Comorbidities and complications in adults with pyruvate kinase deficiency.

OBJECTIVES: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified. METHODS: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age- and sex-matched cohort from a general insured US population without PK deficiency. RESULTS: Compared with the matched population (n = 1220), patients with PK deficiency (n = 122) had significantly higher lifetime rates of osteoporosis, liver cirrhosis, and pulmonary hypertension; splenectomy and cholecystectomy rates were also significantly higher in the 8 years before the index date. Sixty-five (53.3%) patients with PK deficiency were classified as regularly transfused, 30 (24.6%) as occasionally transfused, and 27 (22.1%) as never transfused. Regularly transfused patients were significantly more likely than never transfused patients to have had splenectomy, cholecystectomy, and/or thrombosis. Liver iron overload was reported in 62% of patients and occurred regardless of transfusion cohort. CONCLUSIONS: Even never transfused patients with PK deficiency had higher rates of select comorbidities and complications than individuals without PK deficiency.

Effect of food insecurity on chronic kidney disease in lower-income Americans.

BACKGROUND: The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population. METHODS: We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression. RESULTS: In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. CONCLUSION: Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.

Americans' use of dietary supplements that are potentially harmful in CKD.

BACKGROUND: The prevalence in the United States of dietary supplement use that may be harmful to those with chronic kidney disease (CKD) is unknown. We sought to characterize potentially harmful supplement use by individual CKD status. STUDY DESIGN: Cross-sectional national survey (National Health and Nutrition Examination Survey, 1999-2008). SETTING & PARTICIPANTS: Community-based survey of 21,169 nonpregnant noninstitutionalized US civilian adults (aged ≥20 years). PREDICTOR: CKD status (no CKD, at risk of CKD [presence of diabetes, hypertension, and/or cardiovascular disease], stages 1/2 [albuminuria only (albumin-creatinine ratio ≥30 mg/g)], or stages 3/4 [estimated glomerular filtration rate of 15-59 mL/min/1.73 m(2)]). OUTCOME: Self-reported use of dietary supplements containing any of 37 herbs the National Kidney Foundation identified as potentially harmful in the setting of CKD. MEASUREMENTS: Albuminuria and estimated glomerular filtration rate assessed from urine and blood samples; demographics and comorbid conditions assessed by standardized questionnaire. RESULTS: An estimated 8.0% of US adults reported potentially harmful supplement use within the last 30 days. A lower crude estimated prevalence of potentially harmful supplement use was associated with higher CKD severity (no CKD, 8.5%; at risk, 8.0%; stages 1/2, 6.1%; and stages 3/4, 6.2%; P < 0.001). However, after adjustment for confounders, those with or at risk of CKD were as likely to use a potentially harmful supplement as those without CKD: at-risk OR, 0.93 (95% CI, 0.79-1.09); stages 1/2 OR, 0.83 (95% CI, 0.64-1.08); and stages 3/4 OR, 0.87 (95% CI, 0.63-1.18); all versus no CKD. LIMITATIONS: Herb content was not available and the list of potentially harmful supplements examined is unlikely to be exhaustive. CONCLUSIONS: The use of dietary supplements potentially harmful to people with CKD is common regardless of CKD status. Health care providers should discuss the use and potential risks of supplements with patients with and at risk of CKD.

Estimating prevalence of CKD stages 3-5 using health system data.

BACKGROUND: The feasibility of using health system data to estimate prevalence of chronic kidney disease (CKD) stages 3-5 was explored. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: A 5% national random sample of patients from the Veterans Affairs (VA) health care system, enrollees in a managed care plan in Michigan (M-CARE), and participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). PREDICTOR: Observed CKD prevalence estimates in the health system population were calculated as patients with an available outpatient serum creatinine measurement with estimated glomerular filtration rate <60 mL/min/1.73 m(2), among those with at least one outpatient visit during the year. OUTCOMES & MEASUREMENTS: A logistic regression model was fitted using data from the 2005-2006 NHANES to predict CKD prevalence in those untested for serum creatinine in the health system population, adjusted for demographics and comorbid conditions. Model results then were combined with the observed prevalence in tested patients to derive an overall predicted prevalence of CKD within the health systems. RESULTS: Patients in the VA system were older, had more comorbid conditions, and were more likely to be tested for serum creatinine than those in the M-CARE system. Observed prevalences of CKD stages 3-5 were 15.6% and 0.9% in the VA and M-CARE systems, respectively. Using data from NHANES, the overall predicted prevalences of CKD were 20.4% and 1.6% in the VA and M-CARE systems, respectively. LIMITATIONS: Health system data quality was limited by missing data for laboratory results and race. A single estimated glomerular filtration rate value was used to define CKD, rather than persistence over 3 months. CONCLUSIONS: Estimation of CKD prevalence within health care systems is feasible, but discrepancies between observed and predicted prevalences suggest that this approach is dependent on data availability and quality of information for comorbid conditions, as well as the frequency of testing for CKD in the health care system.

Validation of CKD and related conditions in existing data sets: A systematic review.

BACKGROUND: Accurate classification of individuals with kidney disease is vital to research and public health efforts aimed at improving health outcomes. Our objective is to identify and synthesize published literature evaluating the accuracy of existing data sources related to kidney disease. STUDY DESIGN: A systematic review of studies seeking to validate the accuracy of the underlying data relevant to kidney disease. SETTING & POPULATION: US-based and international studies covering a wide range of both outpatient and inpatient study populations. SELECTION CRITERIA FOR STUDIES: Any English-language study investigating the prevalence or cause of kidney disease, existence of comorbid conditions, or cause of death in patients with chronic kidney disease (CKD). All definitions and stages of CKD, including end-stage renal disease (ESRD), were accepted. INDEX TESTS: Presence of a kidney disease-related variable in existing data sets, including administrative data sets and disease registries. REFERENCE TESTS: Presence of a kidney disease-related variable defined using laboratory criteria or medical record review. RESULTS: 30 studies were identified. Most studies investigated the accuracy of kidney disease reporting, comparing coded renal disease with that defined using estimated glomerular filtration rate. The sensitivity of coded renal disease varied widely (0.08-0.83). Specificity was higher, with all studies reporting values ≥0.90. Studies evaluating the cause of CKD, comorbid conditions, and cause of death in patients with CKD used ESRD or transplant populations exclusively, and accuracy was highly variable compared with ESRD registry data. LIMITATIONS: Only English-language studies were evaluated. CONCLUSIONS: Given the heterogeneous results of validation studies, a variety of attributes of existing data sources, including the accuracy of individual data items within these sources, should be considered carefully before use in research, quality improvement, and public health efforts.

Nonsteroidal anti-inflammatory drug use among persons with chronic kidney disease in the United States.

PURPOSE: Because avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended for most individuals with chronic kidney disease (CKD), we sought to characterize patterns of NSAID use among persons with CKD in the United States. METHODS: A total of 12,065 adult (aged 20 years or older) participants in the cross-sectional National Health and Nutrition Examination Survey (1999-2004) responded to a questionnaire regarding their use of over-the-counter and prescription NSAIDs. NSAIDs (excluding aspirin and acetaminophen) were defined by self-report. CKD was categorized as no CKD, mild CKD (stages 1 and 2; urinary albumin-creatinine ratio of ≥ 30 mg/g) and moderate to severe CKD (stages 3 and 4; estimated glomerular filtration rate of 15-59 mL/min/1.73 m(2)). Adjusted prevalence was calculated using multivariable logistic regression with appropriate population-based weighting. RESULTS: Current use (nearly every day for 30 days or longer) of any NSAID was reported by 2.5%, 2.5%, and 5.0% of the US population with no, mild, and moderate to severe CKD, respectively; nearly all of the NSAIDs used were available over-the-counter. Among those with moderate to severe CKD who were currently using NSAIDs, 10.2% had a current NSAID prescription and 66.1% had used NSAIDs for 1 year or longer. Among those with CKD, disease awareness was not associated with reduced current NSAID use: (3.8% vs 3.9%, aware vs unaware; P=.979). CONCLUSIONS: Physicians and other health care clinicians should be aware of use of NSAIDs among those with CKD in the United States and evaluate NSAID use in their CKD patients.

Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study.

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001-2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ([Formula: see text] 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan-Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors-51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8-17.9) and 13.4 (95% CI = 9.5-16.3) in PD-L1+ and PD-L1- tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74-1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63-1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39-0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.

Programmed cell death ligand-1 expression and survival in a cohort of patients with non-small cell lung cancer receiving first-line through third-line therapy in Denmark.

BACKGROUND: PD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status. METHODS: Danish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs. RESULTS: PD-L1 TC and IC ≥ 25 % were observed in 24.3 %-31.0 % and 11.7-14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %-8.8 % and 26.5 %-30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI: 0.75-1.22), second- (1.08, 0.81-1.42), or third-line (0.94, 0.74-1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI: 0.36-0.86) and third-line (0.69, 0.49-0.97) but not first-line (1.00, 0.70-1.41) therapy. CONCLUSION: No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.

Estimating population distributions when some data are below a limit of detection by using a reverse Kaplan-Meier estimator.

BACKGROUND: Data with some values below a limit of detection (LOD) can be analyzed using methods of survival analysis for left-censored data. The reverse Kaplan-Meier (KM) estimator provides an effective method for estimating the distribution function and thus population percentiles for such data. Although developed in the 1970s and strongly advocated since then, it remains rarely used, partly due to limited software availability. METHODS: In this paper, the reverse KM estimator is described and is illustrated using serum dioxin data from the University of Michigan Dioxin Exposure Study (UMDES) and the National Health and Nutrition Examination Survey (NHANES). Percentile estimates for left-censored data using the reverse KM estimator are compared with replacing values below the LOD with the LOD/2 or LOD/ radical2. RESULTS: When some LODs are in the upper range of the complete values, and/or the percent censored is high, the different methods can yield quite different percentile estimates. The reverse KM estimator, which is the nonparametric maximum likelihood estimator, is the preferred method. Software options are discussed: The reverse KM can be calculated using software for the KM estimator. The JMP and SAS (SAS Institute, Cary, NC) and Minitab (Minitab, Inc, State College, PA), software packages calculate the reverse KM directly using their Turnbull estimator routines. CONCLUSION: The reverse KM estimator is recommended for estimation of the distribution function and population percentiles in preference to commonly used methods such as substituting LOD/2 or LOD/ radical2 for values below the LOD, assuming a known parametric distribution, or using imputation to replace the left-censored values.

Estimation of background serum 2,3,7,8-TCDD concentrations by using quantile regression in the UMDES and NHANES populations.

BACKGROUND: The goal of the present study was to quantify the population-based background serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using data from the reference population of the 2005 University of Michigan Dioxin Exposure Study (UMDES) and the 2003-2004 National Health and Nutrition Examination Survey (NHANES). METHODS: Multiple imputation was used to impute the serum TCDD concentrations below the limit of detection by combining the 2 data sources. The background mean, quartiles, and 95th percentile serum TCDD concentrations were estimated by age and sex by using linear and quantile regressions for complex survey data. RESULTS: Any age- and sex-specific mean, quartiles, and 95th percentiles of background serum TCDD concentrations of study participants between ages 18 and 85 years can be estimated from the regressions for the UMDES reference population and the NHANES non-Hispanic white population. For example, for a 50-year-old man in the reference population of UMDES, the mean, quartiles, and 95th percentile serum TCDD concentrations are estimated to be 1.1, 0.6, 1.1, 1.8, and 3.3 parts per trillion, respectively. The study also shows that the UMDES reference population is a valid reference population for serum TCDD concentrations for other predominantly white populations in Michigan. CONCLUSION: The serum TCDD concentrations increased with age and increased more over age in women than in men, and hence estimation of background concentrations must be adjusted for age and sex. The methods and results discussed in this article have wide application in studies of the concentrations of chemicals in human serum and in environmental samples.

Case report: human exposure to dioxins from clay.

CONTEXT: For the general population, the dominant source of exposure to dioxin-like compounds is food. As part of the University of Michigan Dioxin Exposure Study (UMDES), we measured selected polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in serum of 946 subjects who were a representative sample of the general population in five Michigan counties. CASE PRESENTATION: The total toxic equivalency (TEQ; based on 2005 World Health Organization toxic equivalency factors) of serum from the index case was 211 ppt on a lipid-adjusted basis, which was the highest value observed in the UMDES study population. This subject had no apparent opportunity for exposure to dioxins, except that she had lived on property with soil contaminated with dioxins for almost 30 years, and had been a ceramics hobbyist for > 30 years. Soil from her property and clay that she used for ceramics were both contaminated with dioxins, but the congener patterns differed. DISCUSSION: The congener patterns in this subject's serum, soil, and ceramic clay suggest strongly that the dioxin contamination in clay and not soil was the dominant source of dioxin contamination in her serum. RELEVANCE TO PUBLIC HEALTH PRACTICE: It appears that ceramic clay, in particular the process of firing clay with unvented kilns, can be a significant nonfood and nonindustrial source of human exposure to dioxins among ceramics hobbyists. The extent of human exposure from ceramic clay is unclear, but it may be widespread. Further work is needed to more precisely characterize the routes of exposure.

Perceived stress across the midlife: longitudinal changes among a diverse sample of women, the Study of Women's health Across the Nation (SWAN).

Background: In women, midlife is a period of social and physiological change. Ostensibly stressful, cross-sectional studies suggest women experience decreasing stress perceptions and increasing positive outlook during this life stage. The aim of this paper was to describe the longitudinal changes in perceived stress as women transitioned through the midlife. Methods: Premenopausal women (n = 3044) ages 42-52 years at baseline, were recruited from seven sites in the Study of Women's Health Across the Nation, and followed approximately annually over 13 visits with assessment of perceived stress and change in menopausal status. Longitudinal regression models were used to assess the effects of age, menopausal status and baseline sociodemographic variables on the trajectory of perceived stress over time. Results: At baseline, mean age was 46.4 ± 2.7 years; participants were white (47%), black (29%), Hispanic (7%), Japanese (9%), or Chinese (8%). Hispanic women, women with lesser educational attainment, and women reporting financial hardship were each more likely to report high perceived stress levels at baseline (all p < 0.0001). After adjustment for baseline sociodemographic factors, perceived stress decreased over time for most women (p < 0.0001), but increased for both Hispanic and white participants at the New Jersey site (p < 0.0001). Changing menopausal status was not a significant predictor of perceived stress. Conclusions: Self-reported stress decreased for most women as they transitioned across the midlife; changing menopausal status did not play a significant role after adjustment for age and sociodemographic factors. Future studies should explore the stress experience for women by racial/ethnic identity and demographics.

International burden of chronic kidney disease and secondary hyperparathyroidism: a systematic review of the literature and available data.

The international burden of secondary hyperparathyroidism (SHPT) is unknown, but it may be estimable through the available chronic kidney disease and SHPT literature. Structured reviews of biomedical literature and online data systems were performed for selected countries to ascertain recent estimates of the incidence, prevalence, and survival of individuals with CKD and SHPT. International societies of nephrology were contacted to seek additional information regarding available data. Estimates were abstracted from 35 sources reporting estimates of CKD in 25 countries. Population prevalence estimates of CKD stages 3-5 in adults ranged from approximately 1 to 9% (China, Mexico, resp.). Estimates of the population prevalence of maintenance dialysis therapy ranged from 79 per million population (pmp; China) to 2385 pmp (Japan); incidence rates ranged from 91 pmp (United Kingdom) to 349 pmp (United States). Prevalence of SHPT among stage 5D populations was highly variable and dependent upon the disease definition used. Among the few nations reporting, approximately 30-50% of stage 5D patients had serum parathyroid hormone levels >300 pg/mL. Reported incidence and prevalence estimates across the individual nations were variable, likely reflecting differing population demographics, risk factors, etiologies, and availability of treatment through all stages of CKD.

Nephrology care prior to end-stage renal disease and outcomes among new ESRD patients in the USA.

BACKGROUND: Longer nephrology care before end-stage renal disease (ESRD) has been linked with better outcomes. METHODS: We investigated whether longer pre-end-stage renal disease (ESRD) nephrology care was associated with lower mortality at both the patient and state levels among 443 761 incident ESRD patients identified in the USA between 2006 and 2010. RESULTS: Overall, 33% of new ESRD patients had received no prior nephrology care, while 28% had received care for >12 months. At the patient level, predictors of >12 months of nephrology care included having health insurance, white race, younger age, diabetes, hypertension and US region. Longer pre-ESRD nephrology care was associated with lower first-year mortality (adjusted hazard ratio = 0.58 for >12 months versus no care; 95% confidence interval 0.57-0.59), higher albumin and hemoglobin, choice of peritoneal dialysis and native fistula and discussion of transplantation options. Living in a state with a 10% higher proportion of patients receiving >12 months of pre-ESRD care was associated with a 9.3% lower relative mortality rate, standardized for case mix (R (2) = 0.47; P < 0.001). CONCLUSIONS: This study represents the largest cohort of incident ESRD patients to date. Although we did not follow patients before ESRD onset, our findings, both at the individual patient and state levels, reflect the importance of early nephrology care among those with chronic kidney disease.

Estimation of age- and sex-specific background human serum concentrations of PCDDs, PCDFs, and PCBs in the UMDES and NHANES populations.

Age- and sex-specific estimates of serum dioxin concentrations are important for comparisons among populations. However, such comparisons are problematic because populations have different age and sex structures and values are typically reported only in broad age ranges that are not comparable across studies. There are few studies that report congener-specific serum concentrations, and none that provide these by sex for age as a continuous function. We combined the NHANES 2003-2004 data with the University of Michigan Dioxin Exposure Study (UMDES) referent population 2005 data to achieve stable and accurate estimates of mean and quantiles of serum dioxins by sex over ages 18-85. Survey-weighted linear and quantile regression models were fitted on the combined data with the log-transformed congener concentration as outcome and age, sex, and data source as covariates. Formulas are provided to allow calculations of age- and sex-specific mean and quantile estimates over ages 18-85. For instance, the geometric mean, median, 75th percentile, and 95th percentile of serum TEQ for men aged 50 can be estimated, respectively, from the formulas as 18.33, 19.02, 22.60, and 30.37 pg g(-1) lipids among the Michigan general population, and as 15.71, 15.89, 22.60, and 29.90 pg g(-1) lipids among US non-Hispanic whites. These methods and results are useful for comparing the congener-specific human serum dioxin concentrations in any individual to the general population mean, median, 75th percentile, and 95th percentile, and for comparing the serum dioxin concentration in any group of interest to the US and the Michigan general populations.

Chronic kidney disease awareness among individuals with clinical markers of kidney dysfunction.

BACKGROUND AND OBJECTIVES: Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CKD awareness was assessed in 1852 adults with an estimated GFR <60 ml/min per 1.73 m(2) using 1999 to 2008 National Health and Nutrition Examination Survey data. CKD awareness was a "yes" answer to "Have you ever been told you have weak or failing kidneys?" Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. RESULTS: Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P < 0.01) than those without. Odds of CKD awareness increased with each additional manifested clinical marker of CKD (adjusted odds ratio, 1.3, P = 0.05). Nonetheless, 90% of individuals with two to four markers of CKD and 84% of individuals with ≥5 markers of CKD were unaware of their disease. CONCLUSIONS: Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications.

Surveillance of chronic kidney disease around the world: tracking and reining in a global problem.

In recent years, there has been a general recognition of the importance of tackling noncommunicable chronic diseases throughout the world and not just in developed nations. Chronic kidney disease (CKD) is increasingly recognized as a public health threat, based on its high prevalence, rising incidence, associated complications, and cost. It is imperative that nations develop screening and surveillance programs related to CKD. This article provides a global perspective on existing and emerging CKD surveillance efforts. A variety of programs are described, ranging from cross-sectional screening studies to determine CKD prevalence; targeted screening of high-risk populations presenting for voluntary testing; to more systematic surveillance within the scope of integrated health care systems in many developed nations. The choice of surveillance programs for many countries will depend on available resources and competing health care priorities. Integration with surveillance programs for other major chronic diseases such as diabetes, hypertension, and obesity is highly desirable and could be a key to the prevention of CKD. Finally, we propose the model of integrated health systems as one that is perhaps best suited to systematic, longitudinal surveillance of many chronic diseases, a model based on a national electronic health care record with linkage across primary care and hospital-based programs. Robust health education efforts and timely dissemination strategies will remain the key to the success of disease surveillance. It is gratifying to note that more and more countries are developing and adopting CKD surveillance programs as part of national disease prevention strategies.

Case report: the University of Michigan dioxin exposure study: a follow-up investigation of a case with high serum concentration of 2,3,4,7,8-pentachlorodibenzofuran.

CONTEXT: Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls that have toxic equivalency factors (TEFs) were measured in serum of 946 subjects in five Michigan counties. The study was motivated by concerns about human exposure to dioxin-contaminated sediments in the Tittabawassee River (TR). Most of the toxic equivalency in TR sediments is from two furan congeners, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-pentaCDF). CASE PRESENTATION: The individual with the highest adjusted (for age, age squared, and body mass index) serum level of 2,3,4,7,8-pentaCDF in the study (42.5 ppt) reported a unique history of raising cattle and vegetables in the floodplain of the TR. Interviews and serum samples were obtained from the index case and 15 other people who ate beef and vegetables raised by the index case. 2,3,4,7,8-pentaCDF in beef lipid was estimated to have been more than three orders of magnitude greater than background (1,780 vs. 1.1 ppt). The mean, median, and 95th percentile for serum 2,3,4,7,8-pentaCDF in the study control population were 6.0, 5.4, and 13.0 ppt, respectively, and were 9.9, 8.4, and 20.5 ppt among beef and vegetable consumers, respectively. Back extrapolation for the index case suggests that his increase in serum concentration of 2,3,4,7,8-pentaCDF above background may have been as high as 146 ppt. DISCUSSION: Consumption of beef and/or vegetables raised on dioxin-contaminated soil may be an important completed pathway of exposure. RELEVANCE TO PUBLIC HEALTH PRACTICE: Animals and crops should not be raised for human consumption in areas contaminated with dioxins.

Establishing a national chronic kidney disease surveillance system for the United States.

Despite the recognized importance of chronic kidney disease (CKD), the United States currently lacks a comprehensive, systematic surveillance program that captures and tracks all aspects of CKD in the population. As part of its CKD Initiative, the Centers for Disease Control and Prevention (CDC) funded two teams to jointly initiate the development of a CKD surveillance system. Here, we describe the process and methods used to establish this national CDC CKD Surveillance System. The major CKD components covered include burden (incidence and prevalence), risk factors, awareness, health consequences, processes and quality of care, and health system capacity issues. Goals include regular reporting of the data collected, plus development of a dynamic project web site and periodic issuance of a CKD fact sheet. We anticipate that this system will provide an important foundation for widespread efforts toward primary prevention, earlier detection, and implementation of optimal disease management strategies, with resultant increased awareness of CKD, decreased rates of CKD progression, lowered mortality, and reduced resource utilization. Final success will be measured by usage, impact, and endorsement.