Spokane, WA, United States
Spokane, WA, United States

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Anderberg R.J.,Providence Medical Research Center | Anderberg R.J.,Childrens Hospital | Meek R.L.,Providence Medical Research Center | Hudkins K.L.,University of Washington | And 5 more authors.
Laboratory Investigation | Year: 2015

Inflammatory pathways are central mechanisms in diabetic kidney disease (DKD). Serum amyloid A (SAA) is increased by chronic inflammation, but SAA has not been previously evaluated as a potential DKD mediator. The aims of this study were to determine whether SAA is increased in human DKD and corresponding mouse models and to assess effects of SAA on podocyte inflammatory responses. SAA was increased in the plasma of people with DKD characterized by overt proteinuria and inversely correlated with estimated glomerular filtration rate (creatinine-based CKD-EPI). SAA was also elevated in plasma of diabetic mouse models including type 1 diabetes (streptozotocin/C57BL/6) and type 2 diabetes (BTBR-ob/ob). SAA mRNA (Nephromine) was increased in human DKD compared with non-diabetic and/or glomerular disease controls (glomerular fold change 1.5, P=0.017; tubulointerstitium fold change 1.4, P=0.021). The kidneys of both diabetic mouse models also demonstrated increased SAA mRNA (quantitative real-time PCR) expression compared with non-diabetic controls (type 1 diabetes fold change 2.9; type 2 diabetes fold change 42.5, P=0.009; interaction by model P=0.57). Humans with DKD and the diabetic mouse models exhibited extensive SAA protein deposition in the glomeruli and tubulointerstitium in similar patterns by immunohistochemistry. SAA localized within podocytes of diabetic mice. Podocytes exposed to advanced glycation end products, metabolic mediators of inflammation in diabetes, increased expression of SAA mRNA (fold change 15.3, P=0.004) and protein (fold change 38.4, P=0.014). Podocytes exposed to exogenous SAA increased NF-κB activity, and pathway array analysis revealed upregulation of mRNA for NF-κB-dependent targets comprising numerous inflammatory mediators, including SAA itself (fold change 17.0, P=0.006). Inhibition of NF-κB reduced these pro-inflammatory responses. In conclusion, SAA is increased in the blood and produced in the kidneys of people with DKD and corresponding diabetic mouse models. Podocytes are likely to be key responder cells to SAA-induced inflammation in the diabetic kidney. SAA is a compelling candidate for DKD therapeutic and biomarker discovery. © 2015 USCAP, Inc.


PubMed | Providence Medical Research Center, University of Washington, Washington State University and Care Network
Type: Journal Article | Journal: Journal of managed care & specialty pharmacy | Year: 2016

Manufacturer prescription assistance programs (PAPs) have been developed to provide medications at little or no cost to eligible patients. There are over 200 PAPs available from pharmaceutical companies, and each may have different eligibility requirements and assistance guidelines. A formalized community-based patient prescription coordinator can help patients navigate these programs by reviewing an applicants financial information and medication requirements to identify which PAPs are most appropriate. Little is known, however, about whether providing such guidance is associated with a reduction in acute care utilization.To evaluate changes in emergency department and hospital utilization among patients who received care coordination and financial assistance with prescribed medications.This single-cohort interrupted time-series study included participants in eastern Washington state who enrolled in the Spokane Prescription Assistance Network (SPAN) program between March 1, 2009, and August 31, 2012. Referrals to the SPAN patient prescription coordinator were made by a social service agency or medical provider for patients who may have difficulty paying for prescribed medications. Initial patient contact occurred while the patient was still being treated in a clinic or hospital or through a direct visit to the coordinators community-based office. Participants were contacted 6 months after the initial appointment and then annually thereafter to review current medications and health status. A review of electronic health records provided information on hospitalizations and emergency department visits in the 12 months before and after program entry.Among SPAN participants (n = 310), emergency department and hospital encounters declined from 0.38 per participant in the year before enrollment to 0.20 encounters in the year following program entry. A repeated-measures mixed-effects model indicated SPAN participation was associated with a 51% decline in the rate of emergency department and hospital utilization (incidence rate ratio [IRR] = 0.49; 95% CI = 0.31-0.77; P = 0.002). Observed effects differed by prescription class. Factor interactions revealed significant reductions in utilization for participants with prescribed pulmonary medications (IRR = 0.58; 95% CI = 0.37-0.92; P = 0.019). Assistance with mental health (psychotropic) medications was associated with increased incidence of utilization (IRR = 2.07; 95% CI = 1.32-3.24; P = 0.001). At the time of SPAN enrollment, 60% of participants had prescriptions for psychotropic medications.A formalized patient prescription coordinator can help patients access prescribed medications at low cost and remain compliant with treatment plans. In a study of a coordination pilot program, reductions in hospital admissions and emergency department visits were observed following program participation.This study was not supported by any outside funding. The authors declare no conflicts of interest. Study design was created by Burley, McPherson, and Daratha. Burley Daratha, Selinger, and Armstrong collected the data, with interpretation performed by Burley, Daratha, and Tuttle, assisted by McPherson. The manuscript was written by Burley, Daratha, and Selinger, with assistance from White, and revised by Burley, White, and Selinger, with assistance from Daratha and Tuttle.


Salvatierra G.,Seattle University | Bindler R.C.,Washington State University | Corbett C.,Washington State University | Roll J.,Washington State University | And 3 more authors.
Critical Care Medicine | Year: 2014

OBJECTIVE:: To determine the relationship between implementation of rapid response teams and improved mortality rate using a large, uniform dataset from one state in the United States. DESIGN:: This observational cohort study included 471,062 adult patients hospitalized between 2001 and 2009. SETTING:: Ten acute tertiary care hospitals in Washington State. PATIENTS OR OTHER PARTICIPANTS:: Hospital abstract records on adult patients (18 years old or older) were examined (n = 471,062). Patients most likely to benefit from rapid response team interventions were included and other prognostic factors of severity of illness and comorbidities were controlled. Each participating hospital provided the implementation date of their rapid response team intervention. Mortality rates in 31 months before rapid response team implementation (pre-rapid response team time period) were compared with mortality rates in 31 months following rapid response team implementation (post-rapid response team time period). INTERVENTION(S):: Implementation of a rapid response team within each acute tertiary care hospital. MEASUREMENTS AND MAIN RESULTS:: In-hospital mortality. Relative risk for in-hospital mortality improved in the post-rapid response team time period compared with the pre-rapid response team time period (relative risk = 0.76; 95% CI = 0.72-0.80; p < 0.001). CONCLUSIONS:: In-hospital mortality improved in six of 10 acute tertiary care hospitals in the post-rapid response team time period when compared with the pre-rapid response team time period. Because of a long-term trend of decline in hospital mortality, these decreases could not be unambiguously attributed to rapid response team implementation. Further research should examine additional objective outcomes and optimal configuration of rapid response teams to maximize intervention effectiveness. © 2014 by the Society of Critical Care Medicine and Lippincott Williams and Wilkins.


Tuttle K.R.,Providence Medical Research Center | Tuttle K.R.,University of Washington | Milton J.E.,Providence Medical Research Center | Packard D.P.,Providence Medical Research Center | And 3 more authors.
American Journal of Kidney Diseases | Year: 2012

Background: Dietary protein has been variably reported to either lower or raise blood pressure. The purpose of this study was to determine whether intakes of specific amino acids differentially associate with blood pressure. Study Design: Observational cohort study by secondary analysis of clinical trial data. Setting & Participants: Study of low-fat versus Mediterranean-style diets in patients with prevalent cardiovascular disease. Predictor: Dietary amino acids. Outcomes: Systolic and diastolic blood pressure. Measurements: Dietary nutrients and cardiovascular risk factors were assessed at baseline, 3 and 6 months, and then every 6 months for 2 years. Results: Baseline blood pressure was 119 ± 16 (SD)/72 ± 10 (SD) mm Hg (n = 92) and dietary protein intake was 80 ± 31 g/d. Independent amino acid variables (quartiles of intake) were analyzed by generalized estimating equation models with prespecified covariates for time-varying systolic and diastolic blood pressure. The odds of each 1-SD higher systolic or diastolic blood pressure (ie, 16 and 10 mm Hg, respectively) were increased per quartile of intake for methionine (ORs of 1.29 [95% CI, 1.14-1.46] and 1.21 [95% CI, 1.05-1.39], respectively) and alanine (ORs of 1.17 [95% CI, 1.05-1.30] and 1.22 [95% CI, 1.07-1.38], respectively). Quartiles of intake for threonine (ORs of 0.84 [95% CI, 0.74-0.96] and 0.87 [95% CI, 0.75-1.01], respectively) and histidine (ORs of 0.92 [95% CI, 0.86-1.00] and 0.89 [95% CI, 0.82-0.97], respectively) had inverse associations with the same degree of difference in blood pressure. Limitations: Modest sample-size biases toward the chance of false-negative results; potential for residual confounding; colinearity between amino acids may obscure relevant relationships to blood pressure; associational findings do not establish causality. Conclusions: Intakes of methionine and alanine were associated positively with higher blood pressure, whereas intakes of threonine and histidine had inverse associations. These amino acids merit further study for advancing dietary approaches to blood pressure reduction. © 2012 National Kidney Foundation, Inc.


Chwastiak L.A.,University of Washington | Davydow D.S.,University of Washington | McKibbin C.L.,University of Wyoming | Schur E.,University of Washington | And 6 more authors.
Psychosomatics | Year: 2014

Background: Medical-surgical rehospitalizations within a month after discharge among patients with diabetes result in tremendous costs to the US health care system. Objective: The study's aim was to examine whether co-morbid serious mental illness diagnoses (bipolar disorder, schizophrenia, or other psychotic disorders) among patients with diabetes are independently associated with medical-surgical rehospitalization within a month of discharge after an initial hospitalization. Methods: This cohort study of all community hospitals in Washington state evaluated data from 82,060 adults discharged in the state of Washington with any International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis indicating diabetes mellitus between 2010 and 2011. Data on medical-surgical hospitalizations were obtained from the Washington State Comprehensive Hospital Abstract Reporting System. Co-morbid serious mental illness diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes indicating bipolar disorder, schizophrenia, or other psychotic disorders. Logistic regression analyses identified factors independently associated with rehospitalization within a month of discharge. Cox proportional hazard analyses estimated time to rehospitalization for the entire study period. Results: After adjusting for demographics, medical co-morbidity, and characteristics of the index hospitalization, co-morbid serious mental illness diagnosis was independently associated with increased odds of rehospitalization within 1 month among patients with diabetes who had a medical-surgical hospitalization (odds ratio: 1.24, 95% confidence interval: 1.07, 1.44). This increased risk of rehospitalization persisted throughout the study period (up to 24. mo). Conclusions: Co-morbid serious mental illness in patients with diabetes is independently associated with greater risk of early medical-surgical rehospitalization. Future research is needed to define and specify targets for interventions at points of care transition for this vulnerable patient population. © 2014 Academy of Psychosomatic Medicine.


Shaw M.R.,Washington State University | Daratha K.B.,Washington State University | Daratha K.B.,Providence Medical Research Center | Daratha K.B.,University of Washington | And 2 more authors.
Journal of Asthma | Year: 2013

Objectives. Asthma is one of the most common chronic conditions among children and is one of the leading causes for pediatric hospitalizations. More evidence is needed to clarify the risks of repeat hospitalization and the underlying factors contributing to adverse health outcomes among pediatric patients hospitalized with asthma. The purpose of this study was to examine the risk of subsequent hospitalizations among pediatric patients hospitalized with asthma compared to a reference cohort of children hospitalized for all other diagnoses. Methods. The Washington State (WA) Comprehensive Hospital Abstract Reporting System (CHARS) was used to obtain data for the study. Data describing 81,946 hospitalized pediatric patients admitted from 2004 to 2008 were available. The risk of subsequent hospitalization among children admitted for asthma as compared to a reference cohort was examined. Results. The asthma cohort had a 33% (HR = 1.33 [99% confidence interval (CI) 1.21-1.46]; p < .001) increased risk of subsequent hospitalization from 2004 to 2008. Children in the asthma cohort under the age of 13 years demonstrated a significant increased risk of subsequent hospitalization as compared to the age-matched reference cohort of children without asthma. Those in the asthma cohort who were 3-5 years old demonstrated the highest risk (50%) of subsequent hospitalization (HR = 1.50 [99% CI 1.23-1.83]; p < .001). Conclusions. Study results can be utilized in the development of appropriate interventions aimed at preventing and reducing hospital admissions, improving patient care, decreasing overall costs, and lessening complications among pediatric patients with asthma. © 2013 Informa Healthcare USA, Inc.


PubMed | University of Minnesota, University of Washington, Seattle Childrens Research Institute, Stanford University and 3 more.
Type: Journal Article | Journal: Clinical trials (London, England) | Year: 2016

In the context of research on medical practices, which includes comparative effectiveness research and pragmatic clinical trials, empirical studies have begun to raise questions about the extent to which institutional review boards interpretations and applications of research regulations align with patients values. To better understand the similarities and differences between these stakeholder groups, we compare and contrast two surveys: one of institutional review board professionals and one of patients, which examine views on consent for research on medical practices.We conducted online surveys of two target populations between July 2014 and March 2015. We surveyed 601 human subjects research professionals out of 1500 randomly selected from the Public Responsibility in Medicine and Research membership list (40.1% response rate), limiting analysis to 537 respondents who reported having had institutional review board experience. We also surveyed 120 adult patients out of 225 approached at subspecialty clinics in Spokane, Washington (53.3% response rate). Our survey questions probed attitudes about consent in the context of research on medical practices using medical record review and randomization. The patient survey included three embedded animated videos to explain these concepts.A majority of institutional review board professionals distinguished between consent preferences for medical record review and randomization, ranked clinicians as the least preferred person to obtain participant consent (54.6%), and viewed written or verbal permission as the minimum acceptable consent approach for research on medical practices using randomization (87.3%). In contrast, most patients had similar consent preferences for research on medical practices using randomization and medical record review, most preferred to have consent conversations with their doctors rather than with researchers for studies using randomization (72.6%) and medical record review (67.0%), and only a few preferred to see research involving randomization (16.8%) or medical record review (13.8%) not take place if obtaining written or verbal permission would make the research too difficult to conduct. Limitations of our post hoc analysis include differences in framing, structure, and language between the two surveys and possible response bias.Our findings highlight a need to identify appropriate ways to integrate patient preferences into prevailing regulatory interpretations as institutional review boards increasingly apply research regulations in the context of research on medical practices. Dialogue between institutional review boards and research participants will be an important part of this process and should inform future regulatory guidance.


Afkarian M.,University of Washington | Sachs M.C.,University of Washington | Kestenbaum B.,University of Washington | Hirsch I.B.,University of Washington | And 4 more authors.
Journal of the American Society of Nephrology | Year: 2013

Type 2 diabetes associates with increased risk of mortality, but how kidney disease contributes to this mortality risk among individuals with type 2 diabetes is not completely understood.Here, we examined 10-year cumulative mortality by diabetes and kidney disease status for 15,046 participants in the Third National Health and Nutrition Examination Survey (NHANES III) by linking baseline data from NHANES III with the National Death Index. Kidney disease, defined as urinary albumin/creatinine ratio ≥30 mg/g and/or estimated GFR ≤60 ml/min per 1.73 m2, was present in 9.4% and 42.3% of individuals without and with type 2 diabetes, respectively. Among people without diabetes or kidney disease (reference group), 10-year cumulative all-causemortality was 7.7% (95%confidence interval [95%CI], 7.0%-8.3%), standardized to population age, sex, and race. Among individuals with diabetes but without kidney disease, standardized mortality was 11.5% (95% CI, 7.9%-15.2%), representing an absolute risk difference with the reference group of 3.9% (95% CI, 0.1%-7.7%), adjusted for demographics, and 3.4% (95% CI, 20.3% to 7.0%) when further adjusted for smoking, BP, and cholesterol. Among individuals with both diabetes and kidney disease, standardized mortality was 31.1% (95% CI, 24.7%-37.5%), representing an absolute risk difference with the reference group of 23.4% (95% CI, 17.0%-29.9%), adjusted for demographics, and 23.4% (95% CI, 17.2%-29.6%) when further adjusted. We observed similar patterns for cardiovascular and noncardiovascular mortality. In conclusion, those with kidney disease predominantly account for the increased mortality observed in type 2 diabetes. Copyright © 2013 by the American Society of Nephrology.


Alicic R.Z.,University of Washington | Alicic R.Z.,Providence Sacred Heart Medical Center and Childrens Hospital | Alicic R.Z.,Providence Medical Research Center | Patakoti R.,University of Washington | And 5 more authors.
Advances in Chronic Kidney Disease | Year: 2013

Over the last few decades, much of the world has experienced an epidemic of obesity. In the year 2008, 1.4 billion people worldwide were overweight, and 500 million were obese. Even more alarming is a fact that in the year 2010, 40 million children under the age of 5 years were overweight or obese. In the same time period, the incidence of CKD has also increased worldwide. Obesity has been recognized as a driving force of another global epidemic-diabetes, the leading cause of ESRD. Recent studies are confirming that in addition to risk associated with diabetes per se, increased body mass index is independently linked to increased risk for various kidney disorders, prominently CKD, but also renal cell carcinoma and nephrolithiasis. The purpose of this article is to review current knowledge regarding adverse effects of obesity on the kidney. © 2013 National Kidney Foundation, Inc.


Meek R.L.,Providence Medical Research Center | LeBoeuf R.C.,University of Washington | Saha S.A.,Providence Medical Research Center | Saha S.A.,University of Washington | And 6 more authors.
Nephrology Dialysis Transplantation | Year: 2013

Background. Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of highprotein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo. Methods. Mouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold >control); (iii) high glucose (HG, 30.5 mM); (iv) AA/HG combination; (v) AGEbovine serum albumin (AGE-BSA, 300 μg/mL); (vi) BSA (300 μg/mL). RAGE was inhibited by blocking antibody. Diabetic (streptozotocin) and nondiabetic mice (C57BL/6J) consumed diets with protein calories of 20 or 40% (high) for 20 weeks. People with DKD and controls provided 24-h urine samples. Results. In podocytes and mesangial cells, apoptosis (caspase 3/7 activity and TUNEL) increased in all metabolic stressor conditions. Both inflammatory mediator expression (real-time reverse transcriptase-polymerase chain reaction: serum amyloid A, caspase-4, inducible nitric oxide synthase, and monocyte chemotactic protein-1) and RAGE (immunostaining) also increased. RAGE inhibition prevented apoptosis and inflammation in podocytes. Among mice fed high protein, podocyte number (WT-1 immunostaining) decreased in the diabetic group, and only these diabetic mice developed albuminuria. Protein intake (urea nitrogen) correlated with AGE excretion (carboxymethyllysine) in people with DKD and controls. Conclusions. High-protein diet and/or diabetes-like conditions increased glomerular cell death and inflammation, responses mediated by RAGEs in podocytes. The concept that high-protein diets exacerbate early indicators of DKD is supported by data from mice and people. © The Author 2013.

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