Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Billing codes are frequently used to identify AKI events in epidemiologic research. The goals of this study were to validate billing code-identified AKI against the current AKI consensus definition and to ascertain whether sensitivity and specificity vary by patient characteristic or over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:The study population included 10,056 Atherosclerosis Risk in Communities study participants hospitalized between 1996 and 2008. Billing code-identified AKI was compared with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based criteria (AKIcr) and an approximation of the 2012 KDIGO creatinine- and urine output-based criteria (AKIcr_uop) in a subset with available outpatient data. Sensitivity and specificity of billing code-identified AKI were evaluated over time and according to patient age, race, sex, diabetes status, and CKD status in 546 charts selected for review, with estimates adjusted for sampling technique. RESULTS:A total of 34,179 hospitalizations were identified; 1353 had a billing code for AKI. The sensitivity of billing code-identified AKI was 17.2% (95% confidence interval [95% CI], 13.2% to 21.2%) compared with AKIcr (n=1970 hospitalizations) and 11.7% (95% CI, 8.8% to 14.5%) compared with AKIcr_uop (n=1839 hospitalizations). Specificity was >98% in both cases. Sensitivity was significantly higher in the more recent time period (2002-2008) and among participants aged 65 years and older. Billing code-identified AKI captured a more severe spectrum of disease than did AKIcr and AKIcr_uop, with a larger proportion of patients with stage 3 AKI (34.9%, 19.7%, and 11.5%, respectively) and higher in-hospital mortality (41.2%, 18.7%, and 12.8%, respectively). CONCLUSIONS:The use of billing codes to identify AKI has low sensitivity compared with the current KDIGO consensus definition, especially when the urine output criterion is included, and results in the identification of a more severe phenotype. Epidemiologic studies using billing codes may benefit from a high specificity, but the variation in sensitivity may result in bias, particularly when trends over time are the outcome of interest.

BACKGROUND:Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. STUDY DESIGN/METHODS:Nationally representative cross-sectional study. SETTING & PARTICIPANTS/METHODS:4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. PREDICTORS/METHODS:Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. OUTCOMES & MEASUREMENTS/METHODS:Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. RESULTS:Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. LIMITATIONS/CONCLUSIONS:CKD and LDL cholesterol defined using a single laboratory value. CONCLUSIONS:Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy.

BACKGROUND:HbA1c is the standard measure by which to monitor long-term (2-3 months) glucose control in people with diabetes and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are markers of short-term (2-4 weeks) glycaemic control that might add complementary prognostic information to HbA1c. Our aim was to clarify the performance of fructosamine and glycated albumin measurements for identifying people at risk of incident diabetes or diabetic complications. METHODS:We measured glycated albumin and fructosamine in blood samples from 11 348 adults without diabetes and 958 adults diagnosed with diabetes mellitus (both type 1 and 2) who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) study in 1990-92 (baseline). We assessed the associations of fructosamine and glycated albumin with risk of incident diabetes, retinopathy, and risk of incident chronic kidney disease (CKD), during two decades of follow-up. We compared these associations with those of HbA1c with incident diabetes, retinopathy, and CKD. For analyses of associations with incident diabetes and CKD, adjusted hazard ratios (HRs) and their corresponding 95% CIs were estimated using Cox proportional hazards models. Model discrimination was assessed using Harrell's C statistic. FINDINGS/RESULTS:The HRs for incident diabetes were 4·96 (4·36-5·64) for fructosamine above the 95th percentile and 6·17 (5·45-6·99) for glycated albumin above the 95th percentile. Associations were attenuated but persisted after adjustment for HbA1c. Fructosamine and glycated albumin were strongly associated with retinopathy (p<0·0001 for trend). The multivariable-adjusted HRs for CKD for people with fructosamine and glycated albumin above the 95th percentile were 1·50 (95% CI 1·22-1·85) and 1·48 (1·20-1·83), respectively, when compared with people with no diabetes and fructosamine or glycated albumin below the 75th percentile. Prediction of incident CKD by fructosamine (C statistic 0·717) and glycated albumin (0·717) were nearly as strong as by HbA1c (0·726), but HbA1c outperformed fructosamine and glycated albumin for prediction of incident diabetes with C statistics of 0·760, 0·706, and 0·703, respectively. INTERPRETATION/CONCLUSIONS:Fructosamine and glycated albumin were strongly associated with incident diabetes and its microvascular complications, with prognostic value comparable to HbA1c. FUNDING/BACKGROUND:National Heart, Lung, and Blood Institute.

OBJECTIVE Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetes complications. RESEARCH DESIGN AND METHODS We analyzed data from adult participants from the 1999-2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ≥60 mL/min/1.73 m(2)) or reduced (eGFR <60 mL/min/1.73 m(2)) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations. RESULTS Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (odds ratio 3.1 [95% CI 1.9-4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality. CONCLUSIONS More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetes complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study.

Pain modulation by placebo mechanisms is one of the most robust and best-studied phenomena, yet almost all research investigating the mechanisms and implications of the placebo analgesia are based on adult research. After highlighting crucial aspects that need to be considered in studying pain modulation in children, this comprehensive review examines studies related to pain modulation with an emphasis on factors such as age, neural development and pain measures. We critically discuss psychological mechanisms underlying placebo effects, including (1) verbally induced expectations, (2) conditioning and learning mechanisms, and (3) child-parent-physician interactions. Taken together, research suggests that placebo mechanisms can affect therapeutic outcomes and potentially be exploited clinically to improve clinical outcomes in pediatric population. Recommendations for further investigating the mechanistic bases and harnessing placebo effects for supportive therapeutic applications are given.

Glial cell line-derived neurotrophic factor (GDNF) exerts neurotrophic and neuroprotective effects on substantia nigra (SN) dopamine neurons and has great therapeutic potential for Parkinson's disease (PD). Hindering this potential is the fact that GDNF cannot cross the blood-brain barrier. The aim of this study was to assess the effects of GDNF administered by the intranasal route in normal rats, and in the unilateral 6-hydroxydopamine (6-OHDA) model of PD. In the first study, rats received single intranasal doses of 50-μg GDNF in phosphate-buffered saline (PBS) or cationic liposomes, but no 6-OHDA. In the second study, rats were nasally administered 10, 50 or 150 μg of GDNF in PBS or cationic liposomes 1h before injection of 6-OHDA. All groups were sacrificed 3-4 weeks later. Both intranasal GDNF treatments induced a neurotrophic effect in the SN insofar as the number of tyrosine hydroxylase (TH)-positive neurons was significantly higher than in controls given intranasal PBS liposomes. Dopamine cell counts were also higher in the intact SN of 6-OHDA-lesioned rats compared to controls given PBS liposomes. Most importantly, intranasal GDNF provided significant neuroprotective efficacy indicated by greater TH immunostaining density in the lesioned versus intact SN of rats given single 50-μg doses of GDNF in PBS, or 150-μg doses of liposomal GDNF, compared to lesioned rats given PBS liposomes. Three 50-μg doses given at daily intervals (1 day before, 1h before, and 1 day after 6-OHDA) provided even greater protection than single 150-μg doses. Multiple doses at short intervals may therefore provide greater neuroprotection than single bolus doses. These results demonstrate both a neurotrophic effect of intranasal GDNF in the intact SN as well as neuroprotective efficacy in the unilateral 6-OHDA model, supporting pursuit of this approach as a potential treatment for PD.

OBJECTIVE:Pediatric loss of control (LOC) eating is predictive of partial- and full-syndrome binge eating disorder. The interpersonal model proposes that LOC eating is used to cope with negative mood states resulting from interpersonal distress, possibly on a momentary level. We therefore examined temporal associations between interpersonal problems, negative affect, and LOC eating among overweight adolescent girls using ecological momentary assessment (EMA). METHOD/METHODS:Thirty overweight and obese (≥85th body mass index (BMI) percentile; BMI: M = 36.13, SD = 7.49 kg/m(2)) adolescent females (Age: M = 14.92, SD = 1.54 y; 60.0% African American) who reported at least two LOC episodes in the past month completed self-report momentary ratings of interpersonal problems, state affect, and LOC eating for 2 weeks. A series of 2-level multilevel models with centering within subjects was conducted. RESULTS:Between- and within-subjects interpersonal problems (p's < .05), but not between- (p = .12) or within- (p = .32) subjects negative affect predicted momentary LOC eating. At the between-subjects level, interpersonal problems significantly predicted increases in negative affect (p < 001). DISCUSSION/CONCLUSIONS:Naturalistic data lend support to the predictive value of interpersonal problems for LOC eating among adolescents. Interventions targeting interpersonal factors on a momentary basis may be useful during this developmental stage.

OBJECTIVES/OBJECTIVE:Venous invasion is common in advanced renal cell carcinoma (RCC) due to the unique biology of this cancer. The presence of a tumor thrombus often makes clinical management challenging. In this review, we detail specific preoperative, perioperative, and surgical strategies involving the care of the complex kidney cancer patient with venous tumor involvement. METHODS:We performed a comprehensive review of selected peer-reviewed publications regarding RCC tumor thrombus biology, medical and surgical management techniques, and immediate and long-term outcomes. RESULTS:The perioperative management may require special imaging techniques, preoperative testing, very recent imaging, and consultation with other surgical services. There are various approaches to these patients as the clinical presentation, stage of disease, primary tumor size, level of thrombus, degree of venous occlusion, presence of bland thrombus, and primary tumor laterality influence management. Select patients with metastatic disease can do well with cytoreductive nephrectomy and thrombectomy. Those with localized disease have a high risk of recurrence; however, some patients can exhibit durable survival with surgery alone. The evolving surgical and medical treatments are discussed. CONCLUSIONS:Even when these surgeries are performed in high volume centers, significant perioperative complications are common and greater complications are seen with higher thrombus extent. If surgery is attempted, it is important for urologic oncologists to follow strict attention to specific surgical principles. These general principles include complete vascular control, avoidance of thrombus embolization, close hemodynamic monitoring, and institutional resources for caval resection/replacement and venous bypass if necessary.

OBJECTIVES/OBJECTIVE:Housing First is a supportive housing model for persons with histories of chronic homelessness that emphasizes client-centered services, provides immediate housing, and does not require treatment for mental illness or substance abuse as a condition of participation. Previous studies of Housing First have found reduced governmental costs and improved personal well-being among participants. However, variations in real-world program implementation require better understanding of the relationship between implementation and outcomes. This study investigated the effects of Housing First implementation on housing and substance use outcomes. METHODS:Study participants were 358 individuals with histories of chronic homelessness and problematic substance use. Clients were housed in nine scatter-site Housing First programs in New York City. Program fidelity was judged across a set of core Housing First components. Client interviews at baseline and 12 months were used to assess substance use. RESULTS:Clients in programs with greater fidelity to consumer participation components of Housing First were more likely to be retained in housing and were less likely to report using stimulants or opiates at follow-up. CONCLUSIONS:Consistently implemented Housing First principles related to consumer participation were associated with superior housing and substance use outcomes among chronically homeless individuals with a history of substance use problems. The study findings suggest that program implementation is central to understanding the potential of Housing First to help clients achieve positive housing and substance use outcomes.