Search

Objective: Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.Research Design and Methods: Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women and <1.5 mg/dL for men) and eGFR categories: likely safe, ≥45 mL/min/1.73 m(2); contraindicated, <30 mL/min/1.73 m(2); and indeterminate, 30-44 mL/min/1.73 m(2)). Different eGFR equations were used: four-variable MDRD, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl). Diabetes was defined by self-report or A1C ≥6.5% (48 mmol/mol). We used logistic regression to identify populations for whom metformin was likely safe adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S. adult population.Results: Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8 [4.27-51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR <30 mL/min/1.73 m(2). All estimating equations expanded the population of individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to 834,800 (CG). All equations identified larger populations with eGFR 30-44 mL/min/1.73 m(2), for whom metformin safety is indeterminate, ranging from 784,700 (CKD-EPIcr) to 1,636,000 (CG).Conclusions: The use of eGFR or CrCl to determine metformin eligibility instead of sCr can expand the adult population with diabetes for whom metformin is likely safe, particularly among non-Hispanic blacks and men. [ABSTRACT FROM AUTHOR]

Background Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache. Objective To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids. Methods Participants with MOH who were using opioids were randomized via computer-generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double-blind, parallel groups study. Before randomization participants completed a 4-week baseline headache diary. During treatment, headache diary data collection continued and participants attended 4 study visits during which quantitative sensory testing was performed. Blood samples for immune biomarker analyses were collected before and after treatment in a subgroup of participants. Results Thirty-four participants were randomized, 13 of 15 randomized to ibudilast and 17 of 19 randomized to placebo completed treatment. Ibudilast was generally well-tolerated with mild, transient nausea reported as the most common adverse event (66.7% vs 10.5% in placebo group). Results are shown as mean (SD). At the end of treatment no differences in the primary outcome average daily headache index (placebo 62 [44] vs ibudilast 77 [72] groups, difference −15, CI −65 to 35 h × numerical rating scale), or secondary outcomes headache frequency (placebo 23 [8.1] vs ibudilast 24.5 [6.2], difference −1.5, CI −7.7 to 4.8 days/month) and opioid intake (placebo 20.6 [43] vs ibudilast 19 [24.3], difference 1.6, CI −31.5 to 34.8 mg morphine equivalent) were observed between placebo and ibudilast groups. Conclusions Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether macronutrient intake differs by awareness of glycemic status among people with diabetes and prediabetes. RESEARCH DESIGN AND METHODS We used 24-h dietary recall and other data from 3,725 nonpregnant adults with diabetes or prediabetes aged ≥20 years from the morning fasting sample of the 2005-2010 National Health and Nutrition Examination Survey. Diabetes and prediabetes awareness were self-reported; those unaware of diabetes and prediabetes were defined by fasting plasma glucose (FPG) ≥126 mg/dL or HbA1c S6.5% and FPG 100-125 mg/dL or HbA1c of 5.7%-6.4%, respectively. Components of nutrient intake on a given day assessed were total calories, sugar, carbohydrates, fiber, protein, fat, and total cholesterol, stratified by sex and glycemic status awareness. Estimates of nutrient intake were adjusted for age, race/ethnicity, education level, BMI, smoking status, and family history of diabetes. RESULTS Men with diagnosed diabetes consumed less sugar (mean 86.8 vs. 116.8 g) and carbohydrates (mean 235.0 vs. 262.1 g) and more protein (mean 92.3 vs. 89.7 g) than men with undiagnosed diabetes. Similarly, women with diagnosed diabetes consumed less sugar (mean 79.1 vs. 95.7 g) and more protein (mean 67.4 vs. 56.6 g) than women with undiagnosed diabetes. No significant differences in macronutrient intake were found by awareness of prediabetes. All participants, regardless of sex or glycemic status, consumed on average less than the American Diabetes Association recommendations for fiber intake (i.e., 14 g/1,000 kcal) and slightly more saturated fat than recommended (>10% of total kcal). CONCLUSIONS Screening and subsequent knowledge of glycemic status may favorably affect some dietary patterns for people with diabetes. [ABSTRACT FROM AUTHOR]

Background: Diet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAEes) with CKD; and socio-demographic and clinical correlates of NAEes. Methods: Among 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999–2004, we assessed dietary acid by estimating NAEes from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73m2 using the MDRD equation. We tested the association of NAEes with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression. Results: Median regression results (β per quintile) indicated that adults aged 40–60 years (β [95% CI] = 3.1 [0.3–5.8]), poverty (β [95% CI] = 7.1 [4.01–10.22]), black race (β [95% CI] = 13.8 [10.8–16.8]), and male sex (β [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAEes. Higher levels of NAEes compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20–2.05]). We observed a trend toward greater NAEes being associated with higher risk of low eGFR, which persisted after adjustment for confounders. Conclusion: Higher NAEes is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAEes. DAL may be an important target for future interventions in populations at high risk for CKD. [ABSTRACT FROM AUTHOR]

During 2010, approximately 6,091 persons aged ≥18 years in Puerto Rico were living with end-stage renal disease (ESRD) (i.e., kidney failure that requires regular dialysis or kidney transplantation for survival). This included 1,462 persons who began treatment for ESRD in 2010. Diabetes is the leading cause of ESRD in Puerto Rico, accounting for 66% of new cases in adults, followed by hypertension, which accounts for 15% of the cases. Although the number of adults initiating ESRD treatment (i.e., dialysis or kidney transplantation) in Puerto Rico each year who have diabetes listed as a primary cause (ESRD-D) has increased since 1996, ESRD-D incidence among adults with diagnosed diabetes has not shown a consistent trend. To assess recent trends in ESRD-D incidence among adults aged ≥18 years in Puerto Rico with diagnosed diabetes and to further examine trends by age group and sex, CDC analyzed 1996-2010 data from the U.S. Renal Data System (USRDS) and the Behavioral Risk Factor Surveillance System (BRFSS). After increasing in the late 1990s, ESRD-D incidence decreased during the 2000s among adult men and among persons aged 18-44 years with diagnosed diabetes in Puerto Rico. Throughout the period, ESRD-D incidence among adult women and among persons aged 45-64 and ≥75 years with diagnosed diabetes did not show a consistent trend, and ESRD-D incidence among persons aged 65-74 years with diagnosed diabetes increased. Increased awareness of the risk factors for kidney disease and implementation of effective interventions to prevent or delay kidney disease among persons with diagnosed diabetes might decrease ESRD incidence in Puerto Rico, particularly among women and older persons. [ABSTRACT FROM AUTHOR]

The article presents an assessment of recent trends in end-stage renal disease (ESRD) incidence among adults with diagnosed diabetes in Puerto Rico. It explains how ESRD incidence rates were calculated for the U.S. Renal Data System (USRDS). It relates the increase in the number of adults aged 18 or more who began ESRD treatment during the 1996-2010 period. It discusses trends of ESRD incidence by age group and sex.

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. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Using a nationally representative sample of the civilian noninstitutionalized U.S. population, we estimated prediabetes prevalence and its changes during 1999-2010.Research Design and Methods: Data were from 19,182 nonpregnant individuals aged ≥ 12 years who participated in the 1999-2010 National Health and Nutrition Examination Surveys. We defined prediabetes as hemoglobin A1c (A1C) 5.7 to <6.5% (39 to <48 mmol/mol, A1C5.7) or fasting plasma glucose (FPG) 100 to <126 mg/dL (impaired fasting glucose [IFG]). We estimated the prevalence of prediabetes, A1C5.7, and IFG for 1999-2002, 2003-2006, and 2007-2010. We calculated estimates age-standardized to the 2000 U.S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI. Participants with self-reported diabetes, A1C ≥ 6.5% (≥ 48 mmol/mol), or FPG ≥126 mg/dL were included.Results: Among those aged ≥ 12 years, age-adjusted prediabetes prevalence increased from 27.4% (95% CI 25.1-29.7) in 1999-2002 to 34.1% (32.5-35.8) in 2007-2010. Among adults aged ≥ 18 years, the prevalence increased from 29.2% (26.8-31.8) to 36.2% (34.5-38.0). As single measures among individuals aged ≥ 12 years, A1C5.7 prevalence increased from 9.5% (8.4-10.8) to 17.8% (16.6-19.0), a relative increase of 87%, whereas IFG remained stable. These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates.Conclusions: During 1999-2010, U.S. prediabetes prevalence increased because of increases in A1C5.7. Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Using a nationally representative sample of the civilian noninstitutionalized U.S. population, we estimated prediabetes prevalence and its changes during 1999-2010. RESEARCH DESIGN AND METHODS--Data were from 19,182 nonpregnant individuals aged ≥12 years who participated in the 1999-2010 National Health and Nutrition Examination Surveys. We defined prediabetes as hemoglobin A1c (A1C) 5.7 to <6.5% (39 to <48 mmol/mol, A1C5.7) or fasting plasma glucose (FPG) 100 to <126 mg/dL (impaired fasting glucose [IFG]). We estimated the prevalence of prediabetes, A1C5.7, and IFG for 1999-2002, 2003-2006, and 2007-2010. We calculated estimates age-standardized to the 2000 U.S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI. Participants with self-reported diabetes, A1C ≥6.5% (≥48 mmol/mol), or FPG ≥126 mg/dL were included. RESULTS--Among those aged ≥ 12 years, age-adjusted prediabetes prevalence increased from 27.4% (95% CI 25.1-29.7) in 1999-2002 to 34.1% (32.5-35.8) in 2007-2010. Among adults aged ≥18 years, the prevalence increased from 29.2% (26.8-31.8) to 36.2% (34.5-38.0). As single measures among individuals aged ≥12 years, A1C5.7 prevalence increased from 9.5% (8.4-10.8) to 17.8% (16.6-19.0), a relative increase of 87%, whereas IFG remained stable. These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates. CONCLUSIONS--During 1999-2010, U.S. prediabetes prevalence increased because of increases in A1C5.7. Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts. [ABSTRACT FROM AUTHOR]

The current models for colorectal cancer (CRC) are essentially linear in nature with a sequential progression from adenoma through to carcinoma. However, these views of CRC development do not explain the full body of published knowledge and tend to discount environmental influences. This paper proposes that CRC is a cellular response to prolonged exposure to cytotoxic agents (e.g., free ammonia) as key events within a sustained high-risk colonic luminal environment. This environment is low in substrate for the colonocytes (short chain fatty acids, SCFA) and consequently of higher pH with higher levels of free ammonia and decreased mucosal oxygen supply as a result of lower visceral blood flow. All of these lead to greater and prolonged exposure of the colonic epithelium to a cytotoxic agent with diminished aerobic energy availability. Normal colonocytes faced with this unfavourable environment can transform into CRC cells for survival through epigenetic reprogramming to express genes which increase mobility to allow migration and proliferation. Recent data with high protein diets confirm that genetic damage can be increased, consistent with greater CRC risk. However, this damage can be reversed by increasing SCFA supply by feeding fermentable fibre as resistant starch or arabinoxylan. High protein, low carbohydrate diets have been shown to alter the colonic environment with lower butyrate levels and apparently greater mucosal exposure to ammonia, consistent with our hypothesis. Evidence is drawn from in vivo and in vitro genomic and biochemical studies to frame experiments to test this proposition. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the relationship between access to health care and diabetes control. RESEARCH DESIGN AND METHODS--Using data from the National Health and Nutrition Examination Survey, 1999--2008, we identified 1,221 U.S. adults (age 18--64 years) with self-reported diabetes. Access was measured by current health insurance coverage, number of times health care was received over the past year, and routine place to go for health care. Diabetes control measures included the proportion of people with A1C >9%, blood pressure ≥140/90 mmHg, and non-HDL cholesterol ≥130 mg/dL. RESULTS--An estimated 16.0% of known diabetic adults were uninsured. Diabetes control profiles were worse among uninsured than among insured persons (A1C >9% [34.1 vs. 16.5%, P = 0.002], blood pressure ≥140/90 mmHg [31.8 vs. 22.8%, P < 0.05], and non-HDL cholesterol ≥130 mg/dL [67.1 vs. 65.4%, P = 0.7]). Compared with insured persons, uninsured persons were more likely to have A1C >9% (multivariate-adjusted odds ratio 2.4 [95% CI 1.2--4.7]). Compared with those who reported four or more health care visits in the past year, those who reported no health care visits were more likely to have A1C.9%(5.5 [1.2--26.3]) and blood pressure ≥140/90 mmHg (1.9 [1.1--3.4]). CONCLUSIONS--In people with diabetes, lack of health care coverage is associated with poor glycemic control. In addition, low use of health care service is associated with poor glucose and blood pressure control. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The intradermal capsaicin model of neuropathic pain has been previously developed and used in healthy volunteers. • Few previous studies have used this model in pain patients. WHAT THIS STUDY ADDS • We have compared the response to intradermal capsaicin in the painful and nonpainful legs of patients with unilateral sciatica and compared these with healthy, pain-free control subjects. Pain and hyperalgesia responses were enhanced in both legs of patients with unilateral sciatica compared with healthy controls. The time course of hyperalgesia was different in sciatica patients, demonstrating a slower and larger evolution. • Qualitative and quantitative differences between pain patients and healthy controls suggest that the use of a neuropathic pain model such as intradermal capsaicin to screen for novel antineuropathic agents might be superior in patients with pre-existing neuropathic pain syndromes. AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. [ABSTRACT FROM AUTHOR]

The prevalence of cardiovascular disease (CVD) risk factors among youth with type 1 diabetes is high and associated with age, gender, and race/ethnicity. It has also been shown that youth with type 1 diabetes often do not follow dietary recommendations. The objective of this cross-sectional observational study was to explore the association of sugar-sweetened and diet beverage intake with A1c, plasma lipids, adiponectin, leptin, systolic, and diastolic blood pressure in youth with type 1 diabetes. We examined data from 1,806 youth age 10-22 years with type 1 diabetes, of which 22% were minority (10% Hispanic, 8% African Americans, 4% other races) and 48% were female. Sugar-sweetened beverage, diet beverage, and mineral water intake was assessed with a food frequency questionnaire. After adjustment for socio-demographic and clinical covariates, physical activity and total energy intake, high sugar-sweetened beverage intake (at least one serving per day vs. none), was associated with higher levels of total cholesterol, LDL cholesterol, and plasma triglycerides, but not with A1c. High diet beverage intake was associated with higher A1c, total cholesterol, LDL cholesterol, and triglycerides. These associations were partially confounded by body mass index, saturated fat and total fiber intake. High sugar-sweetened beverage intake may have an adverse effect on CVD risk in youth with type 1 diabetes. Diet beverage intake may be a marker of unhealthy lifestyle which, in turn, is associated with worse metabolic control and CVD risk profile in these youth. Youth with diabetes should be encouraged to minimize sugar-sweetened beverage intake. [ABSTRACT FROM AUTHOR]

Background: Little is known about disability in early-stage chronic kidney disease (CKD). Study Design: Cross-sectional national survey (National Health and Nutrition Examination Survey 1999-2006). Setting & Participants: Community-based survey of 16,011 noninstitutionalized US civilian adults (aged ≥20 years). Predictor: CKD, categorized as no CKD, stages 1 and 2 (albuminuria and estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m²), and stages 3 and 4 (eGFR, 15-59 mL./min/1.73 m²). Outcome: Self-reported disability, defined by limitations in working, walking, and cognition and difficulties in activities of daily living (ADL), instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Measurements: Albuminuria and eGFR assessed from urine and blood samples; disability, demographics, access to care, and comorbid conditions assessed using a standardized questionnaire. Results: Age-adjusted prevalence of reported limitations generally was significantly greater with CKD: for example, difficulty with ADL was reported by 17.6%, 24.7%, and 23.9% of older (≥65 years) and 6.8%, 11.9%, and 11.0% of younger (20-64 years) adults with no CKD, stages 1 and 2, and stages 3 and 4, respectively. CKD also was associated with greater reported limitations and difficulty in other activities after age adjustment, including instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Other demographics, socioeconomic status, and access to care generally only slightly attenuated the observed associations, particularly in older individuals; adjustment for cardiovascular disease, arthritis, and cancer attenuated most associations such that statistical significance no longer was achieved. Limitations: Inability to establish causality and possible unmeasured confounding. Conclusion: CKD is associated with a higher prevalence of disability in the United States. Age and other comorbid conditions account for most, but not all, of this associations. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To compare the prevalence of prediabetes using A1C, fasting plasma glucose (FPG), and oral glucose tolerance test (OGTT) criteria, and to examine the degree of agreement between the measures. RESEARCH DESIGN AND METHODS--We used the 2005-2008 National Health and Nutrition Examination Surveys to classify 3,627 adults aged ≥18 years without diabetes according to their prediabetes status using A1C, FPG, and OGTT. We compared the prevalence of prediabetes according to different measures and used conditional probabilities to examine agreement between measures. RESULTS--In 2005-2008, the crude prevalence of prediabetes in adults aged ≥18 years was 14.2% for A1C 5.7-6.4% (A1C5.7), 26.2% for FPG 100-125 mg/dL (IFG100), 7.0% for FPG 110-125 mg/dL (IFG110), and 13.7% for OGTT 140-199 mg/dL (IGT). Prediabetes prevalence varied by age, sex, and race/ethnicity, and there was considerable discordance between measures of prediabetes. Among those with [GT, 58.2, 23.4, and 32.3% had IFG100, IFG110, and A1C5.7, respectively, and 67.1% had the combination of either A1C5.7 or IFG100. CONCLUSIONS--The prevalence of prediabetes varied by the indicator used to measure risk; there was considerable discordance between indicators and the characteristics of individuals with prediabetes. Programs to prevent diabetes may need to consider issues of equity, resources, need, and efficiency in targeting their efforts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We examined ranges of A1C useful for identifying persons at high risk for diabetes prior to preventive intervention by conducting a systematic review. From 16 included studies, we found that annualized diabetes incidence ranged from 0.1% at A1C <5.0% to 54.1% at A1C ≥6.1%. Findings from 7 studies that examined incident diabetes across a broad range of A1C categories showed 1) risk of incident diabetes increased steeply with A1C across the range of 5.0 to 6.5%; 2) the A1C range of 6.0 to 6.5% was associated with a highly increased risk of incident diabetes, 25 to 50% incidence over 5 years; 3) the A1C range of 5.5 to 6.0% was associated with a moderately increased relative risk, 9 to 25% incidence over 5 years; and 4) the A1C range of 5.0 to 5.5% was associated with an increased incidence relative to those with A1C <5%, but the absolute incidence of diabetes was less than 9% over 5 years. Our systematic review demonstrated that A1C values between 5.5 and 6.5% were associated with a substantially increased risk for developing diabetes. [ABSTRACT FROM AUTHOR]

Micro/nanoporous osmotic pump tablets coated with cellulose acetate containing polyvinylpyrolidone (PVP) as pore formers were fabricated. Propranolol hydrochloride was used as a model drug in this study. Formulation optimization based on USP 31 requirements was conducted following a central composite design using a two-level factorial plan involving two membrane variables (pore former and coating levels). Effect of molecular weight of pore former (PVP K30 and PVP K90) was also evaluated. Responses of drug release to the variables were analyzed using statistical software (MINITAB 14). Scanning electron microscopy and atomic force microscopy showed that the pores formed by PVP. The drug release was dependent on the molecular weight and concentration of PVP and the level of coating. The results showed that acceptable 12-h profile could be achieved with only specific range of PVP K30-containing membrane at the defined membrane thickness. However, satisfactory 24-h profile could be accomplished by both PVP K30 and PVP K90-containing membrane at the range and membrane thickness tested. Preparation and testing of the optimized formulation showed a good correlation between predicted and observed values. [ABSTRACT FROM AUTHOR]

Abstract: Background: Secular trends over 34 years (1965–1998) in overall and cause-specific mortality were examined in 4623 Pima Indians ≥35 years old. Methods: The underlying and contributing causes of the 1363 deaths were determined from a review of all available clinical records; 540 of the deaths occurred in the 2528 nondiabetic participants and 823 in the 2095 participants who had diabetes during all or part of the study period. Age/sex-adjusted death rates were calculated across four 8.5-year time intervals. Results: In the nondiabetic participants, the rate of death from natural causes declined gradually over time (20.4, 17.3, 17.3, and 16.0 deaths per 1000 persons/year; P=.11); deaths from ischemic heart disease (IHD) were uncommon (n=22), and the rate did not change appreciably, remaining as the fifth leading natural cause of death. In the diabetic participants, the rate of death from natural causes was unchanged over time, but the rate of death from IHD (n=141) increased nearly twofold (3.3, 4.2, 6.4, and 6.4 deaths per 1000 persons/year; P<.01), becoming the leading cause of death in the third and fourth time intervals. Conclusions: The rate of death from IHD remained stable in nondiabetic Pima Indians but increased among those with diabetes. This finding suggests that, in the absence of diabetes, the underlying susceptibility to IHD in this population has not changed. [Copyright &y& Elsevier]

Context: Prevalence of obesity in the United States has increased dramatically in recent decades, but the magnitude of change in cardiovascular disease (CVD) risk factors among the growing proportion of overweight and obese Americans remains unknown. Objective: To examine 40-year trends in CVD risk factors by body mass index (BMI) groups among US adults aged 20 to 74 years. Design, Setting, and Participants: Analysis of 5 cross-sectional, nationally representative surveys: National Health Examination Survey (1960-1962); National Health and Nutrition Examination Survey (NHANES) I (1971-1975), II (1976-1980), and III (1988-1994); and NHANES 1999-2000. Main Outcome Measures: Prevalence of high cholesterol level (≥240 mg/dL [≥6.2 mmol/L] regardless of treatment), high blood pressure (≥140/90 mm Hg regardless of treatment), current smoking, and total diabetes (diagnosed and undiagnosed combined) according to BMI group (lean, <25; overweight, 25-29; and obese, ≥30). Results: The prevalence of all risk factors except diabetes decreased over time across all BMI groups, with the greatest reductions observed among overweight and obese groups. Compared with obese persons in 1960-1962, obese persons in 1999-2000 had a 21-percentage-point lower prevalence of high cholesterol level (39% in 1960-1962 vs 18% in 1999-2000), an 18-percentage-point lower prevalence of high blood pressure (from 42% to 24%), and a 12-percentage-point lower smoking prevalence (from 32% to 20%). Survey × BMI group interaction terms indicated that compared with the first survey, the prevalence of high cholesterol in the fifth survey had fallen more in obese and overweight persons than in lean persons (P<.05). Survey × BMI changes in blood pressure and smoking were not statistically significant. Changes in risk factors were accompanied by increases in lipid-lowering and antihypertensive medication use, particularly among obese persons. Total diabetes prevalence was stable within BMI groups over time, as nonsignificant 1- to 2-percentage-point increases occurred between 1976-1980 and 1999-2000. Conclusions: Except for diabetes, CVD risk factors have declined considerably over the past 40 years in all BMI groups. Although obese persons still have higher risk factor levels than lean persons, the levels of these risk factors are much lower than in previous decades. [ABSTRACT FROM AUTHOR]

On March 20, 2015, 30 days after the most recent confirmed Ebola Virus Disease (Ebola) patient in Liberia was isolated, Ebola was laboratory confirmed in a woman in Monrovia. The investigation identified only one epidemiologic link to Ebola: unprotected vaginal intercourse with a survivor. Published reports from previous outbreaks have demonstrated Ebola survivors can continue to harbor virus in immunologically privileged sites for a period of time after convalescence. Ebola virus has been isolated from semen as long as 82 days after symptom onset and viral RNA has been detected in semen up to 101 days after symptom onset. One instance of possible sexual transmission of Ebola has been reported, although the accompanying evidence was inconclusive. In addition, possible sexual transmission of Marburg virus, a filovirus related to Ebola, was documented in 1968. This report describes the investigation by the Government of Liberia and international response partners of the source of Liberia's latest Ebola case and discusses the public health implications of possible sexual transmission of Ebola virus. Based on information gathered in this investigation, CDC now recommends that contact with semen from male Ebola survivors be avoided until more information regarding the duration and infectiousness of viral shedding in body fluids is known. If male survivors have sex (oral, vaginal, or anal), a condom should be used correctly and consistently every time. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion The ideal dosing weight metric for enoxaparin remains elusive. Dosing remains focused on actual body weight, which may inadvertently increase the risk of bleeding in those with obesity, or ideal weight, which may underdose those with obesity. Our aim was to determine the optimal obesity‐adjusted enoxaparin dosing weight.Multisite retrospective data were collected over a 2.0‐year period for those with minimum 48 h of in‐hospital twice‐daily enoxaparin and factor anti‐Xa level 3–5 h postdose (n = 220). Multiple linear regression calculated the associated variance between a range of nominal dosing weights and factor anti‐Xa levels, adjusted for renal function. Dosing weights were calculated as ideal body weight (IBW) and then adjusted for increasing percentages of weight above IBW, i.e. IBW + 10% above IBW, IBW + 20% etc. up to actual body weight. A similar approach was used for lean body weight (LBW).For body mass index ≥30 kg/m2 optimal variance explained by dosing weight metrics was at IBW + 40% (23%) and similarly for LBW + 40% (23%). Using actual body weight (ABW) had lowest associated variance with factor anti‐Xa levels (18%) followed by unadjusted IBW (13%) or unadjusted LBW (19%). In those with body mass index <30 kg/m2 there was similar associated variance in the ranges of IBW + 20–50% and LBW 10–40% (21%).Compared to IBW + 40% or LBW + 40% use of ABW to calculate dose was poorly associated with factor anti‐Xa levels, as was IBW or LBW. IBW + 40% and LBW + 40% require further study as a dosing weight metric and may provide a more consistent factor anti‐Xa response in those with obesity. [ABSTRACT FROM AUTHOR]

• An accurate and precise LC–MS/MS method was developed to quantify opioid analgesics. • This method is capable to quantify eight analytes simultaneously. • The method is applicable to plasma and whole blood collected via venepuncture or volumetric absorptive micro sampling (VAMS) devices. • This method could help to set the base practice for opioid Therapeutic Drug Monitoring in older patients. A range of opioids are commonly prescribed to manage chronic pain, but individual patient responses vary greatly, especially in older populations. One source of that variability are differences in absorption, metabolism and excretion, i.e. pharmacokinetics. Blood, plasma and serum concentrations of opioids allow that variability to be quantified and may be used to optimise opioid dosing. As an aid to that process, there is an unmet need to rapidly quantify several opioids and their metabolites in a single analytical method. To develop a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of tramadol, oxycodone, fentanyl and their major metabolites in various human matrices. Sample preparation involved adding three deuterated internal standards followed by protein precipitation with 100 % acetonitrile, evaporation and reconstitution. Separation of analytes via LC was achieved on a reversed phase column via binary gradient elution using 0.005 % formic acid in water and 100 % acetonitrile as mobile phases. Analytes were detected via MS/MS with multiple reaction monitoring (MRM). The method was accurate with the inter-day and intra-day accuracy of quality control samples (QCs) below 15 %. It was also precise with inter-day and intra-day coefficient of variation below 15 %. The lower limit of quantification (LLOQ) was 0.2 ng/mL for all analytes except tramadol and its metabolites, where the LLOQ was 10 ng/mL. Recovery was greater than 88 % for all analytes, except for O-desmethyltramadol (81 %). Analytes were stable over four freeze-thaw cycles, for 24 h on the bench top and for 24 h post-preparation. The inter- and intra-day variability of concentrations determined in blood and plasma were within 84–124%, whereas the inter- and intra-day variability for blood samples prepared using volumetric absorptive micro-sampling (VAMS) compared to those prepared from whole blood ranged between 83–122%. A LC–MS/MS method is described that is able to accurately and precisely quantify a number of commonly prescribed opioids and their major metabolites in plasma and whole blood, including whole blood collected using VAMS. [ABSTRACT FROM AUTHOR]