Publications by authors named "Jingrong Yang"

34 Publications

Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study.

J Am Soc Nephrol 2021 Sep 18;32(9):2303-2314. Epub 2021 Jun 18.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: Little population-based data exist about adults with primary nephrotic syndrome.

Methods: To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression.

Results: We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death.

Conclusions: Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.
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http://dx.doi.org/10.1681/ASN.2020111583DOI Listing
September 2021

Effect of silver diamine fluoride on hyperplastic gingivitis in an adult with intellectual disability-A case report.

Spec Care Dentist 2021 Jul 22. Epub 2021 Jul 22.

National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore.

Silver diamine fluoride 38% (SDF) may possess therapeutic effects beyond desensitization, caries prevention and arresting. We report the case of a 41-year-old male with intellectual disability. He had generalized gingivitis on a reduced periodontium and presented with enlarged gingiva with mobile teeth, particularly on the upper anterior and upper left. The inflammation could not be fully resolved despite multiple debridement treatments. Due to prevalent demineralization and hypersensitive teeth on the upper left area, SDF was applied. This not only reduced the perceived hypersensitivity, but significantly improved his periodontal condition and tooth mobility over the applied areas. We discuss the potential of SDF beyond its current use.
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http://dx.doi.org/10.1111/scd.12633DOI Listing
July 2021

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Clin Kidney J 2020 Feb 20;13(1):55-62. Epub 2019 May 20.

Department of Medicine, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.

Background: Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI.

Methods: We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria.

Results: During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73 m/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73 m/year), which was not impacted by source of serum creatinine.

Conclusions: AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria.
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http://dx.doi.org/10.1093/ckj/sfz057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025351PMC
February 2020

Cardiac valvular abnormalities associated with use and cumulative exposure of cabergoline for hyperprolactinemia: the CATCH study.

BMC Endocr Disord 2020 Feb 19;20(1):25. Epub 2020 Feb 19.

Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.

Background: Whether lower dose cabergoline therapy for hyperprolactinemia increases risk of valvular dysfunction remains controversial. We examined valvular abnormalities among asymptomatic adults with hyperprolactinemia treated with dopamine agonists.

Methods: This cross-sectional study was conducted among adults receiving cabergoline or bromocriptine for > 12 months for hyperprolactinemia and had no cardiac-related symptoms. Cardiac valve morphology and function were assessed from transthoracic echocardiograms at the study visit (except for two participants) with evaluation performed blinded to type and duration of dopamine agonist received.

Results: Among 174 participants (mean age 49 ± 13 years, 63% women) without known structural heart disease before starting therapy, 62 received only cabergoline, 63 received only bromocriptine, and 49 received both. Median cabergoline use was 2.8 years in cabergoline only users and 3.2 years for those exposed to both cabergoline and bromocriptine; median bromocriptine use was 5.5 years in bromocriptine only users and 1.1 years for those exposed to both cabergoline and bromocriptine. Compared with bromocriptine only users (17.5%), regurgitation of ≥1 valve was more common for cabergoline only (37.1%, P = 0.02) but not for combined exposure (26.5%, P = 0.26). Compared with bromocriptine only exposure (1.6%), regurgitation of ≥2 valves was more common for cabergoline only (11.3%, P = 0.03) and combined exposure (12.2%, P = 0.04). Cabergoline only users had higher age-sex-adjusted odds for ≥1 valve with grade 2+ regurgitation compared to bromocriptine only users (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI]:1.3-7.5, P = 0.008), but the association for combined exposure to cabergoline and bromocriptine was not significant (aOR 1.7, 95%CI:0.7-4.3, P = 0.26). Compared to bromocriptine only, age-sex-adjusted odds of ≥2 valves with grade 2+ regurgitation were higher for both cabergoline only (aOR 8.4, 95% CI:1.0-72.2, P = 0.05) and combined exposure (aOR 8.8, 95% CI:1.0-75.8, P = 0.05). Cumulative cabergoline exposure > 115 mg was associated with a higher age-sex adjusted odds of ≥2 valves with grade 2+ regurgitation (aOR 9.6, 95%CI:1.1-81.3, P = 0.04) compared to bromocriptine only.

Conclusions: Among community-based adults treated for hyperprolactinemia, cabergoline use and greater cumulative cabergoline exposure were associated with a higher prevalence of primarily mild valvular regurgitation compared with bromocriptine. Research is needed to clarify which patients treated with dopamine agonists may benefit from echocardiographic screening and surveillance.
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http://dx.doi.org/10.1186/s12902-020-0507-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031983PMC
February 2020

Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI.

Clin J Am Soc Nephrol 2020 01 16;15(1):26-34. Epub 2019 Dec 16.

Division of Nephrology, Department of Medicine, and.

Background And Objectives: How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI.

Design, Setting, Participants, & Measurements: This is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders.

Results: Forty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12).

Conclusions: In this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.
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http://dx.doi.org/10.2215/CJN.05800519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946085PMC
January 2020

Impact of AKI on Urinary Protein Excretion: Analysis of Two Prospective Cohorts.

J Am Soc Nephrol 2019 07 24;30(7):1271-1281. Epub 2019 Jun 24.

Department of Medicine, University of California, San Francisco, San Francisco, California.

Background: Prior studies of adverse renal consequences of AKI have almost exclusively focused on eGFR changes. Less is known about potential effects of AKI on proteinuria, although proteinuria is perhaps the strongest risk factor for future loss of renal function.

Methods: We studied enrollees from the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) study and the subset of the Chronic Renal Insufficiency Cohort (CRIC) study enrollees recruited from Kaiser Permanente Northern California. Both prospective cohort studies included annual ascertainment of urine protein-to-creatinine ratio, eGFR, BP, and medication use. For hospitalized participants, we used inpatient serum creatinine measurements obtained as part of clinical care to define an episode of AKI (, peak/nadir inpatient serum creatinine ≥1.5). We performed mixed effects regression to examine change in log-transformed urine protein-to-creatinine ratio after AKI, controlling for time-updated covariates.

Results: At cohort entry, median eGFR was 62.9 ml/min per 1.73 m (interquartile range [IQR], 46.9-84.6) among 2048 eligible participants, and median urine protein-to-creatinine ratio was 0.12 g/g (IQR, 0.07-0.25). After enrollment, 324 participants experienced at least one episode of hospitalized AKI during 9271 person-years of follow-up; 50.3% of first AKI episodes were Kidney Disease Improving Global Outcomes stage 1 in severity, 23.8% were stage 2, and 25.9% were stage 3. In multivariable analysis, an episode of hospitalized AKI was independently associated with a 9% increase in the urine protein-to-creatinine ratio.

Conclusions: Our analysis of data from two prospective cohort studies found that hospitalization for an AKI episode was independently associated with subsequent worsening of proteinuria.
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http://dx.doi.org/10.1681/ASN.2018101036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622423PMC
July 2019

The Association of Polycystic Ovary Syndrome and Gestational Hypertensive Disorders in a Diverse Community-Based Cohort.

J Pregnancy 2019 1;2019:9847057. Epub 2019 Jan 1.

Division of Research, Kaiser Permanente Northern California, USA.

Purpose: To examine the association of polycystic ovary syndrome (PCOS) and pregnancy-induced hypertension (PIH) within a large population of pregnant women in an integrated healthcare system.

Methods: This retrospective study utilized a source cohort of 1023 women with PCOS and 1023 women without PCOS who had a delivered pregnancy within Kaiser Permanente Northern California. Preexisting hypertension was defined by hypertension diagnosis, treatment, or elevated blood pressure prior to 20 weeks of gestation. The development of PIH, including gestational hypertension, preeclampsia/eclampsia, or HELLP (hemolysis, elevated liver enzymes, and low platelet count), was ascertained by chart review. Among women without preexisting hypertension who had a singleton pregnancy, the association of PCOS and PIH was examined using multivariable logistic regression.

Results: Among 1902 women (910 PCOS) with singleton pregnancy, 101 (11.1%) PCOS and 36 (3.6%) non-PCOS women had preexisting hypertension and were excluded. Of the remaining 1765 women, those with PCOS (compared to non-PCOS) were slightly older (mean age 31.2 versus 30.7), more likely to be obese (39.6% versus 15.1%), nulliparous (63.8% versus 43.4%), and conceive with fertility treatment (54.1% versus 1.9%); they also had a higher incidence of PIH (10.8% versus 6.6%), including gestational hypertension (5.8% versus 3.6%) and preeclampsia or HELLP (4.9% versus 3.0%; all p<0.05). PCOS was associated with increased odds of PIH (odds ratio, OR 1.7, 95% confidence interval, CI 1.2-2.4), remaining significant after adjusting for age, race/ethnicity, nulliparity, and fertility treatment; however, findings were attenuated and no longer significant after adjusting for weight status (OR 1.1, CI 0.7-1.7). Maternal PCOS was also associated with preeclampsia/HELLP in unadjusted but not adjusted (OR 1.0, CI 0.5-1.9) analyses. Nulliparity and higher prepregnancy BMI were associated with PIH in both groups.

Conclusion: Compared to women without PCOS, women with PCOS are at higher risk for PIH but this association was not independent of weight status.
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http://dx.doi.org/10.1155/2019/9847057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332934PMC
July 2019

Holo-Lactoferrin Modified Liposome for Relieving Tumor Hypoxia and Enhancing Radiochemotherapy of Cancer.

Small 2019 02 15;15(6):e1803703. Epub 2019 Jan 15.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, 215123, China.

Hypoxic microenvironments in the solid tumor play a negative role in radiotherapy. Holo-lactoferrin (holo-Lf) is a natural protein, which acts as a potential ligand of transferrin receptor (TfR). In this work, an anticancer drug, doxorubicin (Dox)-loaded liposome-holo-Lf nanocomposites, is developed for tumor targeting and imaging guided combined radiochemotherapy. Dox-loaded liposome-holo-Lf (Lf-Liposome-Dox) nanocomposites exhibit significant cellular uptake likely owing to the TfR receptor-mediated targeting accumulation of Lf-Liposome-Dox nanocomposites. Additionally, the nanocomposites exhibit high accumulation in the tumor site after intravenous injection as evidenced from in vivo fluorescence imaging. More importantly, it is found that the holo-Lf has the ability to catalyze the conversion of hydrogen peroxide (H O ) to oxygen for relieving the tumor hypoxic microenvironment. Photoacoustic imaging further confirms the abundant generation of oxygen in the presence of Lf-Liposome-Dox nanocomposites. Based on these findings, in vivo combined radiochemotherapy is performed using Lf-Liposome-Dox as therapeutic agent, achieving excellent cancer treatment effect. The study further promotes the potential biomedical application of holo-Lf in cancer treatment.
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http://dx.doi.org/10.1002/smll.201803703DOI Listing
February 2019

Risk Factors for Recurrent Acute Kidney Injury in a Large Population-Based Cohort.

Am J Kidney Dis 2019 02 25;73(2):163-173. Epub 2018 Oct 25.

Division of Nephrology, Department of Medicine, University of California, San Francisco, CA; Division of Research, Kaiser Permanente Northern California, Oakland, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; Department of Medicine, Stanford University School of Medicine, Stanford, CA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA.

Rationale & Objective: Acute kidney injury (AKI) has numerous sequelae. Repeated episodes of AKI may be an important determinant of adverse outcomes, including chronic kidney disease and death. In a population-based cohort study, we sought to determine the incidence of and predictors for recurrent AKI.

Study Design: Retrospective cohort study.

Setting & Participants: 38,659 hospitalized members of Kaiser Permanente Northern California who experienced an episode of AKI from 2006 to 2013.

Predictors: Demographic, clinical, and laboratory data, including baseline kidney function, proteinuria, hemoglobin level, comorbid conditions, and severity of AKI.

Outcomes: Incidence and predictors of recurrent AKI.

Analytical Approach: Multivariable Cox proportional hazard regression.

Results: 11,048 (28.6%) experienced a second hospitalization complicated by AKI during follow-up (11.2 episodes/100 person-years), with the second episode of AKI occurring a median of 0.6 (interquartile range, 0.2-1.9) years after the first hospitalization. In multivariable analyses, older age, black race, and Hispanic ethnicity were associated with recurrent AKI, along with lower estimated glomerular filtration rate, proteinuria, and anemia. Concomitant conditions, including heart failure, acute coronary syndrome, diabetes, and chronic liver disease, were also multivariable predictors of recurrent AKI. Those who had higher acuity of illness during the initial hospitalization were more likely to have recurrent AKI, but greater AKI severity of the index episode was not independently associated with increased risk for recurrent AKI. In multivariable analysis of matched patients, recurrent AKI was associated with an increased rate of death (HR, 1.66; 95% CI, 1.57-1.77).

Limitations: Analyses were based on clinically available data, rather than protocol-driven timed measurements of kidney function.

Conclusions: Recurrent AKI is a common occurrence after a hospitalization complicated by AKI. Based on routinely available patient characteristics, our findings could facilitate identification of the subgroup of patients with AKI who may benefit from more intensive follow-up to potentially avoid recurrent AKI episodes.
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http://dx.doi.org/10.1053/j.ajkd.2018.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647831PMC
February 2019

Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus.

BMC Nephrol 2018 06 22;19(1):146. Epub 2018 Jun 22.

Division of Nephrology, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA.

Background: Chronic kidney disease (CKD) is highly prevalent but identification of patients at high risk for fast CKD progression before reaching end-stage renal disease in the short-term has been challenging. Whether factors associated with fast progression vary by diabetes status is also not well understood. We examined a large community-based cohort of adults with CKD to identify predictors of fast progression during the first 2 years of follow-up in the presence or absence of diabetes mellitus.

Methods: Within a large integrated healthcare delivery system in northern California, we identified adults with estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m by CKD-EPI equation between 2008 and 2010 who had no previous dialysis or renal transplant, who had outpatient serum creatinine values spaced 10-14 months apart and who did not initiate renal replacement therapy, die or disenroll during the first 2 years of follow-up. Through 2012, we calculated the annual rate of change in eGFR and classified patients as fast progressors if they lost > 4 ml/min/1.73 m per year. We used multivariable logistic regression to identify patient characteristics that were independently associated with fast CKD progression stratified by diabetes status.

Results: We identified 36,195 eligible adults with eGFR 30-59 ml/min/1.73 m and mean age 73 years, 55% women, 11% black, 12% Asian/Pacific Islander and 36% with diabetes mellitus. During 24-month follow-up, fast progression of CKD occurred in 23.0% of patients with diabetes vs. 15.3% of patients without diabetes. Multivariable predictors of fast CKD progression that were similar by diabetes status included proteinuria, age ≥ 80 years, heart failure, anemia and higher systolic blood pressure. Age 70-79 years, prior ischemic stroke, current or former smoking and lower HDL cholesterol level were also predictive in patients without diabetes, while age 18-49 years was additionally predictive in those with diabetes.

Conclusions: In a large, contemporary population of adults with eGFR 30-59 ml/min/1.73 m, accelerated progression of kidney dysfunction within 2 years affected ~ 1 in 4 patients with diabetes and ~ 1 in 7 without diabetes. Regardless of diabetes status, the strongest independent predictors of fast CKD progression included proteinuria, elevated systolic blood pressure, heart failure and anemia.
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http://dx.doi.org/10.1186/s12882-018-0942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014002PMC
June 2018

Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study.

JAMA Cardiol 2018 07;3(7):601-608

Division of Research, Kaiser Permanente Northern California, Oakland.

Importance: Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial.

Objective: To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation.

Design, Setting, And Participants: This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring.

Exposures: The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period.

Main Outcomes And Measures: Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores.

Results: Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (≥11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups.

Conclusions And Relevance: A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.
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http://dx.doi.org/10.1001/jamacardio.2018.1176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145663PMC
July 2018

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

Clin J Am Soc Nephrol 2018 06 17;13(6):833-841. Epub 2018 May 17.

Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; and.

Background And Objectives: AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge.

Design, Setting, Participants, & Measurements: We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records.

Results: Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12).

Conclusions: AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.
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http://dx.doi.org/10.2215/CJN.12591117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989674PMC
June 2018

Risk of Type 2 Diabetes Mellitus following Gestational Diabetes Pregnancy in Women with Polycystic Ovary Syndrome.

J Diabetes Res 2017 20;2017:5250162. Epub 2017 Dec 20.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: This study examines gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) and the risk of type 2 diabetes mellitus (DM) following GDM pregnancy.

Methods: A cohort of 988 pregnant women with PCOS who delivered during 2002-2005 was examined to determine the prevalence and predictors of GDM, with follow-up through 2010 among those with GDM to estimate the risk of DM.

Results: Of the 988 pregnant women with PCOS, 192 (19%) developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the incidence of DM was 2.8 (95% confidence interval (CI) 1.9-4.2) per 100 person-years and substantially higher for those who received pharmacologic treatment for GDM (6.6 versus 1.5 per 100 person-years, < 0.01). The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic treatment for GDM (adjusted hazard ratio 4.1, 95% CI 1.8-9.6). The five-year incidence of DM was 13.1% overall and also higher in the pharmacologic treatment subgroup (27.0% versus 7.1%, < 0.01).

Conclusions: The strongest predictors of GDM among women with PCOS included Asian race and prepregnancy obesity. Pharmacologic treatment of GDM is associated with fourfold higher risk of subsequent DM.
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http://dx.doi.org/10.1155/2017/5250162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750496PMC
August 2018

Acute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient Versus Outpatient Baseline Serum Creatinine.

Kidney Int Rep 2018 Jan 31;3(1):211-215. Epub 2017 Aug 31.

Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

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http://dx.doi.org/10.1016/j.ekir.2017.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762956PMC
January 2018

Esophageal reconstruction: posterior mediastinal or retrosternal route.

J Surg Res 2016 Apr 25;201(2):364-9. Epub 2015 Nov 25.

Department of Cardiothoracic Surgery, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, People's Republic of China.

Background: Although posterior mediastinal (PM) route and retrosternal (RS) route have been used for reconstruction after minimally invasive esophagectomy (MIE), the optimal route remains controversial. This study reviewed our experiences with McKeown MIEs for esophageal cancer and aimed to investigate which route was better for esophageal reconstruction.

Materials And Methods: From December 2011 to December 2013, 103 patients who underwent McKeown MIE and esophageal reconstruction by PM or RS routes were reviewed. The decision regarding which approach was appropriated mainly depended on the first surgeon's preference and experience. Baseline demographics, operative, and postoperative data of the patients were analyzed.

Results: Fifty-six and forty-seven patients receiving PM and RS route reconstruction were reviewed, respectively. Shorter operation time (P = 0.001), less blood loss (P = 0.029), and longer route length (P < 0.001) were observed in PM route compared with RS route. No difference was observed in the resection type, harvested lymph node, intensive care unit and hospital stay, postoperative complications, and in-hospital mortality between the two routes (all P > 0.05).

Conclusions: Both RS route and PM route were safe and effective. PM route was associated with shorter operation time, less blood loss, but longer route length compared with RS route.
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http://dx.doi.org/10.1016/j.jss.2015.11.030DOI Listing
April 2016

Post-discharge Follow-up Characteristics Associated With 30-Day Readmission After Heart Failure Hospitalization.

Med Care 2016 Apr;54(4):365-72

*Division of Research, Kaiser Permanente Northern California, Oakland †Department of Cardiology, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA ‡Duke Clinical Research Institute, Duke University, Durham, NC §Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco, San Francisco ∥Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA.

Background: Readmission within 30 days after hospitalization for heart failure (HF) is a major public health problem.

Objective: To examine whether timing and type of post-discharge follow-up impacts risk of 30-day readmission in adults hospitalized for HF.

Design: Nested matched case-control study (January 1, 2006-June 30, 2013).

Setting: A large, integrated health care delivery system in Northern California.

Participants: Hospitalized adults with a primary diagnosis of HF discharged to home without hospice care.

Measurements: Outpatient visits and telephone calls with cardiology and general medicine providers in non-emergency department and non-urgent care settings were counted as follow-up care. Statistical adjustments were made for differences in patient sociodemographic and clinical characteristics, acute severity of illness, hospitalization characteristics, and post-discharge medication changes and laboratory testing.

Results: Among 11,985 eligible adults, early initial outpatient contact within 7 days after discharge was associated with lower odds of readmission [adjusted odds ratio (OR)=0.81; 95% CI, 0.70-0.94], whereas later outpatient contact between 8 and 30 days after hospital discharge was not significantly associated with readmission (adjusted OR=0.99; 95% CI, 0.82-1.19). Initial contact by telephone was associated with lower adjusted odds of 30-day readmission (adjusted OR=0.85; 95% CI, 0.69-1.06) but was not statistically significant.

Conclusions: In adults discharged to home after hospitalization for HF, outpatient follow-up with a cardiology or general medicine provider within 7 days was associated with a lower chance of 30-day readmission.
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http://dx.doi.org/10.1097/MLR.0000000000000492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800825PMC
April 2016

Cognitive Impairment and Progression of CKD.

Am J Kidney Dis 2016 Jul 10;68(1):77-83. Epub 2016 Mar 10.

Division of Research, Kaiser Permanente Northern California; Oakland, CA.

Background: Cognitive impairment is common among patients with chronic kidney disease (CKD); however, its prognostic significance is unclear. We assessed the independent association between cognitive impairment and CKD progression in adults with mild to moderate CKD.

Study Design: Prospective cohort.

Setting & Participants: Adults with CKD participating in the CRIC (Chronic Renal Insufficiency Cohort) Study. Mean age of the sample was 57.7±11.0 years and mean estimated glomerular filtration rate (eGFR) was 45.0±16.9mL/min/1.73m(2).

Predictor: Cognitive function was assessed with the Modified Mini-Mental State Examination at study entry. A subset of participants 55 years and older underwent 5 additional cognitive tests assessing different domains. Cognitive impairment was defined as a score > 1 SD below the mean score on each test. Covariates included demographics, kidney function, comorbid conditions, and medications.

Outcomes: Incident end-stage renal disease (ESRD) and incident ESRD or 50% decline in baseline eGFR.

Results: In 3,883 CRIC participants, 524 (13.5%) had cognitive impairment at baseline. During a median 6.1 years of follow-up, 813 developed ESRD and 1,062 developed ESRD or a ≥50% reduction in eGFR. There was no significant association between cognitive impairment and risk for ESRD (HR, 1.07; 95% CI, 0.87-1.30) or the composite of ESRD or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.89-1.27). Similarly, there was no association between cognitive impairment and the joint outcome of death, ESRD, or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.91-1.23). Among CRIC participants who underwent additional cognitive testing, we found no consistent association between impairment in specific cognitive domains and risk for CKD progression in adjusted analyses.

Limitations: Unmeasured potential confounders, single measure of cognition for younger participants.

Conclusions: Among adults with CKD, cognitive impairment is not associated with excess risk for CKD progression after accounting for traditional risk factors.
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http://dx.doi.org/10.1053/j.ajkd.2016.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921255PMC
July 2016

Incidence and timing of potentially high-risk arrhythmias detected through long term continuous ambulatory electrocardiographic monitoring.

BMC Cardiovasc Disord 2016 Feb 17;16:35. Epub 2016 Feb 17.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: Ambulatory electrocardiographic (ECG) monitoring is the standard to screen for high-risk arrhythmias. We evaluated the clinical utility of a novel, leadless electrode, single-patient-use ECG monitor that stores up to 14 days of a continuous recording to measure the burden and timing of potentially high-risk arrhythmias.

Methods: We examined data from 122,815 long term continuous ambulatory monitors (iRhythm ZIO® Service, San Francisco) prescribed from 2011 to 2013 and categorized potentially high-risk arrhythmias into two types: (1) ventricular arrhythmias including non-sustained and sustained ventricular tachycardia and (2) bradyarrhythmias including sinus pauses >3 s, atrial fibrillation pauses >5 s, and high-grade heart block (Mobitz Type II or third-degree heart block).

Results: Of 122,815 ZIO® recordings, median wear time was 9.9 (IQR 6.8-13.8) days and median analyzable time was 9.1 (IQR 6.4-13.1) days. There were 22,443 (18.3%) with at least one episode of non-sustained ventricular tachycardia (NSVT), 238 (0.2%) with sustained VT, 1766 (1.4%) with a sinus pause >3 s (SP), 520 (0.4%) with a pause during atrial fibrillation >5 s (AFP), and 1486 (1.2%) with high-grade heart block (HGHB). Median time to first arrhythmia was 74 h (IQR 26-149 h) for NSVT, 22 h (IQR 5-73 h) for sustained VT, 22 h (IQR 7-64 h) for SP, 31 h (IQR 11-82 h) for AFP, and 40 h (SD 10-118 h) for HGHB.

Conclusions: A significant percentage of potentially high-risk arrhythmias are not identified within 48-h of ambulatory ECG monitoring. Longer-term continuous ambulatory ECG monitoring provides incremental detection of these potentially clinically relevant arrhythmic events.
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http://dx.doi.org/10.1186/s12872-016-0210-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756401PMC
February 2016

Anemia and risk for cognitive decline in chronic kidney disease.

BMC Nephrol 2016 Jan 28;17:13. Epub 2016 Jan 28.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.

Background: Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD.

Methods: We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics.

Results: Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6-3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests.

Conclusions: Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline.
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http://dx.doi.org/10.1186/s12882-016-0226-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730636PMC
January 2016

Visit-to-visit variability of blood pressure and death, end-stage renal disease, and cardiovascular events in patients with chronic kidney disease.

J Hypertens 2016 Feb;34(2):244-52

aStanford University School of Medicine, StanfordbDivision of Research, Kaiser Permanente Northern California, OaklandcDepartments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco, California, USA.

Objectives: Visit-to-visit variability of blood pressure (VVV of BP) is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease (CKD) not yet on dialysis.

Methods: We conducted a retrospective study in a community-based cohort of 114 900 adults with CKD stages 3-4 (estimated glomerular filtration rate 15-59 ml/min per 1.73 m). We hypothesized that VVV of BP would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic VVV of BP using three metrics: coefficient of variation, standard deviation of the mean SBP, and average real variability.

Results: The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11-1.34) and hemorrhagic stroke (hazard ratio 1.91; confidence interval 1.36-2.68). VVV of BP was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two metrics of VVV of BP. VVV of BP had inconsistent associations with end-stage renal disease, perhaps because of the relatively low incidences of this outcome.

Conclusion: Higher VVV of BP is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced CKD not yet on dialysis.
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http://dx.doi.org/10.1097/HJH.0000000000000779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818097PMC
February 2016

Elevated BP after AKI.

J Am Soc Nephrol 2016 Mar 1;27(3):914-23. Epub 2015 Jul 1.

Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California;

The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.
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http://dx.doi.org/10.1681/ASN.2014111114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769190PMC
March 2016

Effectiveness and safety of spironolactone for systolic heart failure.

Am J Cardiol 2013 Nov 13;112(9):1427-32. Epub 2013 Sep 13.

Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Cardiology, Kaiser Permanente Santa Clara Medical Center, Santa Clara, California; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California. Electronic address:

Aldosterone receptor antagonists have been shown in randomized trials to reduce morbidity and mortality in adults with symptomatic systolic heart failure. We studied the effectiveness and safety of spironolactone in adults with newly diagnosed systolic heart failure in clinical practice. We identified all adults with newly diagnosed heart failure, left ventricular ejection fraction of <40%, and no previous spironolactone use from 2006 to 2008 in Kaiser Permanente Northern California. We excluded patients with baseline serum creatinine level of >2.5 mg/dl or a serum potassium level of >5.0 mEq/L. We used Cox regression with time-varying covariates to evaluate the independent association between spironolactone use and death, hospitalization, severe hyperkalemia, and acute kidney injury. Among 2,538 eligible patients with a median follow-up of 2.5 years, 521 patients (22%) initiated spironolactone, which was not associated with risk of hospitalization (adjusted hazard ratio 0.91, 95% confidence interval 0.77 to 1.08) or death (adjusted hazard ratio 0.93, confidence interval 0.60 to 1.44). Crude rates of severe hyperkalemia and acute kidney injury during spironolactone use were similar to that seen in clinical trials. Spironolactone was independently associated with a 3.5-fold increased risk of hyperkalemia but not with acute kidney injury. Within a diverse community-based cohort with incident systolic heart failure, use of spironolactone was not independently associated with risks of hospitalization or death. Our findings suggest that the benefits of spironolactone in clinical practice may be reduced compared with other guideline-recommended medications.
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http://dx.doi.org/10.1016/j.amjcard.2013.06.039DOI Listing
November 2013

Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure.

Circ Cardiovasc Qual Outcomes 2013 Sep 10;6(5):525-33. Epub 2013 Sep 10.

Departments of Medicine.

Background: Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF.

Methods And Results: We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent β-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and β-blocker use.

Conclusions: Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.111.000079DOI Listing
September 2013

Effectiveness of β-blockers in heart failure with left ventricular systolic dysfunction and chronic kidney disease.

J Card Fail 2013 Mar;19(3):176-82

Stanford University School of Medicine, Stanford, CA, USA.

Background: Establishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of β-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We examined whether initiation of β-blocker therapy was associated with better outcomes among patients with chronic kidney disease and newly diagnosed heart failure with left ventricular systolic dysfunction.

Methods And Results: We identified 668 adults in the Kaiser Permanente Northern California system from 2006 to 2008 with chronic kidney disease, incident heart failure, left ventricular systolic dysfunction, and no previous β-blocker use. We defined chronic kidney disease as estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) or proteinuria, and we excluded patients receiving dialysis. We used extended Cox regression to assess the association of treatment with death and the combined end point of death or heart failure hospitalization. Initiation of β-blocker therapy was associated with a significantly lower crude risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.35-0.63), but this association was attenuated and no longer significant after multivariable adjustment (HR 0.75, CI 0.51-1.12). β-Blocker therapy was significantly associated with a lower risk of death or heart failure hospitalization even after adjustment for potential confounders (HR 0.67, CI 0.51-0.88).

Conclusions: β-Blocker therapy is associated with lower risk of death or heart failure hospitalization among patients with chronic kidney disease, incident heart failure, and left ventricular systolic dysfunction.
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http://dx.doi.org/10.1016/j.cardfail.2013.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126798PMC
March 2013

Prevalence of cervical insufficiency in polycystic ovarian syndrome.

Hum Reprod 2012 Sep 14;27(9):2837-42. Epub 2012 Jun 14.

Department of Obstetrics and Gynecology, The Permanente Medical Group, San Francisco, CA 94115, USA.

Background: Pregnant women with polycystic ovarian syndrome (PCOS) experience a greater rate of adverse obstetrical outcomes compared with non-PCOS women. We examined the prevalence and incidence of cervical insufficiency (CI) in a community cohort of pregnant women with and without PCOS.

Methods: A retrospective cohort study was conducted within a large integrated health care delivery system among non-diabetic PCOS women with second or third trimester delivery during 2002-2005 (singleton or twin gestation). PCOS was defined by Rotterdam criteria. A non-PCOS comparison group matched for delivery year and hospital facility was used to estimate the background rate of CI. Women were designated as having new CI diagnosed in the index pregnancy (based on cervical dilation and/or cervical shortening) and prior CI based on prior diagnosis of CI with prophylactic cerclage placed in the subsequent pregnancy.

Results: We identified 999 PCOS women, of whom 29 (2.9%) had CI. There were 18 patients with new CI and 11 with prior CI having prophylactic cerclage placement; four CI patients had twin gestation. In contrast, only five (0.5%) non-PCOS women had CI: two with new CI and three with prior CI. The proportion of newly diagnosed incident CI (1.8 versus 0.2%) or prevalent CI (2.9 versus 0.5%) was significantly greater for PCOS compared with non-PCOS pregnant women (both P < 0.01). Among PCOS women, CI prevalence was particularly high among South Asians (7.8%) and Blacks (17.5%) compared with Whites (1%) and significantly associated with gonadotropin use (including in vitro fertilization). Overall, the PCOS status was associated with an increased odds of prevalent CI pregnancy (adjusted odds ratio 4.8, 95% confidence interval 1.5-15.4), even after adjusting for maternal age, nulliparity, race/ethnicity, body mass index and fertility treatment.

Conclusion: In this large and ethnically diverse PCOS cohort, we found that CI occurred with a higher than expected frequency in PCOS women, particularly among South Asian and Black women. PCOS women with CI were also more likely to have received gonadotropin therapy. Future studies should examine whether natural and hormone-altered PCOS is a risk factor for CI, the role of race/ethnicity, fertility drugs and consideration for heightened mid-trimester surveillance in higher risk subgroups of pregnant women with PCOS.
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http://dx.doi.org/10.1093/humrep/des193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415288PMC
September 2012

Oral health considerations in older women receiving oral bisphosphonate therapy.

J Am Geriatr Soc 2011 May 3;59(5):916-22. Epub 2011 May 3.

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.

Recent reports of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have increased awareness of oral health in patients receiving osteoporosis therapy. This study describes the demographic, oral health, and clinical characteristics of a contemporary population of women aged 50 and older undergoing oral bisphosphonate treatment who returned a mailed questionnaire pertaining to dental symptoms. The study, as previously reported, was conducted within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. The cohort included 7,909 women with bisphosphonate exposure of at least 1 year, with a subset of 923 women reporting dental symptoms who underwent clinical examination. Overall, the average age was 71 ± 9; 70% were white, and 74% had at least some college education. Nearly two-thirds had received oral bisphosphonate therapy for 3 or more years. Most reported daily tooth brushing, 85% had had a dental examination in the past year, 22% reported denture use, and 6% reported moderate to severe periodontal disease. Oral healthcare patterns varied according to age and race and ethnicity. Five hundred seven (6.4%) women reported a tooth extraction in the prior year, of whom two developed BRONJ (0.4%). Tori or exostoses were found in 28% of examined participants with dental symptoms; these were predominantly in the lingual mandible and palate, with palatal BRONJ occurring in 1.6% of symptomatic participants with palatal tori. In summary, among older women with bisphosphonate exposure, oral health varied according to patient characteristics, and BRONJ occurred more frequently after tooth extraction or on palatal tori. These data support efforts to optimize oral health and to identify risk factors for BRONJ in older individuals receiving bisphosphonate drugs.
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http://dx.doi.org/10.1111/j.1532-5415.2011.03371.xDOI Listing
May 2011

Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure.

J Oral Maxillofac Surg 2010 Feb 24;68(2):243-53. Epub 2009 Sep 24.

Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Purpose: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy.

Materials And Methods: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy.

Results: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ.

Conclusions: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.
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http://dx.doi.org/10.1016/j.joms.2009.03.050DOI Listing
February 2010

Comparative effectiveness of different beta-adrenergic antagonists on mortality among adults with heart failure in clinical practice.

Arch Intern Med 2008 Dec;168(22):2415-21

Division of Research, Kaiser Permanente of Northern California, Oakland, CA 94612-2304, USA.

Background: Randomized trials have demonstrated the efficacy of selected beta-blockers in systolic heart failure, but the comparative effectiveness of different beta-blockers in practice is poorly understood.

Methods: We compared mortality associated with different beta-blockers following hospitalization for heart failure between 2001 and 2003. Longitudinal exposure to beta-blockers was ascertained from pharmacy databases. Patient characteristics and other medication use were identified from administrative, hospitalization, outpatient, and pharmacy databases. Death was identified from administrative, state mortality, and Social Security Administration databases. Multivariate Cox regression was used to examine the association between different beta-blockers and death.

Results: Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44).

Conclusions: Compared with atenolol, the adjusted risks of death were slightly higher with shorter-acting metoprolol tartrate but did not significantly differ for carvedilol in adults with heart failure. Our results should be interpreted cautiously and they suggest the need for randomized trials within real-world settings comparing a broader spectrum of beta-blockers for heart failure.
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http://dx.doi.org/10.1001/archinternmed.2008.506DOI Listing
December 2008

Comparative effectiveness of beta-adrenergic antagonists (atenolol, metoprolol tartrate, carvedilol) on the risk of rehospitalization in adults with heart failure.

Am J Cardiol 2007 Aug 26;100(4):690-6. Epub 2007 Jun 26.

Division of Research, Kaiser Permanente of Northern California, Oakland, California, USA.

Placebo-controlled randomized trials have demonstrated the efficacy of selected beta blockers on outcomes in chronic heart failure (HF), but the relative effectiveness of different beta blockers in usual clinical care is poorly understood. We compared 12-month risk of rehospitalization for HF associated with receipt of different beta blockers in 7,883 adults hospitalized for HF within 2 large health plans between January 1, 2001 and December 31, 2002. Beta-blocker use was ascertained from electronic pharmacy databases and readmissions within 12 months were identified from hospital discharge databases. Extended Cox regression was used to examine the association between receipt of different beta blockers and risk of readmission for HF after adjustment for potential confounders. During follow-up, there were 3,234 person-years of exposure to beta blockers (39.3% atenolol, 42.0% metoprolol tartrate, 12.3% carvedilol, and 6.4% other). Crude 12-month rates of readmissions for HF were high overall (42.6 per 100 person-years). After adjustment for potential confounders, cumulative exposure to each beta blocker, and propensity to receive carvedilol compared with atenolol, adjusted risks of readmission were not significantly different for metoprolol tartrate (adjusted hazard ratio 0.95, 95% confidence interval 0.85 to 1.05) or for carvedilol (adjusted hazard ratio 0.92, 95% confidence interval 0.74 to 1.14). In conclusion, in a contemporary cohort of high-risk patients hospitalized with HF, we found that adjusted risks of rehospitalization for HF within 12 months were not significantly different in patients receiving atenolol, shorter-acting metoprolol tartrate, or carvedilol.
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http://dx.doi.org/10.1016/j.amjcard.2007.03.084DOI Listing
August 2007

Statin therapy and risks for death and hospitalization in chronic heart failure.

JAMA 2006 Nov;296(17):2105-11

Division of Research, Kaiser Permanente of Northern California, Oakland 94612, USA.

Context: Whether statin therapy has beneficial effects on clinical outcomes in patients with heart failure is unclear.

Objective: To evaluate the association between initiation of statin therapy and risks for death and hospitalization among adults with chronic heart failure.

Design, Setting, And Patients: Propensity-adjusted cohort study of adults diagnosed with heart failure who were eligible for lipid-lowering therapy but had no previous known statin use, within an integrated health care delivery system in northern California between January 1, 1996, and December 31, 2004. Statin use was estimated from filled outpatient prescriptions in pharmacy databases.

Main Outcome Measures: All-cause death and hospitalization for heart failure during a median of 2.4 years of follow-up. We examined the independent relationships between statin therapy and risks for adverse events overall and stratified by the presence or absence of coronary heart disease after multivariable adjustment for potential confounders.

Results: Among 24,598 adults diagnosed with heart failure who had no prior statin use, those initiating statin therapy (n = 12,648; 51.4%) were more likely to be younger, male, and have known cardiovascular disease, diabetes, and hypertension. There were 8235 patients who died. Using an intent-to-treat approach, incident statin use was associated with lower risks of death (age- and sex-adjusted rate of 14.5 per 100 person-years with statin therapy vs 25.3 per 100 person-years without statin therapy; adjusted hazard ratio, 0.76 [95% confidence interval, 0.72-0.80]) and hospitalization for heart failure (age- and sex-adjusted rate of 21.9 per 100 person-years with statin therapy vs 31.1 per 100 person-years without statin therapy; adjusted hazard ratio, 0.79 [95% confidence interval, 0.74-0.85]) even after adjustment for the propensity to take statins, cholesterol level, use of other cardiovascular medications, and other potential confounders. Incident statin use was associated with lower adjusted risks of adverse outcomes in patients with or without known coronary heart disease.

Conclusion: Among adults diagnosed with heart failure who had no prior statin use, incident statin use was independently associated with lower risks of death and hospitalization among patients with or without coronary heart disease.
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http://dx.doi.org/10.1001/jama.296.17.2105DOI Listing
November 2006
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