Indwelling peritoneal catheters in patients with cirrhosis and refractory ascites.

BACKGROUND: The prevalence of spontaneous bacterial peritonitis (SBP) in hospitalised cirrhotics with ascites is 10-30%. Treatment for refractory ascites includes paracenteses, transjugular intrahepatic portosystemic shunt or drain placement; the latter is discouraged due to a perceived infection risk. AIM: This study aimed to evaluate the risk of bacterial peritonitis (BP) with peritoneal drains in patients with Child-Pugh class B or C cirrhosis and determine their impact on survival. METHODS: We conducted a retrospective review of end-stage liver disease (ESLD) patients with non-malignant, refractory ascites who had peritoneal drains placed for ≥3 days at Loyola University between 1999 and 2009. Cell counts were performed at drain placement and within 72 h. BP was defined as ascitic polymorphonuclear neutrophils >250/mm(3) . Univariate analysis assessed the association between demographics, laboratory markers and development of BP. Kaplan-Meier curve estimates by infection were constructed and survival distributions were compared using log-rank statistic. RESULTS: There were 227 drain placements during the study period. Twenty-two per cent were diagnosed with BP (12% had SBP at drain placement; 10% developed BP within 72 h). There was no association between BP and baseline characteristics. Patients who developed BP within 72 h of drain placement had 50% mortality at 5 months compared with 50 months in those without infection (log-rank P ≤ 0.003). CONCLUSION: In ESLD patients who received an indwelling peritoneal catheter, there was 10% risk of developing BP and significant mortality increase. Though placing drains is not the mainstay of treatment for refractory ascites, we confirm the theoretical adverse risk of peritoneal drains on infection and survival in cirrhotics.

Assessment of the Relationship Between Inflammation and Glomerular Filtration Rate.

Background: Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs). Objective: To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-ß, correlate with various CKD stages. Methods: One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA. Results: By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-ß correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases. Conclusions: Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.

Contexte: L'insuffisance rénale chronique (IRC) est un problème de santé mondial. Une thérapie de remplacement rénal est nécessaire au fur et à mesure que la maladie évolue vers les stades terminaux. Mais, en définitive, le meilleur traitement reste la transplantation. La réduction de la fonction rénale a été associée à un état inflammatoire associé à l'IRC primaire; une association observée aussi chez les receveurs d'une greffe de rein. Objectif: Déterminer la façon dont les concentrations sériques de certaines cytokines, notamment IL-2, IL-8, IL-22, IL-17a, IFN-γ, IL-4 et TGF-ß, corrèlent avec divers stades de l'IRC. Méthodologie: Ont été inclus dans l'étude 141 receveurs d'une greffe rénale âgés de 18 à 75 ans, 112 donneurs vivants de rein, 37 personnes atteintes d'IRC (PGIRC+3) et 76 personnes en bonne santé (PGen santé). Les sujets ont été regroupés en fonction de leur débit de filtration glomérulaire (DFGe) et de leur taux de cytokines en circulation, quantifiés préalablement par ELISA. Résultats: Une analyse de régression linéaire a servi à établir la relation entre chaque cytokine et le DFGe. Dans la population étudiée, une corrélation positive a été observée entre TGF-ß et le DFGe, sauf chez les individus sains. Dans tous les cas, la corrélation s'est avérée négative entre le DFGe et les taux d'IL-8 et d'IL-17a. Conclusion: Il reste à déterminer prospectivement si ces cytokines (IL-8 et IL-17a) pourraient être utilisées comme biomarqueurs inflammatoires pour indiquer la progression de l'IRC, quelle que soit la population.

Biotin supplementation causes erroneous elevations of results in some commercial serum 25-hydroxyvitamin d (25OHD) assays.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants' performance of specific methods for 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D). DEQAS occasionally circulates samples containing high levels of substances found in certain clinical situations e.g. 25-OHD2, 24,25-(OH)2D3, hypertriglyceridemia. The increased availability and use of health supplements containing biotin has led to case reports of assay interference in methods utilizing a biotin-streptavidin detection system. In October 2018, DEQAS included a serum sample (545) containing exogenous biotin (concentration =586 µg/L) which was analyzed by a total of 683 laboratories using 35 different methods. The same serum sample (544) without exogenous biotin was also included in the 5-sample set. All methods (760 laboratories) performed satisfactorily on sample 544 giving an All-Laboratory Trimmed Mean = 50.2 ± 6.5 nmol/L (±SD, CV = 12.9 %). The target value for this sample 544 (& 555) was 47.4 nmol/L as determined by Centers for Disease Control and Prevention (CDC) Atlanta, Georgia using their LC-MS/MS reference method. In contrast, #545 containing the exogenous biotin was reported by only 683 laboratories and gave an All-Laboratory Trimmed Mean = 66.8 ± 37.6 nmol/L (±SD, CV = 56.3 %). As expected, LC-MS/MS methods (143 labs) reported similar results for both 544 = 48.9 ± 4.4 nmol/L (±SD) and 545 = 48.3 ± 4.5 nmol/L (±SD) showing that assays involving chromatographic steps are unaffected by the presence of biotin. Several of the antibody-based assays including Abbott Architect, DiaSorin Liaison, Beckman Unicel and Siemens Centaur are also unaffected by the addition of biotin. Two assays, IDS-iSYS and Roche Total 25OHD, both of which use biotin-streptavidin, exhibit biotin interference yielding values with a significant positive bias for 545 of 102.6 nmol/L ± 78.7 nmol/L (±SD) and 517.8 nmol/L ± 209.8 nmol/L (±SD) respectively. Interestingly, the failure to report sample 545 data from 77 laboratories is due solely to those running Roche Total 25OHD or Roche Vitamin D Total II assays. Given the prevalence of the adversely affected assays (25 % of DEQAS users) and the high volume of 25OHD testing, clinicians using these assays should, where possible, only measure 25OHD when patients are off biotin.

Estimating uncertainty of target values for DEQAS serum materials.

The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single 'target value' for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory's assay would be regarded as traceable, i.e. standardized, to the NIST RMP.

External Quality Assessment of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) assays.

The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2D3. Several studies have also suggested that a high 25-hydroxyvitamin D3(25-OHD3):24,25(OH)2D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results. The international External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) was set up in 1989. In 2013 DEQAS became an accuracy based EQA for 25-OHD with 'target values' assigned by the National Institute of Standards and Technology (NIST) Reference Measurement Procedure (RMP). A pilot scheme for serum 24,25(OH)2D3 was started in 2015 and participants were asked to measure the metabolite on each of the 5 samples sent out for 25-OHD. Inter-laboratory agreement was poor but this may reflect methodological differences, in particular different approaches to assay standardization. An important potential contribution to reducing variability among assays was the development by NIST of a 24,25(OH)2D3 RMP and its use in assigning values to SRMs 972a, 2973 and 2971, supported by the NIH Office of Dietary Supplements (ODS) as part of the Vitamin D Standardization Program (VDSP) effort.

Issues related to modeling the body mass index-mortality association: the shape of the association and the effects of smoking status.

Research on the relationship between body mass index (BMI) and mortality has led to conflicting results; a lack of agreement about how to adjust for confounders, such as smoking status, has added to the problem. Complicating such analyses is the fact that the BMI-mortality association is not a symmetric quadratic relationship; the distribution tends to be skewed to the right, causing the optimal BMI--where mortality is at a minimum--to be overestimated. One way to overcome this problem is by transformation of the BMI distribution to normality. The authors suggest several approaches for doing so, including the use of 1/BMI, or lean body mass index, instead of BMI in modeling. Data sets on 50 cohorts from approximately 30 international studies were used to examine the association (direct, inverse, quadratic or none) between BMI and mortality and to investigate the possible interaction of smoking status. Of the 50 cohorts, 36 showed a quadratic association between BMI and mortality, 10 showed no association and 1 showed a direct association between lean BMI and mortality. Only three cohorts showed a significant interaction between BMI and smoking, which was approximately what one would expect from a 5% significance test, even if no interaction existed. The association between BMI and mortality is not changed when smoking status is ignored in a model or when data on smokers are excluded from analysis. The methodology used in this study could be extended to look for other interactions.

Hypertension in Mexico and among Mexican Americans: prevalence and treatment patterns.

Increased social and economic integration across the US-Mexican borders has led to important new developments in public health. Lower levels of cardiovascular mortality have been observed among Mexican Americans (MAs) although few direct comparisons have been undertaken with Mexico. Using survey data in the respective countries we examined blood pressure (BP) levels, hypertension prevalence and patterns of awareness, treatment and control in Mexico and among MAs. A national representative sample of the adult population from Mexico collected in 2000 (N=49 294), and data on 8688 MA participants in the 1999-2004 National Health and Nutrition Examination survey from the United States were available for analysis. US-born MAs and those born in Mexico were analysed separately in the US data. Lack of direct standardization of methods between surveys necessitated statistical adjustment of BP values. Analyses were based on persons aged 25-64 in each country. Sex- and age-adjusted mean systolic/diastolic BPs were 122/80, 119/71 and 120/73 in Mexicans, immigrant MAs and US-born MAs, respectively. The prevalences of hypertension (BP > or = 140/90 or treatment) were 33, 17 and 22%. Hypertension control rates were 3.7, 32.1 and 37.9%, in the same groups. Awareness and treatment rates were 25 and 13% in Mexico and 54 and 46% among MAs in the United States, respectively. Hypertension appears to be more common in Mexico than among Mexican immigrants to the United States. Despite relatively low access to health insurance in the United States, hypertension control increased over the course of this migration.

Hydroxyvitamin D assays: An historical perspective from DEQAS.

Recent years have seen a substantial increase in demand for 25-hydroxyvitamin D (25-OHD) assays. DEQAS (the Vitamin D External Quality Assessment Scheme) has been monitoring the performance of these assays since 1989. The first DEQAS distribution was in June 1989 and results were submitted by 13 laboratories in the UK, two of which used HPLC/UV; the rest used ligand binding assays with a tritium tracer. Inter-laboratory CVs (ALTM) ranged from 29.3% (42.7nmol/L) to 53.7% (20.0nmol/L). Currently the scheme has participants in 56 countries using 30 methods or variants of methods. In January 2017, 918 participants returned results and inter-laboratory CVs (ALTM) ranged from 10.3% (73.1nmol/L) to 15.3% (29.4nmol/L). Over the last 27 years, there have been a number of significant milestones in assay development. The first major advance was the development of an iodinated 25-OHD tracer by Hollis and Napoli in 1992, subsequently used in an RIA kit marketed by DiaSorin. This and other commercial radioimmunoassays that followed brought 25-OHD assays within reach of many more non-specialist routine laboratories. With the introduction of fully automated non-isotopic assays without solvent extraction, measurement of 25-OHD became available to any clinical chemistry laboratory with an appropriate analytical platform. However, as the limitations of these non-extraction assays became apparent more laboratories started using LC-MS/MS methodology. Meanwhile the variable accuracy of 25-OHD methods has been addressed by the Vitamin D Standardization Program (VDSP) which encourages manufacturers to produce methods traceable to the reference measurement procedures (RMPs) of NIST, University of Ghent and the Centers for Disease Control and Prevention (CDC). DEQAS changed to an accuracy-based scheme in 2013 and now assesses assay accuracy against the NIST RMP. This review will use DEQAS results and statistics to chart the historical development in 25-OHD assay technology and highlight some of the problems encountered in obtaining reliable results for this most challenging of analytes.

Activity, adiposity and weight change in Jamaican adults.

OBJECTIVE: Populations in developing countries are particularly vulnerable to the development of obesity in the period of rapid transition to a more modernized lifestyle. We sought to determine the relationship between activity energy expenditure (AEE), adiposity and weight change in an adult population undergoing rapid socio-economic transition. METHODS: Total daily energy expenditure (TDEE) was measured using the doubly labelled water method, resting energy expenditure (REE) using indirect calorimetry and AEE calculated as the difference between TDEE and REE, in adults from a working class community in Spanish Town, Jamaica. During six years of follow-up, weight was measured between one and four times. Mixed effects regression modelling was used to test for association between components of the energy budget and weight change. RESULTS: Men (n = 17) weighed more but women (n = 18), had significantly more body fat, 38.5% vs 24.5%, respectively (p < 0.01). Men had higher levels of EE, particularly AEE after adjustment for body weight, 66.3 versus 46.4 kJ/kg.d for men and women, respectively (p < 0.001). At baseline, adjusted AEE was inversely associated with body fat in men and women, r = -0.46 and r = -0.48, respectively (p < 0.05). Mean rate of weight change was + 1.1 and + 1.2 kg/year for men and women, respectively. No component of EE, ie TDEE, REE or AEE, significantly predicted weight change in this small sample. CONCLUSIONS: These results suggest an important role for AEE in maintaining low levels of adiposity. The lack of association between EE and weight change, however, suggests populations in transition are at risk of obesity from environmental factors (eg dietary) other than simply declining physical activity levels.

Vitamin D measurement standardization: The way out of the chaos.

Substantial variability is associated with laboratory measurement of serum total 25-hydroxyvitamin D [25(OH)D]. The resulting chaos impedes development of consensus 25(OH)D values to define stages of vitamin D status. As resolving this situation requires standardized measurement of 25(OH)D, the Vitamin D Standardization Program (VDSP) developed methodology to standardize 25(OH)D measurement to the gold standard reference measurement procedures of NIST, Ghent University and CDC. Importantly, VDSP developed protocols for standardizing 25(OH)D values from prior research based on availability of stored serum samples. The effect of such retrospective standardization on prevalence of "low" vitamin D status in national studies reported here for The Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and the German Health Interview and Examination Survey for Children and Adolescents (KIGGS, 2003-2006) was such that in NHANES III 25(OH)D values were lower than original values while higher in KIGGS. In NHANES III the percentage with values below 30, 50 and 75 nmol/L increased from 4% to 6%, 22% to 31% and 55% to 71%, respectively. Whereas in KIGGS after standardization the percentage below 30, 50, and 70 nmol/L decreased from 28% to 13%, 64% to 47% and 87% to 85% respectively. Moreover, in a hypothetical example, depending on whether the 25(OH)D assay was positively or negatively biased by 12%, the 25(OH)D concentration which maximally suppressed PTH could vary from 20 to 35ng/mL. These examples underscore the challenges (perhaps impossibility) of developing vitamin D guidelines using unstandardized 25(OH)D data. Retrospective 25(OH)D standardization can be applied to old studies where stored serum samples exist. As a way forward, we suggest an international effort to identify key prior studies with stored samples for re-analysis and standardization initially to define the 25(OH)D level associated with vitamin D deficiency (rickets/osteomalacia). Subsequent work could focus on defining inadequacy. Finally, examples reported here highlight the importance of suspending publication of meta-analyses based on unstandardized 25(OH)D results.

Quality assessment of vitamin D metabolite assays used by clinical and research laboratories.

The Vitamin D External Quality Assessment Scheme (DEQAS) was launched in 1989 and monitors the performance of 25-hydroxyvitamin D (25-OHD) and 1,25- dihydroxyvitamin D (1,25(OH)2D) assays. In April 2015 a pilot scheme for 24,25-dihydroxyvitamin D (24,25(OH)2D) was introduced. The 25-OHD scheme is accuracy - based with target values assigned by the NIST Reference Measurement Procedure (RMP) for 25-OHD2 and 25-OHD3. A similar method is used to assign values for 3-epi-25-OHD. Five samples of human serum are distributed quarterly to over 1000 participants in 58 countries (April 2016) and clinical laboratories are expected to submit results within approximately 5 weeks. Research laboratories with assays run less frequently are not given a deadline. Archived samples with NIST- assigned values are also available. Performance is assessed on the first four samples with the fifth reserved for investigations e.g. recovery experiments or to assess the influence of other serum constituents such as lipids. DEQAS provides rapid feedback, with an on-line preliminary report available immediately after a participant submits results and a comprehensive report soon after the results deadline. In 2015, DEQAS investigations revealed that several 25-OHD immunoassays under-recovered 25-OHD2 and 25-OHD results were falsely low on a sample with a modestly raised triglyceride concentration. An RMP for 1,25 (OH)2D is not yet available and results are judged against the Method Mean. Free advice is available from the DEQAS Advisory Panel which includes experts on methodology and biostatistics. DEQAS collaborates closely with the Vitamin D Standardization Program (VDSP) and both organizations have successfully worked with participants and manufacturers to improve the accuracy of vitamin D assays.

Developing vitamin D dietary guidelines and the lack of 25-hydroxyvitamin D assay standardization: The ever-present past.

Unstandardized laboratory measurement of 25-hydroxyvitamin D (25(OH)D) confounds efforts to develop clinical and public health vitamin D guidelines. The Vitamin D Standardization Program (VDSP), an international collaborative effort, was founded in 2010 to correct this problem. Nearly all published vitamin D research is based on unstandardized laboratory 25(OH)D measurements. While it is impossible to standardize all old data, it may be possible to identify a small subset of prior studies critical to guidelines development. Once identified it may be possible to calibrate their 25(OH)D values to the NIST and Ghent University reference measurement procedures using VDSP methods thereby permitting future guidelines to be based on standardized results. We simulated the calibration of a small set of ten clinical trials of vitamin D supplementation on achieved 25(OH)D under minimal sun exposure. These studies were selected because they played a prominent role in setting the 2010 vitamin D dietary reference intakes (DRI). Using random-effects meta-regression analysis, Vitamin D External Quality Assessment (DEQAS) data on assay bias was used to simulate the potential bias due to the lack of assay standardization by calibrating the achieved 25(OH)D levels from those 10 studies to: (1) the largest negative, and (2) the largest positive bias from the DEQAS all laboratory trimmed mean (ALTM) for the appropriate assay and year of analysis. For a usual vitamin D intake of 600IU/day the difference in mean achieved 25(OH)D values for those two options was 20nmol/L. However, without re-calibration of 25(OH)D values it is impossible to know the degree to which any of the current guidelines may have been biased. This approach may help stimulate the search for and standardization of that small subset of key studies and, in the cases where standardization is impossible, to identify areas of urgently needed vitamin D research.

Prediction of mortality risk by different methods of indexation for left ventricular mass.

OBJECTIVES: We sought to compare the predictive value of echocardiographically determined left ventricular hypertrophy on death from all causes and cardiac mortality using various methods of indexation for left ventricular mass. BACKGROUND: Considerable controversy exists regarding the optimal method for indexing left ventricular mass to body size in the clinical setting. METHODS: The study included 988 consecutive patients who had both coronary angiograms and echocardiographic examinations in an inner-city public hospital in Chicago, Illinois. Patients were followed up for a mean of 7 years (range 2 to 11). RESULTS: Various left ventricular mass indexes (e.g., mass indexed for height, height2, height2.13, height2.7, body surface area and body surface area1.5 were highly correlated (r = 0.90 to 0.99). Used as a continuous measure, an increase in any left ventricular mass index was associated with similar risk of death from all causes and cardiac diseases. Although left ventricular hypertrophy assessed by mass indexed for body surface area using the published conventional partition values provided somewhat better prediction, the adjusted relative risk was in general not significantly different from hypertrophy based on other indexes. Patients with left ventricular hypertrophy defined concordantly by indexes based on both body surface area and height (or height2.7) had, by definition, the highest average mass indexes among all groups and experienced as much as a threefold greater risk of death than those without hypertrophy. A small proportion of patients (12%) who were classified into the hypertrophy group by height-based indexes alone, but not by body surface area, had a moderate increase in mass and showed no increase in risk, even though being overweight was extremely prevalent in this group. CONCLUSIONS: Because of the high correlation among various body size indexes, left ventricular hypertrophy, defined by different indexes for left ventricular mass, similarly confers increased risk of mortality in patients with or without coronary artery disease.

Leveraging social influence to address overweight and obesity using agent-based models: the role of adolescent social networks.

The prevalence of adolescent overweight and obesity (hereafter, simply "overweight") in the US has increased over the past several decades. Individually-targeted prevention and treatment strategies targeting individuals have been disappointing, leading some to propose leveraging social networks to improve interventions. We hypothesized that social network dynamics (social marginalization; homophily on body mass index, BMI) and the strength of peer influence would increase or decrease the proportion of network member (agents) becoming overweight over a simulated year, and that peer influence would operate differently in social networks with greater overweight. We built an agent-based model (ABM) using results from R-SIENA. ABMs allow for the exploration of potential interventions using simulated agents. Initial model specifications were drawn from Wave 1 of the National Longitudinal Study of Adolescent Health (Add Health). We focused on a single saturation school with complete network and BMI data over two waves (n = 624). The model was validated against empirical observations at Wave 2. We focused on overall overweight prevalence after a simulated year. Five experiments were conducted: (1) changing attractiveness of high-BMI agents; (2) changing homophily on BMI; (3) changing the strength of peer influence; (4) shifting the overall BMI distribution; and (5) targeting dietary interventions to highly connected individuals. Increasing peer influence showed a dramatic decrease in the prevalence of overweight; making peer influence negative (i.e., doing the opposite of friends) increased overweight. However, the effect of peer influence varied based on the underlying distribution of BMI; when BMI was increased overall, stronger peer influence increased proportion of overweight. Other interventions, including targeted dieting, had little impact. Peer influence may be a viable target in overweight interventions, but the distribution of body size in the population needs to be taken into account. In low-obesity populations, strengthening peer influence may be a useful strategy.

Assessing the effect of fatty acids on prostate carcinogenesis in humans: does self-reported dietary intake rank prostatic exposure correctly?

BACKGROUND: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown. OBJECTIVE: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue. DESIGN: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients. RESULTS: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes. CONCLUSION: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

Patterns of comorbidity and mortality risk in blacks and whites.

Comorbidity, the co-existence of multiple chronic conditions in a single individual, has been shown to modify the prognosis of disease states. To estimate disease burdens within and among racial subpopulations of the United States, we examined cross-sectional patterns of comorbidity and their impact on survival using data from the NHANES-1 Epidemiologic Follow-up Study (NHEFS). We considered the occurrence of four cardiovascular conditions: stroke, coronary heart disease, hypertension and diabetes. We summarize the joint occurrence of these four conditions using these different methodologies: the number of conditions occurring in each individual and two summaries that weight the conditions according to their prognostic significance. Using all three methodologies, we found an excess burden of chronic disease in black women as compared with white women. Black men had an excess burden compared to white men for the first two methodologies. However, when we model the relationship of the joint occurrence of the conditions to subsequent mortality, black men and white men are seen to have a similar burden. This similarity of black and white men is due to an interaction between race and prevalent stroke in men that we hypothesize may be due to the small number of black men available for study. Given the apparent conditioning effect of co-existing diseases, it is evident that estimation of disease burdens among groups that differ in terms of health status, in particular among U.S. blacks and whites, requires accounting for the occurrence of multiple chronic diseases. Using either the number of conditions or the prognosis weighted summary, we demonstrated a higher burden of the conditions considered in blacks that in whites in a sample of the U.S. population.

Height and risk of fatal prostate cancer: findings from the National Health Interview Survey (1986 to 1994).

PURPOSE: Height is determined by genetic and nutritional factors mediated through the endocrine system early in life and, thus, may be related to subsequent risk of fatal prostate cancer. This hypothesis was examined in a large representative U.S. national sample. METHODS: Data from the National Health Interview Survey (NHIS) were analyzed to determine whether height was prospectively related to the risk of fatal prostate cancer in 110,042 men age > or = 50 years old interviewed between 1986 and 1994. Height was self-reported and vital status and causes of death ascertained using the National Death Index. Endpoints were deaths that listed prostate cancer as the underlying cause and deaths with any mention of prostate cancer. Relative risks (RR) and their 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, race, weight, and education. RESULTS: Six hundred and thirty-three deaths listing of prostate cancer as the underlying cause and 910 deaths with any mention of prostate cancer were identified. Height was associated neither with risk of death with prostate cancer listed as the underlying cause nor with risk of death with any mention of prostate cancer (multivariate p for trend = 0.1318 and 0.0698, respectively). Risks were marginally greater among the tallest men compared to the shortest (< or = 171.4 vs. > or = 182.9 cm), but not significantly (RR = 1.21, 95% CI = 0.92 to 1.57, and RR = 1.24, 95% CI = 0.98 to 1.58 for 'underlying cause' and 'any mention', respectively). CONCLUSIONS: Height alone was not related to risk of fatal prostate cancer in this population.

Relative weight and mortality in U.S. blacks and whites: findings from representative national population samples.

PURPOSE: To examine the impact of relative weight on mortality in black and white men and women. METHODS: Two representative national populations samples were used: the NHANES-I Epidemiologic Follow-up Study (NHEFS), and the National Health Interview Survey (NHIS). The principal analysis focused on 13,242 participants in the NHEFS and 114,954 in the NHIS. Minimum mortality was estimated from both categorical analysis and a logistic model. RESULTS: Minimum mortality ranged from a body mass index (BMI) of 25 to 32 kg/m2. The model-estimated BMI of minimum mortality for NHEFS was 27.1 (24.8-29.4, 95% CI), 26.8 (24.7-28.9, 95% CI), 24.8 (23.8-25.9, 95% CI) and 24.3 (23.2-25.4, 95% CI); for black men, black women, white men and white women, respectively, whereas for NHIS the corresponding values were 30.2 (24.8-35.6, 95% CI) 26.4 (24.2-28.7, 95% CI), 27.1 (25.5-28.7, 95% CI), and 25.6 (24.2-27.0, 95% CI). In all groups the shape of the relative risk curve was virtually identical and a broad range of BMI values in the middle of the distribution was associated with low relative mortality risk. Averaging the results from both surveys, the observed BMI of minimum risk was 3.1 kg/m2 higher in black men and 1.5 kg/m2 higher in black women than in their white counterparts; when adjusted for covariates these differences were only of borderline statistical significance, however. CONCLUSIONS: Because of the wide range of BMI values associated with low risk, and the consistency of the point of the up-turn in risk, group specific definitions of optimal values do not appear to be warranted.

The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited.

PURPOSE: To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. METHODS: The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). RESULTS: We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. CONCLUSIONS: Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up.