Quantitative Bias Analysis of misclassification in case-control studies: an example with Human Papillomavirus and Oropharyngeal Cancer.

OBJECTIVE: Laprise et al. (2019) observed a positive association between oral sex practices and oropharyngeal cancers (OPC) among HPV-negative individuals. Because oral HPV infections are likely to be transmitted through oral sex, these results are counterintuitive. We revisit Laprise et. al's analysis with the objective of estimating the impact of misclassification of HPV infection on the association between oral sex practices and OPC. METHODS: Data were drawn from the Head and Neck Cancer (HeNCe) Life study, a hospital-based case control study of head and neck cancer with frequency-matched controls by age and sex from 4 major referral hospitals in Montreal, Canada. We included only OPC cases (n = 188) and controls (n = 429) and used predictive value weighting, under differential and non-differential scenarios, to evaluate the misclassification. Subsequently, we used logistic regression and 95% confidence intervals to estimate the association between oral sex practice and OPC among HPV-negative individuals. RESULTS: Our results showed that the previously reported association between oral sex practices and OPC among HPV-negative individuals was attenuated or nullified both under differential and non-differential scenarios. CONCLUSION: The association between oral sex practice and OPC could be explained by biases in the data (e.g., HPV mediator misclassification). Our results highlight the need for widespread adoption of Quantitative Bias Analysis in oral health research.

Cost-effectiveness of active case-finding of household contacts of pulmonary tuberculosis patients in a low HIV, tuberculosis-endemic urban area of Lima, Peru.

We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

Cervical dilation at time of caesarean delivery in nulliparous women: a population-based cohort study.

OBJECTIVES: Our objective was to describe contemporary practice patterns in the timing of caesarean delivery in relation to cervical dilation, overall and by indication for caesarean. Our secondary objective was to examine how commonly caesarean delivery was performed for labour dystocia at dilations below 4 cm or without the use of oxytocin, overall and between hospitals. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Alberta, and British Columbia, Canada, 2008-2012. POPULATION: Nulliparous women in labour who delivered term singletons in cephalic position. METHODS: Histograms were used to examine the distribution of cervical dilation at time of caesarean delivery, overall and by indication for caesarean. Funnel plots were used to illustrate variation in hospital-level rates of caesarean deliveries for labour dystocia that were performed early (<4 cm dilation) or without the use of oxytocin. MAIN OUTCOME MEASURES: Cervical dilation (in centimetres) at time of caesarean delivery. RESULTS: The population-based cohort comprised 392 025 women, of whom 18.8% had a caesarean delivery. Of first-stage caesareans for labour dystocia in women who entered labour spontaneously, 13.6% (95% CI 12.9, 14.2) had dilations <4 cm [hospital-level inter-quartile range (IQR): 6.2% to 20.0%] and 29.5% (95% CI 28.6, 30.4) did not receive oxytocin to treat their dystocia (hospital-level IQR: 22.1-54.6%). CONCLUSIONS: The proportion of caesareans done before 4 cm dilation or without oxytocin varies substantially across hospitals and suggests the need for institutions to review their practices and ensure that management of labour practice guidelines are followed. TWEETABLE ABSTRACT: Many caesareans for labour dystocia are performed early during labour (<4 cm dilation) or without oxytocin.

Inequalities in Indigenous Oral Health: Findings from Australia, New Zealand, and Canada

The objective was to compare absolute differences in the prevalence of Indigenous-related inequalities in dental disease experience and self-rated oral health in Australia, Canada, and New Zealand. Data were sourced from national oral health surveys in Australia (2004 to 2006), Canada (2007 to 2009), and New Zealand (2009). Participants were aged ≥18 y. The authors measured age- and sex-adjusted inequalities by estimating absolute prevalence differences and their corresponding 95% confidence intervals (95% CIs). Clinical measures included the prevalence of untreated decayed teeth, missing teeth, and filled teeth; self-reported measures included the prevalence of "fair" or "poor" self-rated oral health. The overall pattern of Indigenous disadvantage was similar across all countries. The summary estimates for the adjusted prevalence differences were as follows: 16.5 (95% CI: 11.1 to 21.9) for decayed teeth (all countries combined), 18.2 (95% CI: 12.5 to 24.0) for missing teeth, 0.8 (95% CI: -1.9 to 3.5) for filled teeth, and 17.5 (95% CI: 11.3 to 23.6) for fair/poor self-rated oral health. The I2 estimates were small for each outcome: 0.0% for decayed, missing, and filled teeth and 11.6% for fair/poor self-rated oral health. Irrespective of country, when compared with their non-Indigenous counterparts, Indigenous persons had more untreated dental caries and missing teeth, fewer teeth that had been restored (with the exception of Canada), and a higher proportion reporting fair/poor self-rated oral health. There were no discernible differences among the 3 countries.

Fetal death and preterm birth associated with maternal influenza vaccination: systematic review.

BACKGROUND: Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. OBJECTIVES: To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. SEARCH STRATEGY: We searched bibliographic databases from inception to April 2014. SELECTION CRITERIA: Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data from studies meeting the inclusion criteria. MAIN RESULTS: We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity (I(2) = 57%). AUTHORS' CONCLUSIONS: Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.

Place and health in diabetes: the neighbourhood environment and risk of depression in adults with type 2 diabetes.

BACKGROUND: Depression is a common co-illness in people with diabetes. Evidence suggests that the neighbourhood environment impacts the risk of depression, but few studies have investigated this effect in those with diabetes. We examined the effect of a range of neighbourhood characteristics on depression in people with Type 2 diabetes. METHODS: This cohort study used five waves of data from 1298 participants with Type 2 diabetes from the Diabetes Health Study (2008-2013). We assessed depression using the Patient Health Questionnaire. We measured neighbourhood deprivation using census data; density of services using geospatial data; level of greenness using satellite imagery; and perceived neighbourhood characteristics using survey data. The effect of neighbourhood factors on risk of depression was estimated using survival analysis, adjusting for sociodemographic variables. We tested effect modification by age, sex and socio-economic characteristics using interaction terms. RESULTS: More physical activity facilities, cultural services and a greater level of greenness in the neighbourhood were associated with a lower risk of depression in our sample, even after adjusting for confounders. Material deprivation was associated with increased risk of depression, particularly in participants who were older or retired. CONCLUSIONS: Characteristics of neighbourhoods were associated with the risk of depression in people with Type 2 diabetes and there were vulnerable subgroups within this association. Clinicians are encouraged to consider the neighbourhood environment of their patients when assessing the risk of depression. Future intervention research is need for health policy recommendations.

Geographic predictors of primary multidrug-resistant tuberculosis cases in an endemic area of Lima, Peru.

SETTING: Peru reports among the highest multidrug-resistant tuberculosis (MDR-TB) rates in the Americas, with a growing proportion in previously untreated tuberculosis (TB) cases. The identification of clusters of primary MDR-TB compared with drug-susceptible TB (DS-TB) could help prioritize interventions. OBJECTIVE: To examine the clustering of primary MDR-TB case residences and their proximity to high-risk locations in San Juan de Lurigancho District, Lima, Peru. DESIGN: Enrolled primary MDR-TB and primary DS-TB cases were interviewed and their primary residence was recorded using handheld Global Positioning System devices. Kuldorff's spatial scan statistic was used for cluster detection (SaTScan(TM), v. 9.1.1). Identified clusters were visualized in Quantum Geographic Information Systems software (v1.8.0). The following cluster centers were tested: a health centre with the highest TB and MDR-TB rates (Clinic X), a hospital and two prisons. Using regression analyses, we examined predictors of primary MDR-TB cases. RESULTS: A statistically significant cluster of primary MDR-TB cases was identified within a 2.29 km radius around Clinic X. Proximity to Clinic X remained a significant predictor of primary MDR-TB in adjusted regression analyses. CONCLUSION: We identified a hotspot of primary MDR-TB cases around Clinic X in a TB-endemic area. Causes of this clustering require investigation; targeted interventions for this high-risk area should be considered.

Thyroid hormones are associated with cognitive function: moderation by sex, race, and depressive symptoms.

CONTEXT: Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. OBJECTIVE: We investigated associations between thyroid hormones and cognitive performance, while testing effect modification by sex, race, and elevated depressive symptoms (EDS). DESIGN: This cross-sectional study used extensive data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. SETTING: The study was conducted in Baltimore, Maryland, from 2004 to 2009. PARTICIPANTS: PARTICIPANTS were U.S. adults aged 30 to 64 years. The sample size ranged from 1275 to 1346. MAIN OUTCOME MEASURES: Outcomes included 13 cognitive test scores spanning domains of learning/memory, language/verbal, attention, visuo-spatial/visuo-construction, psychomotor speed, executive function, and mental status. RESULTS: Within reference ranges and after Bonferroni correction, elevated free thyroxine (fT4) was associated with better performance on tests of visuo-spatial/visuo-construction ability (overall, women, and African Americans) and learning/memory (women and African Americans), whereas a higher total thyroxine (tT4) level was associated with better performance in the domain of psychomotor speed (individuals without EDS) and higher levels of both fT4 and tT4 were linked to better language/verbal test performance among men. In contrast, higher T3(% uptake) was related to better performance on tests of visuo-spatial/visuo-construction ability and psychomotor speed among whites. When the above reference range was compared within the overall population and after Bonferroni correction, a within reference range fT4 was linked to better performance on visuo-spatial/visuo-constrution ability and psychomotor speed, whereas a below normal range TSH level (compared with the reference range) was linked to better performance in domains of psychomotor speed and attention. CONCLUSIONS: Thyroid hormones and cognition are closely linked differentially by sex, race, and EDS status.

Socio-economic inequalities and oral health in Canada and the United States.

This paper describes and compares the magnitude of socio-economic inequalities in oral health among adults in Canada and the US over the past 35 years. We analyzed data from nationally representative examination surveys in Canada and the US: Nutrition Canada National Survey (1970-1972, N = 11,546), Canadian Health Measures Survey (2007-2009, N = 3,508), The First National Health and Nutrition Examination Survey (1971-1974, N = 13,131), and National Health and Nutrition Examination Survey (2007-2008, N = 5,707). Oral health outcomes examined were prevalence of edentulism, proportion of individuals having at least 1 untreated decayed tooth, and proportion of individuals having at least 1 filled tooth. Sociodemographic indicators included in our analysis were place of birth, education, and income. Data were age-adjusted, and survey weights were used to account for the complex survey design in making population inferences. Our findings demonstrate that oral health outcomes have improved for adults in both countries. In the 1970s, Canada had a higher prevalence of edentulism and dental decay and lower prevalence of filled teeth. This was also combined with a more pronounced social inequality gradient among place of birth, education, and income groups. Over time, both countries demonstrated a decline in absolute socio-economic inequalities in oral health.

Prevalence of obesity and overweight in urban adult Nigerians.

Obesity is increasingly a major health problem in parts of the developing world. It has reached epidemic proportions among Africans living in the Western Hemisphere; similar potential may exist in urban Africa. We explored this possibility in an urban setting in Nigeria, Africa's most populous nation. A screening survey was carried out among randomly selected 998 civil servants, 581 men and 417 women, in Ibadan, a major Nigerian city. Biographical data were collected using standardized questionnaires, and measurements of anthropometric indices, blood pressures and plasma glucose concentration. Obesity and overweight were defined by body mass index based on international criteria. Prevalence of obesity was 8.82% (confidence interval [CI]=7.13%, 10.75%), overweight 17.45% (CI=15.12%, 19.95%), and overweight plus obesity=26.18% (CI=23.47%, 29.03%). Prevalence of obesity among the women was 17.27% (CI=13.76%, 21.24%) and for men 2.75% (CI=1.58%, 4.43%). Among the women 42% were obese or overweight compared with 15% of the male population. Obesity and overweight were associated with higher socioeconomic status. Prevalence of obesity and overweight in the study population is comparable to rates seen in many industrialized countries, and rapidly emerging urbanized populations in Africa.

Do the wealthy have a health advantage? Cardiovascular disease risk factors and wealth.

The use of wealth as a measure of socioeconomic status (SES) remains uncommon in epidemiological studies. When used, wealth is often measured crudely and at a single point in time. Our study explores the relationship between wealth and three cardiovascular disease (CVD) risk factors (smoking, obesity and hypertension) in a US population. We improve upon existing literature by using a detailed and validated measure of wealth in a longitudinal setting. We used four waves of data from the Panel Study of Income Dynamics (PSID) collected between 1999 and 2005. Inverse probability weights were employed to control for time-varying confounding and to estimate both relative (risk ratio) and absolute (risk difference) measures of effect. Wealth was defined as inflation-adjusted net worth and specified as a six category variable: one category for those with less than or equal to zero wealth and quintiles of positive wealth. After adjusting for income and other time-varying confounders, as well as baseline covariates, the risk of becoming obese was inversely related to wealth. There was a 40%-89% higher risk of becoming obese among the less wealthy relative to the wealthiest quintile and 11 to 25 excess cases (per 1000 persons) among the less wealthy groups over six years of follow up. Smoking initiation had similar but more moderate effects; risk ratios and differences both revealed a smaller magnitude of effect compared to obesity. Of the three CVD risk factors examined here, hypertension incidence had the weakest association with wealth, showing a smaller increased risk and fewer excess cases among the less wealthy groups. In conclusion, this study found a strong inverse association between wealth and obesity incidence, a moderate inverse association between wealth and smoking initiation and a weak inverse association between wealth and hypertension incidence after controlling for income and other time-varying confounders.

Neighborhood deprivation and adverse birth outcomes among diverse ethnic groups.

PURPOSE: Living in a socioeconomically deprived neighborhood has been associated with an increased risk of adverse birth outcomes. However, variation in the effect of neighborhood deprivation among diverse ethnic groups has not been studied. METHODS: Using linked hospital discharge and birth data for 517,994 singleton live births in New York City from 1998 through 2002, we examined the association between neighborhood deprivation, preterm birth (PTB), and term low birthweight (TLBW) (>or=37 weeks and <2500g). Adjusted odds ratios (aORs) for PTB (<32 and 33-36 weeks) and TLBW were estimated using logistic regression. RESULTS: The aOR for PTB of less than 32 weeks for the highest quartile of deprivation compared to the lowest was 1.24 (95% confidence limit [CL] = 1.13, 1.36), for PTB 33-36 weeks was 1.06 (95% CL = 1.01, 1.11), and for TLBW was 1.19 (95% CL = 1.11, 1.27). Measures of association varied by ethnicity; aORs of the greatest magnitude for PTB were found among Hispanic Caribbean women (PTB < 32 weeks: aOR = 1.63, 95% CL = 1.27, 2.10; PTB 33-36 weeks: aOR = 1.32, 95% CL = 1.02, 1.70), and for TLBW among African women (aOR = 1.47, 95% CL = 1.02, 2.13). CONCLUSIONS: The mechanisms linking neighborhood deprivation to adverse birth outcomes may differ depending on individual ethnicity and/or cultural context and should be investigated in future research.

Obesity, race/ethnicity and life course socioeconomic status across the transition from adolescence to adulthood.

BACKGROUND: Differences in the association of socioeconomic status (SES) with obesity may underlie the racial/ethnic disparities in obesity that increase dramatically across the transition to adulthood in the United States. The aim of this study was to examine racial/ethnic differences in the influence of life course SES on longitudinal obesity patterns from adolescence to adulthood. METHODS: Latent class analysis was used on a nationally representative, diverse sample of 12 940 adolescents followed into young adulthood (mean age = 21.7 years) to identify life course SES group profiles based on SES data in adolescence and young adulthood. Gender-stratified multinomial logistic regression models estimated the association of SES groups with obesity incidence and persistence versus staying non-obese. RESULTS: No significant interactions with race/ethnicity were observed, although racial/ethnic minorities had the highest obesity risk across SES groups. Racial/ethnic-pooled associations between disadvantaged SES exposure and higher obesity risk were strong but differed by gender. Males with a disadvantaged background who experienced early transitions into the labour force, marriage and residential independence had the highest risk of obesity incidence (relative risk ratio (RRR) = 1.64; 95% confidence interval (CI) 1.12 to 2.40), while females exposed to persistent adversity were at highest risk (RRR = 3.01, 95% CI 1.95 to 4.66). In general, SES group membership had a stronger relationship with obesity persistence than incidence. CONCLUSIONS: The relationship between SES and obesity patterns is similar across race/ethnicity and differs by gender during the transition to adulthood. However, stronger associations with obesity persistence and enduring racial/ethnic disparities in obesity risk across SES groups suggest that these social factors play a larger role in disparities earlier in the life course.

Ethnicity and gestational diabetes in New York City, 1995-2003.

OBJECTIVE: To characterise the patterns of occurrence of gestational diabetes among a wide range of ethnic groups that reside in New York City. DESIGN: Birth records and hospital discharge data were linked to more accurately assess the risk of gestational diabetes by ethnicity, compare risk in US-born to foreign-born women, and assess time trends. SETTING: New York City. POPULATION: All singleton live births occurring between 1995 and 2003. METHODS: Multivariable binomial regression analysis of ethnicity and gestational diabetes, yielding adjusted risk ratios with non-Hispanic white women as the referent. MAIN OUTCOME MEASURE: Diagnosis of gestational diabetes on birth certificate or in hospital discharge. RESULTS: Adjusted relative risks (aRRs) were modestly elevated for African-Americans and sub-Saharan Africans and somewhat higher (<2.0) for non-Hispanic Caribbeans, Hispanic Caribbeans, Central Americans, and South Americans. The aRR was 4.7 (95% CI = 4.6-4.9) for South Central Asians (with an absolute gestational diabetes risk of 14.3%), 2.8 (95% CI = 2.7-3.0) among South-East Asian and Pacific Islanders, and 2.3 (95% CI = 2.2-2.4) among East Asians. Among South Central Asians, the greatest risks were found for women from Bangladesh (aRR = 7.1, 95% CI = 6.8-7.3). Foreign-born women consistently had higher risk than US-born women. Risk for gestational diabetes increased over time among South Central Asians, some Hispanic groups, and African-Americans. CONCLUSIONS: Risk of gestational diabetes appears to vary markedly among ethnic groups, subject to potential artefacts associated with screening and diagnosis. These differences would have direct implications for health care and may suggest aetiologic hypotheses.

Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood.

OBJECTIVE: To examine the association between cumulative life course and adult socioeconomic status (SES) and adult levels of inflammatory risk markers (fibrinogen, white blood cell count (WBC), C-reactive protein (CRP), von Willebrand factor (vWF) and an overall inflammatory score). DESIGN: Retrospective cohort study. SETTING: 12,681 white and African-American participants in the Atherosclerosis Risk in Communities (ARIC) study and two ancillary studies. METHODS: Participants provided information on SES and place of residence in childhood and young (30-40 years) and mature (45+) adulthood. Residences were linked to census data for neighbourhood SES information. Multiple imputation (MI) was used for missing data. Linear regression and adjusted geometric means were used to estimate the effects of SES on inflammatory risk marker levels. RESULTS: Graded, statistically significant associations were observed between greater cumulative life-course exposure to low education and social class and elevated levels of fibrinogen and WBC among white participants. Stronger graded, statistically significant associations were observed between low adult education, social class and neighbourhood SES and elevated inflammatory levels. Associations were weaker and less consistent in African-Americans. Covariate adjustment attenuated results but many associations remained strong. CONCLUSIONS: Our results suggest that cumulative exposure to adverse SES conditions across the life course and low adult SES are associated with an elevated systemic inflammatory burden in adulthood. Chronic systemic inflammation may be one pathway linking low life-course SES and elevated cardiovascular disease risk.

When to refer patients with chronic kidney disease for vascular access surgery: should age be a consideration?

To determine whether age should inform our approach toward permanent vascular access placement in patients with chronic kidney disease, we conducted a retrospective cohort study among 11 290 non-dialysis patients with an estimated glomerular filtration rate (eGFR) <25 ml/min/1.73 m(2) based on 2000-2001 outpatient creatinine measurements in the Department of Veterans Affairs. For each age group, we examined the percentage of patients that had and had not received a permanent access by 1 year after cohort entry, and the percentage in each of these groups that died, started dialysis, or survived without dialysis. We also modeled the number of unnecessary procedures that would have occurred in theoretical scenarios based on existing vascular access guidelines. The mean eGFR was 17.7 ml/min/1.73 m(2) at cohort entry. Twenty-five percent (n=2870) of patients initiated dialysis within a year of cohort entry. Among these, only 39% (n=1104) had undergone surgery to place a permanent access beforehand. As compared with younger patients, older patients were less likely to undergo permanent access surgery, but also less likely to start dialysis. In all theoretical scenarios examined, older patients would have been more likely than younger patients to receive unnecessary procedures. If all patients had been referred for permanent access surgery at cohort entry, the ratio of unnecessary to necessary procedures after 2 years of follow-up would have been 5:1 for patients aged 85-100 years but only 0.5:1 for those aged 18-44 years. Currently recommended approaches to permanent access placement based on a single threshold level of renal function for patients of all ages are not appropriate.

Proteinuria in obstructive sleep apnea.

BACKGROUND: Previous studies have reported an association between obstructive sleep apnea (OSA) and proteinuria, but are limited in their ability to assess proteinuria accurately, to adjust for confounders such as obesity, or to exclude confidently underlying renal disease in patients with OSA and nephrotic-range proteinuria. METHODS: The spot urine protein/creatinine ratio was measured in a prospective consecutive series of 148 patients referred for polysomnography who were not diabetic and had not been treated previously for OSA. The urine protein/creatinine ratio was compared across four levels of OSA severity, based on the frequency of apneas and hypopneas per hour: <5 (absent), 5 to 14.9 (mild), 15 to 29.9 (moderate), and > or =30 (severe). RESULTS: The median level of urine protein/creatinine ratio in all categories of OSA was <0.2 (range 0.03 to 0.69; median 0.06 in patients with normal apnea hypopnea index, 0.06, 0.07, 0.07 in patients with mild, moderate, and severe OSA, respectively). Eight subjects had a urine protein/creatinine ratio greater than 0.2. Univariate analysis showed a significant association between urine protein/creatinine ratio and older age (P < 0.0001), hypertension (P < 0.0001), coronary artery disease (P = 0.003), and arousal index (P = 0.003). Body mass index (P = 0.16), estimated creatinine clearance (P = 0.17), and apnea hypopnea index (P = 0.13) were not associated with the urine protein/creatinine ratio. In multiple regression analysis, only age and hypertension were independent positive predictors of the urine protein/creatinine ratio (P < 0.0001, R2 = 0.17). CONCLUSION: Clinically significant proteinuria is uncommon in sleep apnea. Nephrotic range proteinuria should not be ascribed to sleep apnea and deserves a thorough renal evaluation.

Commentary: considerations for use of racial/ethnic classification in etiologic research.

Numerous authors have critiqued the use of race as an etiologic quantity in medical research. Despite this criticism, the use of variables encoding racial/ethnic categorization has increased in epidemiology, and most researchers agree that important variation in disease risk is captured by this classification system. Previous discussions have generally neglected to articulate guidelines for appropriate use of racial/ethnic information in etiologic research. The authors summarize the logical, conceptual, and practical problems associated with the "ethnic paradigm" as currently applied in biomedical sciences and offer a set of methodological recommendations toward more valid use of racial/ethnic classification in etiologic studies. These suggested guidelines address issues of variable definition, study design, and covariate control, providing a consistent foundation for etiologic research programs that neither ignore racial/ethnic disease disparities nor obfuscate the nature of these disparities through inappropriate analytical approaches. This methodological analysis of racial/ethnic classification as an epidemiologic quantity provides a formal basis for a focus on racism (i.e., social relations) rather than race (i.e., innate biologic predisposition) in the interpretation of racial/ethnic "effects."

Diagnostic value of iron indices in hemodialysis patients receiving epoetin.

BACKGROUND: Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However, considerable controversy exists regarding the best strategies for diagnosis and treatment. METHODS: As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin, we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation, and serum ferritin. If a patient had serum ferritin <100 ng/mL or the combination of serum ferritin <400 ng/mL and a transferrin saturation <20%, he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial, the effect of its administration on iron indices and epoetin dose, and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. RESULTS: Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin <200 ng/mL had the best positive predictive value (76%) for predicting a response to parenteral iron administration, but it still had limited clinical utility. CONCLUSIONS: Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility.