A young man with hematuria and difficulty urinating.
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ABSTRACT:
SUBMITTER: Urban R
PROVIDER: S-EPMC8548956 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
A young man with hematuria and difficulty urinating.
Urban Ray R Olsen Jon J Foster Troy T
Journal of the American College of Emergency Physicians open 20211027 5
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Project description:ImportanceYoung adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown.ObjectivesTo identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty.Design, setting, and participantsThis cohort study included US young adults aged 40 years or younger treated between 2006 and 2016. Eligible patients were treated for stage 0 to stage III breast cancer at institutions participating in the Young Women's Breast Cancer Study, which included a specialized cancer institute and 12 other academic and community hospitals. Patients who responded at baseline and returned a 1-year survey were included in analysis. Data were analyzed in March 2024.Main outcomes and measuresTrajectory modeling classified patterns of financial difficulty from baseline through 10 years postdiagnosis using the Cancer Rehabilitation Evaluation System (CARES) scale. Multinomial regression examined characteristics, including treatment-related arm morbidity, associated with each trajectory.ResultsA total 1008 patients were included (median [IQR] age at diagnosis, 36 [33-39] years; 60 Asian [6.0%], 35 Black [3.5%], 47 Hispanic [4.7%], 884 White [87.7%]); 840 patients were college graduates (83.3%), 764 were partnered at baseline (75.8%), 649 were nulliparous (64.4%), and 908 were without comorbidities at enrollment (90.1%). Patients' tumors were primarily stage I-II (778 [77.2%]), estrogen receptor/progesterone receptor-positive (754 [74.8%]), and ERBB2-negative (formerly HER2) (686 [68.1%]). Patients were more frequently treated with mastectomy than breast conservation (771 [76.5%] vs 297 [29.5%]; P < .001). A majority of patients received radiation therapy (627 [62.2%]), chemotherapy (760 [75.4%]), and endocrine therapy (610 [60.6%]). A total of 727 patients (72.1%) reported arm symptoms within 2 years of surgery. Three distinct trajectories of experiences with finances emerged: 551 patients (54.7%) had low financial difficulty (trajectory 1), 293 (29.1%) had mild difficulty that improved (trajectory 2), and 164 (16.3%) had moderate to severe difficulty peaking several years after diagnosis before improving (trajectory 3). Hispanic ethnicity (OR, 3.71; 95% CI, 1.47-9.36), unemployment at baseline and 1 year (OR, 2.66; 95% CI, 1.63-4.33), and arm symptoms (OR, 1.77; 95% CI, 1.06-2.96) were associated with increased odds of experiencing trajectory 3. Having a college degree (OR, 0.20; 95% CI, 0.12-0.34) or being partnered (OR, 0.24; 95% CI, 0.15-0.38) were associated with increased odds of experiencing trajectory 1.ConclusionIn this cohort study of young adults with breast cancer, we identified a subset of patients who experienced a high degree of financial difficulty persisting into early survivorship. Targeted interventions to mitigate financial toxicity-modifiable factors that include support for the employability or return to work support for those experiencing arm symptoms after treatment-are needed.
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Project description:Background and objectivesGlomerular hematuria has varied causes but can have a genetic basis, including Alport syndrome and IgA nephropathy.Design, setting, participants, & measurementsWe used summary statistics to identify genetic variants associated with hematuria in White British UK Biobank participants. Individuals with glomerular hematuria were enriched by excluding participants with genitourinary conditions. A strongly associated locus on chromosome 2 (COL4A4-COL4A3) was identified. The region was reimputed using the Trans-Omics for Precision Medicine Program followed by sequential rounds of regional conditional analysis, conditioning on previous genetic signals. Similarly, we applied conditional analysis to identify independent variants in the MHC region on chromosome 6 using imputed HLA haplotypes.ResultsIn total, 16,866 hematuria cases and 391,420 controls were included. Cases had higher urinary albumin-creatinine compared with controls (women: 13.01 mg/g [8.05-21.33] versus 12.12 mg/g [7.61-19.29]; P<0.001; men: 8.85 mg/g [5.66-16.19] versus 7.52 mg/g [5.04-12.39]; P<0.001) and lower eGFR (women: 88±14 versus 90±13 ml/min per 1.72 m2; P<0.001; men: 87±15 versus 90±13 ml/min per 1.72 m2; P<0.001), supporting enrichment of glomerular hematuria. Variants at six loci (PDPN, COL4A4-COL4A3, HLA-B, SORL1, PLLP, and TGFB1) met genome-wide significance (P<5E-8). At chromosome 2, COL4A4 p.Ser969X (rs35138315; minor allele frequency=0.00035; P<7.95E-35; odds ratio, 87.3; 95% confidence interval, 47.9 to 159.0) had the most significant association, and two variants in the locus remained associated with hematuria after conditioning for this variant: COL4A3 p.Gly695Arg (rs200287952; minor allele frequency=0.00021; P<2.16E-7; odds ratio, 45.5; 95% confidence interval, 11.8 to 168.0) and a common COL4A4 intron 25 variant (not previously reported; rs58261427; minor allele frequency=0.214; P<2.00E-9; odds ratio, 1.09; 95% confidence interval, 1.06 to 1.12). Of the HLA haplotypes, HLA-B (*0801; minor allele frequency=0.14; P<4.41E-24; odds ratio, 0.84; 95% confidence interval, 0.82 to 0.88) displayed the most statistically significant association. For remaining loci, we identified three novel associations, which were replicated in the deCODE dataset for dipstick hematuria (nearest genes: PDPN, SORL1, and PLLP).ConclusionsOur study identifies six loci associated with hematuria, including independent variants in COL4A4-COL4A3 and HLA-B. Additionally, three novel loci are reported, including an association with an intronic variant in PDPN expressed in the podocyte.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_04_26_CJN13711021.mp3.
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