.

Background: Although one of the fastest-growing populations in the USA, Latinx individuals remain underrepresented in research. In this study, we aimed to identify how Latina/Latinx participants of the Environment, Leiomyomas, Latinas, and Adiposity Study (ELLAS) learned about the research study and what motivated them to participate. Materials and Methods: Using a standardized survey tool, bilingual staff interviewed participants and asked them, 1) how they heard about ELLAS and 2) to identify and rank their top three reasons for participating in ELLAS. Results: "Word of mouth" through a friend or relative was the most common method of learning about ELLAS (49.0%), followed by a "community outreach event" (29.3%). The three most common reasons for participating in ELLAS were "to learn more about women's health" (83.3%), "to receive a free health assessment" (79.4%), and "to contribute to scientific knowledge" (59.5%). Correlation between demographic and socioeconomic characteristics and participant responses indicated that there are different reasons for participation based on these factors. Conclusions: Community engagement and word of mouth are vital to the successful recruitment of Latina/Latinx participants to research studies. Latinx participants are most motivated to participate by health benefits and health education, as well as altruistic aspects of research studies. Therefore, establishing mutually beneficial relationships within Latinx communities and appealing to motivations for research participation with close attention to the demographics of participants can both expand and allow for targeted recruitment efforts for this underrepresented group in research studies.

Association between uterine fibroids and antimüllerian hormone concentrations among African American women.

OBJECTIVE: To evaluate the extent to which uterine fibroids are associated with antimüllerian hormone (AMH) concentrations. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle, and Fibroids, which is a 5-year longitudinal study of African American women. PATIENT(S): A total of 1,643 women aged 23-35 years without a known history of fibroids. EXPOSURE: Fibroid presence. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was percent difference in the mean AMH concentration between participants with fibroids and those without fibroids. The secondary outcomes were percent differences in the mean AMH concentrations in participants with different numbers, sizes, types, and positions of fibroids and the percent difference in the mean AMH concentration in participants with different uterine volumes. RESULT(S): At least 1 fibroid was identified on ultrasound in 362 (22%) participants. There was a small difference in the mean AMH concentrations in participants with fibroids (age-adjusted model: -4.6%, 95% confidence interval (CI): -14.5% to 6.5%; multivariable model: -4.6%, 95% CI: -14.4% to 6.3%). The mean AMH concentrations were found to decrease with increasing fibroid number. Although differences in AMH concentrations were not statistically significant, compared with no fibroids, the mean percent differences in AMH concentrations for 1, 2-3, and ≥4 fibroids were -1.2% (95% CI: -13.2% to 12.5%), -7.1% (95% CI: -23.3% to 12.5%), and -17.5% (95% CI: -38.2% to 10.0%), respectively. There were no consistent associations between AMH concentrations and fibroid location, size, or uterine volume. CONCLUSION(S): The presence of fibroids was not materially associated with AMH concentrations. Other than a monotonic inverse relationship between fibroid number and AMH concentrations, no other fibroid characteristics were consistently or appreciably associated, although associations were imprecise.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels.

OBJECTIVE: To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. PATIENT(S): The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. RESULT(S): In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. CONCLUSION(S): The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Inpatient Pediatric CKD Health Care Utilization and Mortality in the United States.

RATIONALE & OBJECTIVE: The impact of chronic kidney disease (CKD) on inpatient health care use is unknown. This study aimed to describe the prevalence of pediatric CKD among children hospitalized in the United States and examine the association of CKD with hospital outcomes. STUDY DESIGN: Cross-sectional national survey of pediatric discharges. SETTING & PARTICIPANTS: Hospital discharges of children (aged>28 days to 19 years) with a chronic medical diagnosis included in the Healthcare Cost and Utilization Project Kids' Inpatient Database for 2006, 2009, 2012, and 2016. PREDICTOR: Presence of primary or coexisting CKD as identified by diagnosis codes. OUTCOMES: Length of stay (LOS), cost, and mortality. ANALYTICAL APPROACH: Multivariable analysis using Poisson, gamma, and logistic regressions were performed for LOS, cost, and mortality, respectively. RESULTS: A chronic medical condition was present in 6,524,745 estimated discharges during the study period and CKD was present among 3.9% of discharges (96.1% without CKD). Those with CKD had a longer LOS (median of 2.8 [IQR, 1.4-6.0] days compared with 1.8 [IQR, 1.0-4.4] days for those without a CKD diagnosis; P<0.001). Median cost was higher in the CKD group compared with the group without CKD, at $8,755 (IQR, $4,563-18,345) and $5,016 (IQR, $2,860-10,109) per hospitalization, respectively (P<0.001). Presence of CKD was associated with a longer LOS (29.9% [95% CI, 27.2%-32.6%] longer than those without CKD), higher cost (61.3% [95% CI, 57.4%-65.4%] greater than those without CKD), and higher risk for mortality (OR, 1.51 [95% CI, 1.40-1.63]). LIMITATIONS: Lack of access to and adjustment for confounders including patient readmission and laboratory data. CONCLUSIONS: Pediatric CKD was associated with longer LOS, higher costs, and higher risk for mortality compared with hospitalizations with other chronic illnesses. Further studies are needed to better understand the health care needs and delivery of care to hospitalized children with CKD.

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network.

BACKGROUND: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). METHODS: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. RESULTS: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). CONCLUSIONS: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

Time to Initiation of Antihypertensive Therapy After Onset of Elevated Blood Pressure in Patients With Primary Proteinuric Kidney Disease.

RATIONALE & OBJECTIVE: The objective of the study was to estimate the prevalence of hypertension in patients with proteinuric kidney disease and evaluate blood pressure (BP) control. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data from adults and children with proteinuric kidney disease enrolled in the multicenter Kidney Research Network Registry were used for this study. EXPOSURE: Proteinuric kidney disease. OUTCOMES: Hypertension and BP control. ANALYTICAL APPROACH: Patients with white-coat hypertension were excluded. Patients were censored at end-stage kidney disease onset. Patients were defined as hypertensive either by hypertension diagnosis code, having 2 or more encounters with elevated BPs, or treatment with antihypertensive therapy excluding renin-angiotensin-aldosterone system blockade. Elevated BP was defined as greater than 95th percentile for children and >140/90 mm Hg in adults. Sustained BP control was defined as 2 or more consecutive encounters with BPs lower than 95th percentile for children and <140/90 mm Hg for adults. Kaplan-Meier and Cox proportional hazards analyses were used to evaluate the time to initiation of antihypertensive therapy. RESULTS: 842 patients, 69% adults and 31% children, with a total observation period of 6,722 patient-years were included in the analysis. 644 (76%) had hypertension during observation. There was no difference in the prevalence of hypertension between children and adults (74% vs 78%; P = 0.3). Hypertension was most common among those of African American race compared with other races (90% vs 72%-75%; P = 0.003). 504 (78%) patients with hypertension achieved BP control but only 51% achieved control within 1 year. 140 (22%) patients with hypertension never achieved BP control during a median of 41 (IQR, 24-73) months of observation. LIMITATIONS: Differing BP control goals that may lead to overestimation of the controlled patient population. CONCLUSIONS: Hypertension affects most patients with proteinuric kidney disease regardless of age. Time to BP control exceeded 1 year in 50% of patients with hypertension and 22% did not demonstrate control. This study highlights the need to address hypertension early and completely in disease management of patients with proteinuric kidney disease.

Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome.

INTRODUCTION: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. METHODS: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time. RESULTS: Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001). CONCLUSION: uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.

Steroid-Associated Side Effects in Patients With Primary Proteinuric Kidney Disease.

INTRODUCTION: The goal of this study was to assess the occurrence of steroid-associated adverse events (SAAE) in patients with primary proteinuric kidney disease. METHODS: The Kidney Research Network Registry consists of children and adults with primary proteinuric kidney disease. SAAEs of interest were hypertension, hyperglycemia and diabetes, overweight and obesity, short stature, ophthalmologic complications, bone disorders, infections, and psychosis. Events were identified using International Classification of Diseases, Ninth Revision/Tenth Revision codes, blood pressures, growth parameters, laboratory values, and medications. Poisson generalized estimating equations tested the association between steroid onset and dose on SAAE risk. RESULTS: A total of 884 participants were included in the analysis; 534 (60%) were treated with steroids. Of these, 62% had at least one SAAE. The frequency of any SAAE after initiation of steroids was 293 per 1000 person-years. The most common SAAEs were hypertension (173.7 per 1000 person-years), diabetes (78.7 per 1000 person-years), obesity (66.8 per 1000 person-years), and infections (46.1 per 1000 person-years). After adjustment for demographics, duration of kidney disease, estimated glomerular filtration rate (eGFR), proteinuria, and other therapies, steroid exposure was associated with a 40% increase in risk of any SAAE (Relative risk [RR]: 1.4; 95% confidence interval [CI]: 1.3-1.6). A 1-mg/kg per day increase in steroid dose was associated with a 2.5-fold increase in risk of any SAAE. CONCLUSION: Most patients with primary proteinuric kidney disease treated with steroids experienced at least one SAAE. Steroid therapy increased risk of hypertension, diabetes, weight gain, short stature, fractures, and infections after adjusting for disease-related factors. This study highlights the importance of surveillance and management of SAAE and provides rationale for the development of steroid minimization protocols.

NephCure Accelerating Cures Institute: A Multidisciplinary Consortium to Improve Care for Nephrotic Syndrome.

INTRODUCTION: NephCure Accelerating Cures Institute (NACI) is a collaborative organization sponsored by NephCure Kidney International and the University of Michigan. The Institute is composed of 7 cores designed to improve treatment options and outcomes for patients with glomerular disease: Clinical Trials Network, Data Warehouse, Patient-Reported Outcomes (PRO) and Endpoints Consortium, Clinical Trials Consulting Team, Quality Initiatives, Education and Engagement, and Data Coordinating Center. METHODS: The Trials Network includes 22 community- and hospital-based nephrology practices, 14 of which are trial-only sites. Eight sites participate in the NACI Registry, and as of October 2017, 1054 patients are enrolled with diagnoses including but not limited to focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, IgA nephropathy, and childhood-onset nephrotic syndrome. By using electronic health record data extraction, robust and efficient clinical data are captured while minimizing the burden to site-based network staff. RESULTS: The Data Warehouse includes her-extracted data from registry patients, PRO development data, and data from completed observational studies and clinical trials. The Clinical Trial Consulting Team provides support for trial design in rare diseases leveraging these data. The PRO and Endpoints Consortium develops shorter-term endpoints while capturing the patient-reported significance of interventions under study. The Quality Initiatives and Education/Engagement cores elevate the level of care for patients. The Data Coordinating Center manages the analysis and operations of the Institute. CONCLUSION: By engaging with patients, academia, industry, and patient advocate community representatives, including our Patient Advisory Board, NACI strives for better outcomes and treatments using evidence-based support for clinical trial design.