Organisational initiatives to improve care in the prevention and management of cardiometabolic conditions: A scoping review.

AIM: Cardiometabolic conditions such as cardiovascular disease, type 2 diabetes, and chronic kidney disease contribute to multimorbidity, posing a global health challenge. However, existing healthcare frameworks often struggle to adequately address the intricate needs of individuals living with these conditions. The review aims to map existing research on cardiometabolic care initiatives for the primary and secondary prevention of metabolic conditions. DATA SYNTHESIS: A scoping review was conducted following the methodology of the Joanna-Briggs-Institute. We searched Medline, Embase, and CINAHL. The review primarily sought studies comparing the effectiveness of cardiometabolic services/clinics in primary or secondary prevention of cardiometabolic conditions with standard care. The data from these studies were charted and summarised in tabular form, with a narrative synthesis. The search identified 97 records across three databases, and 18 documents met inclusion criteria. Two studies addressed cardiometabolic care in primary prevention, while twelve focused on secondary prevention. Positive outcomes were observed in primary prevention, including reductions in waist circumference, body mass index, blood pressure, and cholesterol levels. For secondary prevention, the studies demonstrated positive metabolic outcomes, such as reductions in HbA1c, weight, blood pressure, and cholesterol levels. Additionally, data from the available studies reported improved adherence to diabetes care processes and the implementation of guideline-directed therapies. CONCLUSION: This scoping review highlights the potential benefits of services such as cardiometabolic clinics for primary and secondary prevention in metabolic conditions. Future studies should use standardised outcome measures and include details on the structure, staffing and treatment intensity of clinics to aid their wider implementation.

Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning.

BACKGROUND: Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. INSPIRE group assessed if machine learning could determine a hemodialysis (HD) patient's 180-day GIB hospitalization risk. METHODS: An eXtreme Gradient Boosting (XGBoost) and logistic regression model were developed using an HD dataset in United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations; others were negative. Models considered 1,303 exposures/covariates. Performance was measured using unseen testing data. RESULTS: Incidence of 180-day GIB hospitalization was 1.18% in HD population (n = 451,579), and 1.12% in testing dataset (n = 38,853). XGBoost showed area under the receiver operating curve (AUROC) = 0.74 (95% confidence interval (CI) 0.72, 0.76) versus logistic regression showed AUROC = 0.68 (95% CI 0.66, 0.71). Sensitivity and specificity were 65.3% (60.9, 69.7) and 68.0% (67.6, 68.5) for XGBoost versus 68.9% (64.7, 73.0) and 57.0% (56.5, 57.5) for logistic regression, respectively. Associations in exposures were consistent for many factors. Both models showed GIB hospitalization risk was associated with older age, disturbances in anemia/iron indices, recent all-cause hospitalizations, and bone mineral metabolism markers. XGBoost showed high importance on outcome prediction for serum 25 hydroxy (25OH) vitamin D levels, while logistic regression showed high importance for parathyroid hormone (PTH) levels. CONCLUSIONS: Machine learning can be considered for early detection of GIB event risk in HD. XGBoost outperforms logistic regression, yet both appear suitable. External and prospective validation of these models is needed. Association between bone mineral metabolism markers and GIB events was unexpected and warrants investigation. TRIAL REGISTRATION: This retrospective analysis of real-world data was not a prospective clinical trial and registration is not applicable.

Baseline, Early Changes, and Residual Albuminuria: Post-hoc Analysis of a Clinical Trial of Dapagliflozin in Chronic Kidney Disease.

BACKGROUND: Albuminuria is a strong indicator of kidney and cardiovascular risk in patients with chronic kidney disease (CKD). We assessed risk associations between albuminuria at baseline and four months after randomization in a placebo-controlled trial of dapagliflozin and kidney endpoints in patients with CKD and albuminuria, with and without type 2 diabetes. METHODS: In this post-hoc analysis of the DAPA-CKD trial, 4304 adult patients with CKD were randomized to dapagliflozin 10mg or placebo as adjunct to maximally tolerated renin-angiotensin-system (RAAS) inhibitors. The primary endpoint was a composite of sustained ≥50% decline in estimated glomerular filtration rate, kidney failure, or death from kidney or cardiovascular cause. The kidney composite endpoint was similar but excluded cardiovascular death. We assessed associations among baseline albuminuria, early change in albuminuria, (baseline to Month 4), and residual albuminuria (Month 4) with the primary composite and kidney composite endpoints using Cox proportional hazards regression analyses. RESULTS: Compared to placebo, dapagliflozin reduced urinary albumin-to-creatinine ratio (UACR; baseline to Month 4) by 36% (95% CI: 30.2%, 42.5%) and 21% (95% CI: 12, 30%) in participants with and without type 2 diabetes, respectively (p-interaction: 0.02). A reduction in UACR from baseline to Month 4 was associated with a lower risk for the primary and kidney composite endpoints with a similar risk gradient for participants with and without type 2 diabetes (p-interaction: 0.10 and 0.19, respectively). Residual albuminuria was associated with a similar risk for the primary and kidney composite endpoints in each treatment arm (p-interaction: 0.19 and 0.18, respectively). CONCLUSIONS: Dapagliflozin reduced albuminuria, and the magnitude of albuminuria reduction showed similar proportional reductions in risks for the primary and kidney composite endpoints in participants with and without type 2 diabetes. Patients with residual albuminuria at Month 4 - whether randomized to dapagliflozin or placebo - experienced relatively high rates of CKD progression kidney endpoints, suggesting that therapies added to RAAS inhibitors and dapagliflozin may be required to sustain kidney and cardiovascular health. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD), NCT03036150.

The Impact of Primary Renal Diagnosis on Prognosis and the Varying Predictive Power of Albuminuria in the NURTuRE-CKD Study.

INTRODUCTION: The definition of CKD is broad, which neglects the heterogeneity of risk across primary renal diseases. METHODS: The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD is an ongoing UK, prospective multicenter cohort study of 2,996 adults with an eGFR of 15-59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a urine albumin-to-creatinine ratio (uACR) >30 mg/mmol. Outcomes and predictive performance of eGFR and uACR were subcategorized by ERA-EDTA primary renal diagnosis (PRD) codes. RESULTS: 2,638 participants were included, with baseline median eGFR of 33.5 mL/min/1.73 m2 and uACR 29.8 mg/mmol. Over a median 49.2 months follow-up, 630 (23.9%) experienced kidney failure (KF), and 352 (13.3%) died before KF, the median eGFR slope was -1.97 mL/min/1.73 m2/year. There were significant differences in risk across the PRD, persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors (blood pressure, HbA1c, and renin-angiotensin-aldosterone system inhibitors). Diabetic kidney disease (DKD), glomerulonephritis, and familial/hereditary nephropathy were associated with the greatest risk, while tubulointerstitial disease and vasculitis carried a low risk of KF. eGFR had good predictive accuracy across all PRD. However, the addition of uACR showed variable benefit, depending on the PRD. The largest benefit was seen in vasculitis, renal vascular, and DKD groups, but uACR added no predictive value to the familial/hereditary group. CONCLUSION: Significant differences in the risk of kidney-related outcomes occurred across the various primary renal diagnoses persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors. Albuminuria's discriminatory ability as a biomarker of progression varies by diagnosis. CKD care should, therefore, take a personalized approach that always considers the primary renal diagnosis.

Neighborhood Disadvantage and Prostate Tumor Aggressiveness among African American and European American Men.

BACKGROUND: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race. METHODS: We evaluated associations between aggressive prostate cancer and four ND metrics-Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004-2021). RESULTS: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00-1.30; RI, OR = 1.27, CI, 1.07-1.51; redlining, OR = 1.77; CI, 1.23-2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13-1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men. CONCLUSIONS: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race. IMPACT: Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.

Modeling Historic Arsenic Exposures and Spatial Risk for Bladder Cancer.

Arsenic is a bladder carcinogen though less is known regarding the specific temporal relationship between exposure and bladder cancer diagnosis. In this study, we modeled time-varying mixtures of arsenic exposures at many historic temporal windows to evaluate their association with bladder cancer risk in the New England Bladder Cancer Study. We used arsenic exposure estimates up to 60 years prior to study entry and compared the goodness of fit of models using these mixtures to those using summary measures of arsenic exposures. We used the Bayesian index low rank kriging multiple membership model (LRK-MMM) to estimate the associations of these mixtures with bladder cancer and estimate cumulative spatial risk for bladder cancer using participants' residential histories. We found consistent evidence that modeling arsenic exposures as a time-varying mixture provided better fit to the data than using a single arsenic exposure summary measure. We estimated several positive though not significant associations of the time-varying arsenic mixtures with bladder cancer having odds ratios (ORs) of 1.03-1.14 and identified many significant and positive associations for an interaction among those who consumed water from a private dug well (ORs 1.28-1.60). Arsenic exposures 40-50 years before study entry received elevated importance weights in these mixtures. Additionally, we found two small areas of elevated cumulative spatial risk for bladder cancer in southern New Hampshire and in south central Maine. These results emphasize the importance of considering time-varying mixtures of exposures for diseases with long latencies such as bladder cancer.

Modeling the Effects of Policies that Restrict Tobacco Retail Outlets on Prenatal Smoke Exposure and Perinatal Health Care Utilization.

Tobacco retail outlet (TRO) density has been associated with increased cotinine levels in pregnant persons and their children. As such, the higher densities of TROs may represent higher levels of active smoking during pregnancy. The purpose of this study is to simulate the reduction in cotinine (a biomarker of smoke exposure) and health care utilization that could occur in pregnant persons under enactment of several candidate TRO reduction policy recommendations. Using existing retail outlet data from the state of North Carolina and from the Newborn Epigenetic Study (NEST), the present study created hypothetical policy-informed datasets of TROs that a) limited the number of TROs to the same density as the 2014 San Francisco (SF) policy (Policy 1), b) set the minimum distance to 500 feet between TROs from a school and from other TROs (Policy 2), c) restricted the types of TROs to exclude pharmacies (Policy 3), and d) a combination of Policies 1-3 (Policy 4). We estimated the effects of each policy individually and in a separate model with their combined effects in terms of the reduction on cotinine levels and health care utilization, as measured by number of visits to the emergency department (ED). We found that the hypothetical policies were likely to be effective in reducing maternal cotinine and ED visits, with the majority of the mothers in the dataset demonstrating reductions in these outcomes after implementation of the policies. We found that Policy 1 led to moderate reductions in TRO exposure for the majority of the sample as well as stratified by race/ethnicity. Additionally, Policy 4 had slightly larger estimated effects than Policy 1, but could be more onerous to implement in practice. Overall, we identified evidence supporting the efficacy of TRO reduction strategies that could impact smoke exposure during pregnancy in our diverse sample in North Carolina.

First interim results from FINE-REAL: a prospective, non-interventional, phase 4 study providing insights into the use and safety of finerenone in a routine clinical setting.

BACKGROUND: Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). The FINE-REAL study (NCT05348733) aims to evaluate the characteristics and treatment patterns of participants treated with finerenone in clinical practice. METHODS: FINE-REAL is a prospective, single-arm, non-interventional study of patients initiated on finerenone as part of their routine care in accordance with country-approved labels. The study, initiated in June 2022, is expected to be completed by January 2028. The cutoff for this pre-specified interim analysis was June 13, 2023. RESULTS: Participants were recruited across nephrology, endocrinology, cardiology, and primary care settings. Of 556 participants enrolled in the study by the cut-off date, 504 were included in this analysis (median follow-up duration of 7 months [finerenone treatment initiation to last recorded observation]). At baseline, 76.1% of participants were in the high or very high (KDIGO) CKD risk categories. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter 2 inhibitors were prescribed to 71.8% and 46.6% of participants, respectively. Based on prescribing information, 87.9% and 12.1% of participants initiated finerenone at doses of 10 and 20 mg, respectively. Finerenone treatment was uninterrupted in 92.3% of participants after 7 months' median follow-up. Treatment-emergent adverse events occurred in 110 (21.8%) participants. Hyperkalemia occurred in 25 (5.0%) participants, with no cases leading to death, dialysis, or hospitalization. CONCLUSION: At this interim analysis, finerenone was initiated in patients with CKD and T2D across various clinical practices participating in the study. Treatment discontinuation and hyperkalemia occurred infrequently.

Effects of Dapagliflozin in Patients with Membranous Nephropathy.

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial. Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR. Results: Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m2, and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event. Conclusion: In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease.

BACKGROUND: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models. RESULTS: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials. CONCLUSIONS: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.).

Ambient ultraviolet A, ultraviolet B and risk of melanoma in a nationwide United States cohort, 1984-2014.

BACKGROUND: Ultraviolet radiation (UVR) exposure is the primary risk factor for melanoma although the relationship is complex. Compared to radiation from UVB wavelengths, UVA makes up a majority of the surface solar UVR, penetrates the skin more deeply, is the principal range emitted by tanning beds, and is less filtered by sunscreens and window glass. Few studies have examined the relationship between ambient UVA and UVB and melanoma risk. METHODS: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for the association between satellite-based ambient (based on residential history) UVA, UVB and melanoma in non-Hispanic White participants using data from the United States Radiologic Technologists study, a large, nationwide prospective cohort. Associations of UVA and UVB quartile (Q) were examined in mutually adjusted and stratified models, additionally adjusted for demographic and sun sensitivity characteristics. RESULTS: There were 837 incident melanoma cases among 62,785 participants. Incidence of melanoma was statistically significantly increased for the highest quartile of childhood UVA exposure after adjustment for UVB (IRR = 2.82; 95%CI:1.46,5.44), but not for higher childhood UVB after adjustment for UVA. Childhood UVA was associated with increased melanoma risk within strata of UVB. Childhood UVB was not associated with melanoma after adjustment for UVA, but there was some evidence of lower risk with increased lifetime ambient UVB after UVA adjustment. CONCLUSIONS: Melanoma risk was elevated among participants living in locations with high annual childhood and lifetime UVA after controlling for UVB. With confirmation, these findings support increased protection from solar UVA for melanoma prevention.

The Together for Health - Virginia Research Program: A Multi-Modal Approach for Population Health Assessment.

Background: The Together for Health-Virginia (T4H-VA) Research Program aimed to advance cancer prevention, education, and outreach in Virginia. Creating a representative and inclusive cohort is critical to the program's mission and quality of outcomes. The T4H-VA Research Program utilized a multi-modal sampling approach to improve population health assessment. The current study describes the technology-based, non-probability platform developed for this purpose and compares differences between the probability-based (mail-based) and non-probability-based (e-cohort) methods with respect to participant demographics, health characteristics, and health information and technology use. Methods: T4H-VA is a research registry focusing on 54 counties within the Massey Comprehensive Cancer Center (MCCC) catchment area in Richmond, VA. Adult residents proficient in English were eligible. For the probability-based sampling, surveys were mailed to residents within the catchment area. For the non-probability sampling, an online study platform was developed and surveys were completed through the web/mobile app. Results: Both cohorts fell short of recruitment goals. The study yielded 1158 participants (M=57, SD=16 years; 55.0% female; 72.1% White); 899 (77.6%) were sampled through the probability, mail-based approach. Participants who identified as "other" race were significantly less likely to be sampled by the non-probability method. Significant differences emerged, including health protective (greater moderate and high physical activity) and risk factors (greater alcohol consumption and personal history of cancer) in the non-probability, e-cohort relative to the probability sample. E-Cohort participants were significantly more likely to report using electronic health records. Discussion: Overall difficulties in recruiting were caused, at least in part, by the onset of the COVID-19 pandemic and related factors. The e-cohort, which used exclusively digital recruitment strategies, fell significantly short of recruitment goals. This suggests in-person and mail-based strategies remain important for recruitment. Moreover, instead of favoring a singular approach, a combined approach to survey sampling may capitalize on the strengths of each sampling mode to increase diversity in sociodemographic and health risk characteristics.

The Broader Effects of Delayed Progression to End-Stage Kidney Disease: Delaying the Inevitable or a Meaningful Change?

A global rise in the prevalence of patients with chronic kidney disease (CKD) with end-stage kidney disease (ESKD) has led to a considerable and increasing burden to health systems, patients, and society. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are proven to reduce incidence of cardio-renal outcomes, including onset of ESKD. Recent post hoc analyses of SGLT2 inhibitor trials extrapolate substantial delays in the average time to ESKD over a patient's lifetime. In this article, we explore the possible real-world effects of such a delay by considering the available evidence reporting outcomes following onset of ESKD. From the patient perspective, a delay in reaching ESKD could substantially improve health-related quality of life and result in additional life years without the need for kidney replacement therapies, a target relevant to all CKD subpopulations. Furthermore, should a patient initiate dialysis at an older age as a result of CKD progression, the time spent in receipt of dialysis, and therefore associated healthcare costs, may also be reduced. A delay in progression may also lead to changes in the management of ESKD, such as increased election of conservative care in preference to dialysis, particularly in elderly populations. For younger patients with CKD, those who reach ESKD while employed face considerable work impairment and productivity loss, as may families and care partners of working age. Therefore, a delay to the onset of ESKD will reduce the proportion of their working lives affected by productivity losses or unemployment due to medical reasons. In conclusion, optimised treatment of CKD may lead to a shift in treatment options, but proper and timely implementation is essential for the realisation of improved outcomes.

The Lived Experience of Patients with Chronic Kidney Disease: Insights From DISCOVER CKD.

INTRODUCTION: Chronic kidney disease (CKD) can have a profound impact on patients' lives. However, multinational data on patients' lived experience with CKD are scarce. METHODS: Individuals from the prospective cohort of DISCOVER CKD (NCT04034992), an observational cohort study, were recruited to participate in one-to-one telephone interviews to explore their lived experience with CKD. A target of 100 participant interviews was planned across four countries (Japan, Spain, the UK, and the USA). These qualitative interviews, lasting ∼60-90 min, were conducted in the local language by trained interviewers with specific experience in CKD, between January and June 2023. Transcribed interviews were translated into English for coding and analysis. Data were coded using qualitative research software. RESULTS: Of the 105 participants interviewed, 103 were included in the final analysis. The average time since CKD diagnosis was 9.5 years, and at least half (50.5%) of participants had CKD stage 3A or 3B. CKD diagnosis was an emotional experience, driven by worry (n = 29/103; 28.2%) and shock (n = 26/103; 25.2%), and participants often reported feeling inadequately informed. Additional information was frequently sought, either online or via other healthcare providers. The proportion of participants reporting no impacts of CKD on their lives was highest in those with CKD stage 1 and 2 (64.3%). Conversely, every participant in the CKD stage 5 on dialysis group reported some impact of CKD on their lives. Across all participants, the most reported impacts were anxiety or depression (37.9%) or ability to sleep (37.9%). The frequency of the reported impacts appeared to increase with disease severity, with the highest rates observed in the dialysis group. In that group, the most frequently reported impact was on the ability to work (80.0%). CONCLUSION: Findings from this multinational qualitative study suggest that patients may experience symptoms and signs of disease prior to diagnosis; however, these are often nonspecific and may not be directly associated with CKD. Once diagnosed, the burden of CKD can have a diverse, negative impact on various aspects of patients' lives. This highlights the need for early identification of at-risk individuals, and the importance of early CKD diagnosis and management with guideline-directed therapies to either prevent further deterioration of CKD or slow its progression, thus reducing symptom burden and improving quality of life.

The Association Between a Neighborhood Adverse Childhood Experiences Index and Body Mass Index Among New York City Youth.

Background: The role of neighborhood factors in the association between adverse childhood experiences (ACEs) and body mass index (BMI) has not been widely studied. A neighborhood ACEs index (NAI) captures neighborhood environment factors associated with ACE exposure. This study examined associations between BMI and an NAI among New York City (NYC) youth. An exploratory objective examined the NAI geographic distribution across NYC neighborhoods. Methods: Data for students attending NYC public general education schools in kindergarten-12th grade from 2006-2017 (n = 1,753,867) were linked to 25 geospatial datasets capturing neighborhood characteristics for every census tract in NYC. Multivariable hierarchical linear regression tested associations between BMI and the NAI; analyses also were conducted by young (<8 years), school age (8-12 years), and adolescent (>12 years) subgroups. In addition, NAI was mapped by census tract, and local Moran's I identified clusters of high and low NAI neighborhoods. Results: Higher BMI was associated with higher NAI across all sex and age groups, with largest magnitude of associations for girls (medium NAI vs. low NAI: unstandardized ß = 0.112 (SE 0.008), standardized ß [effect size]=0.097, p < 0.001; high NAI vs. low NAI: unstandardized ß = 0.195 (SE 0.008), standardized ß = 0.178, p < 0.001) and adolescents (medium NAI vs. low NAI: unstandardized ß = 0.189 (SE 0.014), standardized ß = 0.161, p < 0.001, high NAI vs. low NAI: unstandardized ß = 0.364 (SE 0.015), standardized ß = 0.334, p < 0.001 for adolescent girls; medium NAI vs. low NAI: unstandardized ß = 0.122 (SE 0.014), standardized ß = 0.095, p < 0.001, high NAI vs. low NAI: unstandardized ß = 0.217 (SE 0.015), standardized ß = 0.187, p < 0.001 for adolescent boys). Each borough of NYC included clusters of neighborhoods with higher and lower NAI exposure, although clusters varied in size and patterns of geographic dispersion across boroughs. Conclusions: A spatial index capturing neighborhood environment factors associated with ACE exposure is associated with higher BMI among NYC youth. Findings complement prior literature about relationships between neighborhood environment and obesity risk, existing research documenting ACE-obesity associations, and the potential for neighborhood factors to be a source of adversity. Collectively, evidence suggests that trauma-informed place-based obesity reduction efforts merit further exploration as potential means to interrupt ACE-obesity associations.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04034992.

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes.

Importance: African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. Objective: To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. Design, Setting, and Participants: This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Exposures: Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. Main Outcomes and Measures: A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. Results: A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (ß = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, ß = 0.008; SE, 0.003; P = .01; q value = .21). Conclusions and Relevance: In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials.

BACKGROUND: SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with type 2 diabetes. We sought to evaluate whether the benefits of SGLT2 inhibitors are consistent in patients receiving and not receiving GLP-1 receptor agonists. METHODS: We conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, restricted to participants with diabetes. Treatment effects from individual trials were obtained from Cox regression models and pooled using inverse variance weighted meta-analysis. The two main cardiovascular outcomes assessed included major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and hospitalisation for heart failure or cardiovascular death. The main kidney outcomes assessed were chronic kidney disease progression (≥40% decline in estimated glomerular filtration rate [eGFR], kidney failure [eGFR <15 mL/min/1·73 m2, chronic dialysis, or kidney transplantation], or death due to kidney failure), and the rate of change in eGFR over time. Safety outcomes were also assessed. FINDINGS: Across 12 randomised, double-blind, placebo-controlled trials, 3065 (4·2%) of 73 238 participants with diabetes were using GLP-1 receptor agonists at baseline. SGLT2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists (hazard ratio [HR] 0·81, 95% CI 0·63-1·03 vs 0·90, 0·86-0·94; p-heterogeneity=0·31). Effects on hospitalisation for heart failure or cardiovascular death (0·76, 0·57-1·01 vs 0·78, 0·74-0·82; p-heterogeneity=0·90) and chronic kidney disease progression (0·65, 0·46-0·94 vs 0·67, 0·62-0·72; p-heterogeneity=0·81) were also consistent regardless of GLP-1 receptor agonist use, as was the effect on the chronic rate of change in eGFR over time (heterogeneity=0·92). Fewer serious adverse events occurred with SGLT2 inhibitors compared with placebo, irrespective of GLP-1 receptor agonist use (relative risk 0·87, 95% CI 0·79-0·96 vs 0·91, 0·89-0·93; p-heterogeneity=0·41). INTERPRETATION: The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes. FUNDING: National Health and Medical Research Council of Australia and the Ramaciotti Foundation.