Sujet(s)
Autochtones d'Alaska , Indiens d'Amérique Nord , Insuffisance rénale chronique , Humains , Insuffisance rénale chronique/ethnologie , Insuffisance rénale chronique/épidémiologie , Autochtones d'Alaska/statistiques et données numériques , Indiens d'Amérique Nord/statistiques et données numériques , États-Unis/épidémiologieRÉSUMÉ
Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99-2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45-7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.
Sujet(s)
Surveillance ambulatoire de la pression artérielle , Maladies cardiovasculaires , Insuffisance rénale chronique , Pronostic , Insuffisance rénale chronique/diagnostic , Insuffisance rénale chronique/épidémiologie , Risque , Maladies cardiovasculaires/diagnostic , Maladies cardiovasculaires/épidémiologie , Périodicité , Humains , Mâle , Femelle , Adulte d'âge moyen , Sujet âgéRÉSUMÉ
RATIONALE & OBJECTIVE: The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not treated with dialysis. PREDICTORS: Measurement of 448 known plasma metabolites. OUTCOMES: The uremic symptoms of fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 instrument. ANALYTICAL APPROACH: Multivariable adjusted linear regression, least absolute shrinkage and selection operator linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected in at least 2 of the 3 modeling approaches were deemed "overall significant." RESULTS: Participant mean estimated glomerular filtration rate was 43mL/min/1.73m2, with 44% self-identifying as female and 41% as non-Hispanic Black. The prevalence of uremic symptoms ranged from 22% to 55%. We identified 17 metabolites for which a higher level was associated with greater severity of at least one uremic symptom and 9 metabolites inversely associated with uremic symptom severity. Many of these metabolites exhibited at least a moderate correlation with estimated glomerular filtration rate (Pearson's r≥0.5), and some were also associated with the risk of developing kidney failure or death in multivariable adjusted Cox regression models. LIMITATIONS: Lack of a second independent cohort for external validation of our findings. CONCLUSIONS: Metabolomic profiling was used to identify multiple solutes associated with uremic symptoms in adults with CKD, but future validation and mechanistic studies are needed. PLAIN-LANGUAGE SUMMARY: Individuals living with chronic kidney disease (CKD) often experience symptoms related to CKD, traditionally called uremic symptoms. It is likely that CKD results in alterations in the levels of numerous circulating substances that, in turn, cause uremic symptoms; however, the identity of these solutes is not known. In this study, we used metabolomic profiling in patients with CKD to gain insights into the pathophysiology of uremic symptoms. We identified 26 metabolites whose levels were significantly associated with at least one of the symptoms of fatigue, anorexia, itchiness, nausea, paresthesia, and pain. The results of this study lay the groundwork for future research into the biological causes of symptoms in patients with CKD.
Sujet(s)
Insuffisance rénale chronique , Urémie , Humains , Femelle , Mâle , Urémie/complications , Urémie/sang , Insuffisance rénale chronique/complications , Insuffisance rénale chronique/sang , Insuffisance rénale chronique/épidémiologie , Études transversales , Adulte d'âge moyen , Sujet âgé , Études de cohortes , Prurit/étiologie , Prurit/épidémiologie , Prurit/sang , Fatigue/étiologie , Fatigue/sang , Fatigue/épidémiologie , Métabolomique , Nausée/épidémiologie , Qualité de vie , Paresthésie/étiologie , Paresthésie/épidémiologie , Débit de filtration glomérulaireRÉSUMÉ
PURPOSE: American Indian/Alaska Native (AI/AN) populations have some of the lowest cancer screening rates compared to other racial/ethnic populations. Using community-based participatory research methods, we sought to characterize knowledge, attitudes, beliefs, and approaches to enhance breast, colorectal, and cervical cancer screening. METHODS: We conducted 12 focus groups between October 2018 and September 2019 with 96 eligible AI adults and healthcare providers, recruited using non-probability purposive sampling methods from the Zuni Pueblo in rural New Mexico. We used the Multi-level Health Outcomes Framework (MHOF) to conduct a qualitative content analysis identifying mutable systems- and individual- level constructs important for behavior change that we crosslinked with the Community Preventive Services Task Force (CPSTF) recommended evidence-based interventions (EBIs) or approaches. RESULTS: Salient systems-level factors that limited uptake of cancer screenings included inflexible clinic hours, transportation barriers, no on-demand service and reminder systems, and brief doctor-patient encounters. Individual-level barriers included variable cancer-specific knowledge that translated into fatalistic beliefs, fear, and denial. Interventions to enhance community demand and access for screening should include one-on-one and group education, small media, mailed screening tests, and home visitations by public health nurses. Interventions to enhance provider delivery of screening services should include translation and case management services. CONCLUSIONS: The MHOF constructs crosslinked with CPSTF recommended EBIs or approaches provided a unique perspective to frame barriers and promoters of screening utilization and insights for intervention development. Findings inform the development of culturally tailored, theoretically informed, multi-component interventions concordant with CPSTF recommended EBIs or approaches aimed at improving cancer screening.
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Tumeurs colorectales , Indiens d'Amérique Nord , Tumeurs du col de l'utérus , Femelle , Adulte , Humains , Population d'origine amérindienne , Accessibilité des services de santé , Nouveau Mexique , Dépistage précoce du cancer , Tumeurs du col de l'utérus/diagnostic , Tumeurs du col de l'utérus/prévention et contrôle , Tumeurs colorectales/diagnostic , Tumeurs colorectales/prévention et contrôle , Personnel de santéRÉSUMÉ
Background: Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. Methods: We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-hour profiles of ambulatory blood pressure monitoring (ABPM) in the African American Study for Kidney Disease and Hypertension (AASK) cohort and the Chronic Renal Insufficiency Cohort (CRIC) using Cox proportional hazards models. Results: We find that rhythmic profiling of BP through JTK_Cycle analysis identifies subgroups of CRIC participants at advanced risk of cardiovascular death. CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.38, 95% CI: 1.45-7.88, p=0.005). This substantially increased risk was independent of whether ABPM followed a dipping or non-dipping pattern whereby non-dipping or reverse dipping were not significantly associated with cardiovascular death in patients with prior CVD (p>0.1). In the AASK cohort, unadjusted models demonstrate a higher risk in reaching end stage renal disease among participants without rhythmic ABPM components (HR:1.80, 95% CI: 1.10-2.96); however, full adjustment abolished this association. Conclusions: This study proposes rhythmic blood pressure components as a novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.
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BACKGROUND: The growing amount of high dimensional biomolecular data has spawned new statistical and computational models for risk prediction and disease classification. Yet, many of these methods do not yield biologically interpretable models, despite offering high classification accuracy. An exception, the top-scoring pair (TSP) algorithm derives parameter-free, biologically interpretable single pair decision rules that are accurate and robust in disease classification. However, standard TSP methods do not accommodate covariates that could heavily influence feature selection for the top-scoring pair. Herein, we propose a covariate-adjusted TSP method, which uses residuals from a regression of features on the covariates for identifying top scoring pairs. We conduct simulations and a data application to investigate our method, and compare it to existing classifiers, LASSO and random forests. RESULTS: Our simulations found that features that were highly correlated with clinical variables had high likelihood of being selected as top scoring pairs in the standard TSP setting. However, through residualization, our covariate-adjusted TSP was able to identify new top scoring pairs, that were largely uncorrelated with clinical variables. In the data application, using patients with diabetes (n = 977) selected for metabolomic profiling in the Chronic Renal Insufficiency Cohort (CRIC) study, the standard TSP algorithm identified (valine-betaine, dimethyl-arg) as the top-scoring metabolite pair for classifying diabetic kidney disease (DKD) severity, whereas the covariate-adjusted TSP method identified the pair (pipazethate, octaethylene glycol) as top-scoring. Valine-betaine and dimethyl-arg had, respectively, ≥ 0.4 absolute correlation with urine albumin and serum creatinine, known prognosticators of DKD. Thus without covariate-adjustment the top-scoring pair largely reflected known markers of disease severity, whereas covariate-adjusted TSP uncovered features liberated from confounding, and identified independent prognostic markers of DKD severity. Furthermore, TSP-based methods achieved competitive classification accuracy in DKD to LASSO and random forests, while providing more parsimonious models. CONCLUSIONS: We extended TSP-based methods to account for covariates, via a simple, easy to implement residualizing process. Our covariate-adjusted TSP method identified metabolite features, uncorrelated from clinical covariates, that discriminate DKD severity stage based on the relative ordering between two features, and thus provide insights into future studies on the order reversals in early vs advanced disease states.
Sujet(s)
Diabète , Néphropathies diabétiques , Insuffisance rénale chronique , Humains , Néphropathies diabétiques/diagnostic , Bétaïne , Algorithmes , Métabolomique/méthodesRÉSUMÉ
Background: Elevated urine albumin to creatinine ratio (UACR) is associated with cerebrovascular disease and cognitive impairment in older adults, though few studies have evaluated these relationships in midlife. This is particularly important to assess in American Indian populations, which are disproportionately impacted by diabetes and kidney disease. Additionally, evidence suggests that biomarkers may perform differently in underrepresented groups, thus, it is crucial to validate biomarkers in this unique population. Methods: Twenty-five participants from the Zuni Pueblo underwent neuropsychological assessment and an MRI that included fluid attenuated inversion recovery (FLAIR) and diffusion imaging to calculate recently developed MRI markers of cerebrovascular small vessel disease (Peak width of Skeletonized Mean Diffusivity (PSMD), mean free-water fraction (mFW), white matter hyperintensity (WMH)). Results: Regression analyses indicated no significant associations between UACR, MRI biomarkers and cognitive outcomes. Analyses of covariance indicated that the Zuni Indian cohort exhibited reduced white matter damage relative to an existing cohort of older adults with vascular cognitive impairment when accounting for age, sex, and education. Slower processing speed was associated with greater white matter disease across all measures examined. Conclusions: Our pilot study validated the use of MRI biomarkers of cerebrovascular disease in this unique cohort of American Indians.
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BACKGROUND: When a Zuni elder sustains a fall-related injury, the closest tribal skilled nursing facility is 100 miles from the Pueblo and no physical therapy services are available. Thus, fall prevention strategies as a primary intervention to avert injurious falls and preserve aging in place are needed. The objective of the study is to compare the effectiveness of a community health representative (CHR)-delivered, culturally-adapted Otago Exercise Program (OEP) fall prevention program compared to the standard of care education-based fall risk management. METHODS: "Standing Strong in Tribal Communities: Assessing Elder Falls Disparity" is mixed-methods research with a randomized controlled trial. The CHRs will be trained to deliver the culturally-adapted OEP trial and offer advantages of speaking "Shiwi" (Zuni tribal language) and understanding Zuni traditions, family structures, and elders' preferences for receiving health information. Focus groups will be conducted to assure all materials are culturally appropriate, and adapted. A physical therapist will train CHRs to screen elders for falls risk and to deliver the OEP to the intervention group and education to the control group. Up to 400 Zuni elders will be screened by the CHRs for falls risk and 200 elders will be enrolled into the study (1:1 random allocation by household). The intervention is 6 months with measurements at baseline, 3, 6 and 12 months. The primary outcome is improved strength and balance (timed up and go, sit to stand and 4 stage balance test), secondary outcomes include falls incidence, self-efficacy using Attitudes to Falls-Related Interventions Scale, Medical Outcomes Study Short Form 12 (SF-12v2) and Self-Efficacy for Managing Daily Activities. DISCUSSION: Fall prevention for Zuni elders was identified as a tribal priority and this trial is built upon longstanding collaborations between the investigative team, Zuni tribal leaders, and multiple tribal health programs. Delivery by the CHRs make this model more acceptable, and thus, more sustainable long term. This study has the potential to change best practice for elder care in tribal and rural areas with limited access to physical therapist-delivered fall prevention interventions and aligns with tribal goals to avert fall-related injury, reduce healthcare disparity, and preserve elder's independence. TRIAL REGISTRATION: NCT04876729.
Sujet(s)
Traitement par les exercices physiques , Équilibre postural , Sujet âgé , Traitement par les exercices physiques/méthodes , Humains , Vie autonome , LangageRÉSUMÉ
American Indians (AIs) in New Mexico have lower cancer screening rates compared to other populations and are more likely to be diagnosed with cancer at an advanced stage of the disease as reported by Li et al. (Archives of Internal Medicine 163(1):49-56, 2003). AIs also have the lowest 5-year cancer survival rates compared to any ethnic/racial group in the USA as reported by Clegg et al. (Arch Intern Med 162:1985-1993, 2002) and Edwards et al. (Cancer 97:1407-1427, 2005). Numerous barriers such as cultural beliefs, fear, fatalism, mistrust, stigma, and lack of culturally appropriate interventions could contribute to low cancer screening rates as reported by Daley et al. (J Health Dispar Res Pract 5(2), 2012); Filippi et al. (J Prim Care Community Health 4(3):160-166, 2013); James et al. (Prev Chronic Dis 10:E170, 2013); and Schumacher et al. (Cancer Causes Control 19(7):725-737, 2008). Trained Community Health Representatives (CHRs) from the Zuni Pueblo and native Zuni undergraduate students led six 1-h focus group sessions using a structured focus group guide with probes. The focus groups were conducted among 51 participants from different age groups (20-29 years, n = 19; 30-49 years, n = 17; and 50 years and older, n = 15) stratified by sex. Focus groups were conducted in both English and Shiwi (Zuni) languages. Sessions were audio recorded, and team members took notes. CHRs transcribed the notes and audio recordings, and created a codebook for qualitative data analysis. In the focus groups, participants provided Zuni-specific cultural context, opinion, and experience regarding (1) general knowledge about cancer, (2) cancer risk, (3) cancer risk reduction, (4) personal experiences with cancer, and (5) culturally competent delivery of cancer information and resources. Understanding the perceptions of cancer within the Zuni Pueblo is an essential component in the development of interventional/preventative measures and improvement of current care. Ultimately, this information will provide a basis for the next steps in culturally sensitive cancer care for the Zuni Pueblo.
Sujet(s)
Indiens d'Amérique Nord , Tumeurs , Humains , Jeune adulte , Adulte , Langage , Tumeurs/diagnostic , Tumeurs/prévention et contrôle , Groupes de discussion , Population d'origine amérindienneRÉSUMÉ
BACKGROUND: Health systems and providers across America are increasingly employing telehealth technologies to better serve medically underserved low-income, minority, and rural populations at the highest risk for health disparities. The Patient-Centered Outcomes Research Institute (PCORI) has invested US $386 million in comparative effectiveness research in telehealth, yet little is known about the key early lessons garnered from this research regarding the best practices in using telehealth to address disparities. OBJECTIVE: This paper describes preliminary lessons from the body of research using study findings and case studies drawn from PCORI seminal patient-centered outcomes research (PCOR) initiatives. The primary purpose was to identify common barriers and facilitators to implementing telehealth technologies in populations at risk for disparities. METHODS: A systematic scoping review of telehealth studies addressing disparities was performed. It was guided by the Arksey and O'Malley Scoping Review Framework and focused on PCORI's active portfolio of telehealth studies and key PCOR identified by study investigators. We drew on this broad literature using illustrative examples from early PCOR experience and published literature to assess barriers and facilitators to implementing telehealth in populations at risk for disparities, using the active implementation framework to extract data. Major themes regarding how telehealth interventions can overcome barriers to telehealth adoption and implementation were identified through this review using an iterative Delphi process to achieve consensus among the PCORI investigators participating in the study. RESULTS: PCORI has funded 89 comparative effectiveness studies in telehealth, of which 41 assessed the use of telehealth to improve outcomes for populations at risk for health disparities. These 41 studies employed various overlapping modalities including mobile devices (29/41, 71%), web-based interventions (30/41, 73%), real-time videoconferencing (15/41, 37%), remote patient monitoring (8/41, 20%), and store-and-forward (ie, asynchronous electronic transmission) interventions (4/41, 10%). The studies targeted one or more of PCORI's priority populations, including racial and ethnic minorities (31/41, 41%), people living in rural areas, and those with low income/low socioeconomic status, low health literacy, or disabilities. Major themes identified across these studies included the importance of patient-centered design, cultural tailoring of telehealth solutions, delivering telehealth through trusted intermediaries, partnering with payers to expand telehealth reimbursement, and ensuring confidential sharing of private information. CONCLUSIONS: Early PCOR evidence suggests that the most effective health system- and provider-level telehealth implementation solutions to address disparities employ patient-centered and culturally tailored telehealth solutions whose development is actively guided by the patients themselves to meet the needs of specific communities and populations. Further, this evidence shows that the best practices in telehealth implementation include delivery of telehealth through trusted intermediaries, close partnership with payers to facilitate reimbursement and sustainability, and safeguards to ensure patient-guided confidential sharing of personal health information.
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Minorités ethniques et raciales , Télémédecine , Recherche comparative sur l'efficacité , Humains , Évaluation des résultats des patients , PauvretéRÉSUMÉ
BACKGROUND: Converting electronic health record (EHR) entries to useful clinical inferences requires one to address the poor scalability of existing implementations of Generalized Linear Mixed Models (GLMM) for repeated measures. The major computational bottleneck concerns the numerical evaluation of multivariable integrals, which even for the simplest EHR analyses may involve millions of dimensions (one for each patient). The hierarchical likelihood (h-lik) approach to GLMMs is a methodologically rigorous framework for the estimation of GLMMs that is based on the Laplace Approximation (LA), which replaces integration with numerical optimization, and thus scales very well with dimensionality. METHODS: We present a high-performance, direct implementation of the h-lik for GLMMs in the R package TMB. Using this approach, we examined the relation of repeated serum potassium measurements and survival in the Cerner Real World Data (CRWD) EHR database. Analyzing this data requires the evaluation of an integral in over 3 million dimensions, putting this problem beyond the reach of conventional approaches. We also assessed the scalability and accuracy of LA in smaller samples of 1 and 10% size of the full dataset that were analyzed via the a) original, interconnected Generalized Linear Models (iGLM), approach to h-lik, b) Adaptive Gaussian Hermite (AGH) and c) the gold standard for multivariate integration Markov Chain Monte Carlo (MCMC). RESULTS: Random effects estimates generated by the LA were within 10% of the values obtained by the iGLMs, AGH and MCMC techniques. The H-lik approach was 4-30 times faster than AGH and nearly 800 times faster than MCMC. The major clinical inferences in this problem are the establishment of the non-linear relationship between the potassium level and the risk of mortality, as well as estimates of the individual and health care facility sources of variations for mortality risk in CRWD. CONCLUSIONS: We found that the direct implementation of the h-lik offers a computationally efficient, numerically accurate approach for the analysis of extremely large, real world repeated measures data via the h-lik approach to GLMMs. The clinical inference from our analysis may guide choices of treatment thresholds for treating potassium disorders in the clinic.
Sujet(s)
Dossiers médicaux électroniques , Potassium , Théorème de Bayes , Humains , Modèles linéaires , Chaines de Markov , Méthode de Monte Carlo , Valeurs de référenceRÉSUMÉ
BACKGROUND: Home-Based Kidney Care (HBKC) is a pragmatic treatment approach that addresses patient preferences and cultural barriers to healthcare. We previously reported the results of a clinical trial of HBKC vs. usual care in a cohort of Zuni Indians in New Mexico. This study investigated the potential for differential efficacy of HBKC vs. usual care according to type 2 diabetes (T2DM) status. METHODS: We analyzed the data from all individuals who participated in a randomized clinical trial that compared HBKC to usual care among patients with CKD, and assessed whether the effect of the HBKC intervention affected the subset of patients with T2DM differently than those individuals without T2DM. We used linear regression models to estimate the effect of HBKC on improvement in Patient Activation Measure (PAM) total scores within the groups of participants defined by T2DM status, and to compare the effects between these two groups. We used generalized estimating equations (GEE) to account for household clustering. RESULTS: The original study enrolled 63 participants into the HBKC group, and 62 into the usual care. Ninety-eight of these individuals completed the 12-month intervention, 50 in the HBKC group and 48 in the usual care group. The present study compared the intervention effect in the 56 participants with T2DM (24 participants in the HBKC group and 32 in usual care) to the intervention effect in the 42 participants without T2DM (26 participants in the HBKC group and 16 in usual care). Those with T2DM who received the HBKC intervention experienced an average increase in PAM total scores of 16.0 points (95% Confidence Interval: 8.8-23.1) more than those with T2DM who were in the usual care group. For those without T2DM, the intervention had essentially no effect, with those who received the HBKC intervention having an average PAM total scores that was 1.4 points (95% C.I.: -12.4 to 9.6) lower than those who received usual care. There was a significantly different HBKC treatment effect by T2DM status (pâ¯=â¯0.02). CONCLUSION: This secondary analysis suggests that the effectiveness of this HBKC intervention on increasing patient activation is most notable among those CKD patients who also have T2DM.
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Diabète de type 2 , Insuffisance rénale chronique , Diabète de type 2/complications , Diabète de type 2/ethnologie , Diabète de type 2/thérapie , Services de soins à domicile , Humains , Indiens d'Amérique Nord , Rein , Nouveau Mexique , Participation des patients , Insuffisance rénale chronique/ethnologie , Insuffisance rénale chronique/thérapieRÉSUMÉ
BACKGROUND: Chronic kidney disease (CKD) is an increasing epidemic globally that is associated with adverse health outcomes including end stage kidney disease (ESKD), cardiovascular disease (CVD), and death. American Indians (AIs) have a higher prevalence of CKD than most other racial/ethnic groups, due in part to a high prevalence of type 2 diabetes. Other genetic and environmental factors not yet identified may also contribute to the disproportionate burden of CKD in AIs. METHOD: We will establish 3 clinical centers to recruit AIs from the Southwest United States (US) to expand the Chronic Renal Insufficiency Cohort (CRIC) study. We will follow the current CRIC protocol for kidney and cardiovascular measures and outcomes, which include ambulatory monitoring of kidney function and the use of mobile health technologies for CVD sub-phenotyping, and compare the outcomes in AIs with those in other racial/ethnic groups in CRIC. DISCUSSION: AI-CRIC will identify the role of various risk factors for rapid loss of kidney function among AIs of the Southwest US. In addition, to better understand the natural history of CKD and CVD in this high-risk population, we will identify unique risk factors for CKD and CVD progression in AIs. We will also compare event rates and risk factors for kidney and cardiovascular events in AIs with the other populations represented in CRIC.
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Indiens d'Amérique Nord , Insuffisance rénale chronique/ethnologie , Maladies cardiovasculaires/épidémiologie , Maladies cardiovasculaires/ethnologie , Maladies cardiovasculaires/physiopathologie , Études de cohortes , Diabète de type 2/épidémiologie , Diabète de type 2/ethnologie , Diabète de type 2/métabolisme , Diabète de type 2/physiopathologie , Humains , Insuffisance rénale chronique/épidémiologie , Insuffisance rénale chronique/métabolisme , Insuffisance rénale chronique/physiopathologie , Facteurs de risque , États du Sud-Ouest des États-Unis/épidémiologieRÉSUMÉ
PURPOSE: To evaluate the influence of single nucleotide polymorphisms (SNPs) of CYP19A1 on the response and susceptibility to side effects from testosterone therapy. This is a prospective, single-arm study of men with low-morning serum testosterone (<10.68 nmol/l) administered testosterone cypionate 200 mg intramuscularly every 2 weeks for 18 months. METHODS: We measured areal bone mineral density (aBMD) and body composition by dual energy X-ray absorptiometry, tibial volumetric BMD and geometry by peripheral quantitative computer tomography, bone turnover markers by enzyme-linked immunosorbent assay, testosterone, and estradiol by liquid-chromatography/mass-spectroscopy, genotyping by microarray, CYP19A1 expression by quantitative polymerase chain reaction, hematocrit and prostate-specific antigen (PSA). RESULTS: We enrolled 105 men (40-74-years-old). SNPs rs1062033 and rs700518 were associated with significant differences in outcomes at 18 months. The GG genotype in rs1062033 had significant increase in whole body aBMD, but had significant decrease in tibial bone size compared to the CG and CC genotypes. Body composition analysis showed that the CC genotype of rs1062033, and the AA genotype of rs700518, had significant increase in total lean and appendicular lean mass compared to CG and GG, and AG and GG, respectively. The GG genotype of rs700518 had significant increase in PSA (GG = 105.8 ± 23.3% vs. AG + AA = 53.4 ± 11.3%, p = 0.046) while hematocrit changes were comparable among genotypes. CYP19A1 expression was highest in GG genotype in both SNPs. CONCLUSIONS: For the first time, we demonstrated that CYP19A1 SNPs influence response to testosterone therapy in hypogonadal men, highlighting the importance of genetic profiling in therapeutics even for common clinical conditions.
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Aromatase/génétique , Composition corporelle/génétique , Os et tissu osseux/métabolisme , Testostérone/déficit , Testostérone/usage thérapeutique , Absorptiométrie photonique , Adulte , Sujet âgé , Indice de masse corporelle , Densité osseuse/effets des médicaments et des substances chimiques , Remodelage osseux/effets des médicaments et des substances chimiques , Humains , Mâle , Adulte d'âge moyen , Appareil locomoteur/effets des médicaments et des substances chimiques , Appareil locomoteur/métabolisme , Polymorphisme génétique/génétique , Polymorphisme de nucléotide simple/génétique , Études prospectives , Prostate/imagerie diagnostique , Prostate/effets des médicaments et des substances chimiques , Antigène spécifique de la prostate/sang , Testostérone/effets indésirablesRÉSUMÉ
OBJECTIVE: Administration of excess chloride in 0.9% normal saline (NS) decreases renal perfusion and glomerular filtration rate, thereby increasing the risk for acute kidney injury (AKI). In this study, the effect of NS versus Isolyte use during cardiac surgery on urinary levels of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 [TIMP-2]â¯×â¯[IGFBP7] and postoperative risk of AKI were examined. DESIGN: Prospective, randomized, and single-blinded trial. SETTING: Single university medical center. PARTICIPANTS: Thirty patients over 18 years without chronic renal insufficiency or recent AKI undergoing elective cardiac surgery. INTERVENTIONS: Subjects were randomized to receive either NS or Isolyte during the intraoperative period. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in urinary levels of [TIMP2]â¯×â¯[IGFBP7] from before surgery to 24 hours postoperatively. Secondary outcomes included serum creatinine pre- and postoperatively at 24 and 48 hours, serum chloride pre- and postoperatively at 24 and 48 hours, need for dialysis prior to discharge, and arterial pH measured 24 hours postoperatively. Sixteen patients received NS and 14 patients received Isolyte. Three patients developed AKI within the first 3 postoperative days, all in the NS group. The authors found increases in [TIMP-2]â¯×â¯[IGFBP7] in both groups. However, the difference in this increase between study arms was not significant (pâ¯=â¯0.92; -0.097 to 0.107). CONCLUSION: The authors observed no change in urinary [TIMP-]â¯×â¯[IGFBP7] levels in patients receiving NS versus Isolyte during cardiac surgery. Future larger studies in patients at higher risk for AKI are recommended to evaluate the impact of high- versus lower-chloride solutions on the risk of postoperative AKI after cardiac surgery.
Sujet(s)
Atteinte rénale aigüe/prévention et contrôle , Procédures de chirurgie cardiaque/effets indésirables , Débit de filtration glomérulaire/physiologie , Protéines de liaison aux IGF/urine , Solution de Ringer au lactate/administration et posologie , Solution physiologique salée/administration et posologie , Inhibiteur tissulaire de métalloprotéinase-2/urine , Atteinte rénale aigüe/étiologie , Atteinte rénale aigüe/urine , Sujet âgé , Marqueurs biologiques/urine , Femelle , Études de suivi , Humains , Perfusions veineuses , Mâle , Adulte d'âge moyen , Complications postopératoires/étiologie , Complications postopératoires/prévention et contrôle , Complications postopératoires/urine , Études prospectives , Courbe ROC , Méthode en simple aveugleRÉSUMÉ
BACKGROUND AND OBJECTIVES: The burden of CKD is greater in ethnic and racial minorities and persons living in rural communities, where access to care is limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 12-month clinical trial was performed in 98 rural adult Zuni Indians with CKD to examine the efficacy of a home-based kidney care program. Participants were randomized by household to receive usual care or home-based care. After initial lifestyle coaching, the intervention group received frequent additional reinforcement by community health representatives about adherence to medicines, diet and exercise, self-monitoring, and coping strategies for living with stress. The primary outcome was change in patient activation score, which assesses a participant's knowledge, skill, and confidence in managing his/her own health and health care. RESULTS: Of 125 randomized individuals (63 intervention and 62 usual care), 98 (78%; 50 intervention and 48 usual care) completed the 12-month study. The average patient activation score after 12 months was 8.7 (95% confidence interval, 1.9 to 15.5) points higher in the intervention group than in the usual care group after adjusting for baseline score using linear models with generalized estimating equations. Participants randomized to the intervention had 4.8 (95% confidence interval, 1.4 to 16.7) times the odds of having a final activation level of at least three ("taking action") than those in the usual care group. Body mass index declined by 1.1 kg/m2 (P=0.01), hemoglobin A1c declined by 0.7% (P=0.01), high-sensitivity C-reactive protein declined by 3.3-fold (P<0.001), and the Short-Form 12 Health Survey mental score increased by five points (P=0.002) in the intervention group relative to usual care. CONCLUSIONS: A home-based intervention improves participants' activation in their own health and health care, and it may reduce risk factors for CKD in a rural disadvantaged population.
Sujet(s)
Services de soins à domicile , Indiens d'Amérique Nord , Défaillance rénale chronique/thérapie , Participation des patients , Évolution de la maladie , Femelle , Humains , Défaillance rénale chronique/épidémiologie , Mâle , Adulte d'âge moyen , Facteurs de risque , Résultat thérapeutiqueRÉSUMÉ
Background: Reliance on natural resources brings Native American communities into frequent contact with environmental media, which, if contaminated, represents an exposure route for environmental pollutants. Native American communities vary in their perspectives on research and relatively little is known about the range of perspectives regarding the use of biological samples for environmental exposure assessment. Methods: Thirty-one members of Zuni Pueblo (median age = 40.0 years, range = 26â»59 years) participated a series of four focus groups. Qualitative themes emerging from the focus group discussion transcripts were identified by content analysis. Results: Emergent themes included adequate informed consent, traditional beliefs, and personal choice. Conclusions: The discussions reinforced the central role of traditional values in the decision to participate in research involving biological samples for environmental exposure assessment. Decision-making required a balance between the perceived value of the proposed project and its purpose, with cultural perspectives surrounding the biological sample requested. We examine the potential for study bias and include recommendations to aid in the collaborative identification and control of unintended risks posed by the use of biological samples in environmental health studies in native communities.
Sujet(s)
Caractéristiques culturelles , Santé environnementale , Surveillance de l'environnement/méthodes , Indiens d'Amérique Nord/psychologie , Adulte , Prise de décision , Exposition environnementale/analyse , Femelle , Groupes de discussion , Humains , Consentement libre et éclairé , Mâle , Adulte d'âge moyenRÉSUMÉ
BACKGROUND: The unintentional death rate from falls is higher among American Indians from the US Southwest than from other regions in the country. The Zuni Pueblo is a geographically isolated, rural American Indian community located in western New Mexico. Education and screening for falls risk is lacking in this community and may be needed to reduce falls and falls-related illness and death. COMMUNITY CONTEXT: Building on a 17-year relationship with the Zuni Health Initiative, meetings were held with Zuni tribal leadership, staff from the Zuni Senior Center and Zuni Home Health Services, members of the Zuni Comprehensive Community Health Center, Indian Health Service, and Zuni community health representatives (CHRs) to discuss elder falls in the community. Existing infrastructure, including CHRs who were already trained and certified in diabetes education and prevention, provided support for the study. METHODS: Tribal leadership agreed that CHRs would be trained to administer the Centers for Disease Control and Prevention's (CDC's) Stay Independent checklist to assess falls risk. They administered the checklist during one-on-one interviews in Shiwi (Zuni native language), English, or both to a convenience sample of 50 Zuni elders. OUTCOMES: Mean age of participants was 72 (standard deviation, 7.4) years, and 78% were women. Fifty-two percent reported at least 1 fall during the past year; 66% scored 4 or more on the CDC Stay Independent checklist, indicating elevated risk for falls. CHRs reported that the checklist was easy to administer and culturally accepted by the elder participants. INTERPRETATION: This study broadened the Zuni Health Initiative to include falls risk screening. Self-reported falls were common in this small sample, and the incidence was significantly higher than the national rate. These results highlight the need for community engagement, using culturally acceptable falls screening, to promote falls education and implement falls prevention programs.