The impact of prenatal dog keeping on infant gut microbiota development.

INTRODUCTION: Prenatal and early-life dog exposure has been linked to reduced childhood allergy and asthma. A potential mechanism includes altered early immune development in response to changes in the gut microbiome among dog-exposed infants. We thus sought to determine whether infants born into homes with indoor dog(s) exhibit altered gut microbiome development. METHODS: Pregnant women living in homes with dogs or in pet-free homes were recruited in southeast Michigan. Infant stool samples were collected at intervals between 1 week and 18 months after birth and microbiome was assessed using 16S ribosomal sequencing. Perinatal maternal vaginal/rectal swabs and stool samples were sequenced from a limited number of mothers. Mixed effect adjusted models were used to assess stool microbial community trajectories comparing infants from dog-keeping versus pet-free homes with adjustment for relevant covariates. RESULTS: Infant gut microbial composition among vaginally born babies became less similar to the maternal vaginal/rectal microbiota and more similar to the maternal gut microbiota with age-related accumulation of bacterial species with advancing age. Stool samples from dog-exposed infants were microbially more diverse (p = .041) through age 18 months with enhanced diversity most apparent between 3 and 6 months of age. Statistically significant effects of dog exposure on ß-diversity metrics were restricted to formula-fed children. Across the sample collection period, dog exposure was associated with Fusobacterium genera enrichment, as well as enrichment of Collinsella, Ruminococcus, Clostridaceae and Lachnospiraceae OTUs. CONCLUSION: Prenatal/early-life dog exposure is associated with an altered gut microbiome during infancy and supports a potential mechanism explaining lessened atopy and asthma risk. Further research directly linking specific dog-attributable changes in the infant gut microbiome to the risk of allergic disorders is needed.

Pediatric asthma incidence rates in the United States from 1980 to 2017.

BACKGROUND: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. OBJECTIVE: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. METHODS: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. RESULTS: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. CONCLUSIONS: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.

Increased risk of asthma at age 10 years for children sensitized to multiple allergens.

BACKGROUND: Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts. OBJECTIVE: To determine whether these risks persist into later childhood. METHODS: In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed. RESULTS: Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P < .001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P < .001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P < .001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified. CONCLUSION: The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

Infant Feeding Practices and Subsequent Dietary Patterns of School-Aged Children in a US Birth Cohort.

BACKGROUND: Infant feeding practices are thought to shape food acceptance and preferences. However, few studies have evaluated whether these affect child diet later in life. OBJECTIVE: The study objective was to examine the association between infant feeding practices and dietary patterns (DPs) in school-aged children. DESIGN: A secondary analysis of data from a diverse prospective birth cohort with 10 years of follow-up (WHEALS [Wayne County Health Environment Allergy and Asthma Longitudinal Study]) was conducted. PARTICIPANTS/SETTING: Children from the WHEALS (Detroit, MI, born 2003 through 2007) who completed a food screener at age 10 years were included (471 of 1,258 original participants). MAIN OUTCOME MEASURES: The main outcome was DPs at age 10 years, identified using the Block Kids Food Screener. STATISTICAL ANALYSIS PERFORMED: Latent class analysis was applied for DP identification. Breastfeeding and age at solid food introduction were associated with DPs using a 3-step approach for latent class modeling based on multinomial logistic regression models. RESULTS: The following childhood DPs were identified: processed/energy-dense food (35%), variety plus high intake (41%), and healthy (24%). After weighting for loss to follow-up and covariate adjustment, compared with formula-fed children at 1 month, breastfed children had 0.41 times lower odds of the processed/energy-dense food DP vs the healthy DP (95% CI 0.14 to 1.25) and 0.53 times lower odds of the variety plus high intake DP (95% CI 0.17 to 1.61), neither of which were statistically significant. Results were similar, but more imprecise, for breastfeeding at 6 months. In addition, the association between age at solid food introduction and DP was nonsignificant, with each 1-month increase in age at solid food introduction associated with 0.81 times lower odds of the processed/energy-dense food DP relative to the healthy DP (95% CI 0.64 to 1.02). CONCLUSIONS: A significant association between early life feeding practices and dietary patterns at school age was not detected. Large studies with follow-up beyond early childhood that can also adjust for the multitude of potential confounders associated with breastfeeding are needed.

Association between cesarean delivery types and obesity in preadolescence.

BACKGROUND/OBJECTIVES: The association between mode of delivery and childhood obesity remains inconclusive. Because few studies have separated C-section types (planned or unplanned C-section), our objective was to assess how these subtypes relate to preadolescent obesity. SUBJECTS/METHODS: The study consisted of 570 maternal-child pairs drawn from the WHEALS birth cohort based in Detroit, Michigan. Children were followed-up at 10 years of age where a variety of anthropometric measurements were collected. Obesity was defined based on BMI percentile (≥95th percentile), as well as through Gaussian finite mixture modeling on the anthropometric measurements. Risk ratios (RRs) and 95% confidence intervals (CIs) for obesity comparing planned and unplanned C-sections to vaginal deliveries were computed, which utilized inverse probability weights to account for loss to follow-up and multiple imputation for covariate missingness. Mediation models were fit to examine the mediation role of breastfeeding. RESULTS: After adjusting for marital status, maternal race, prenatal tobacco smoke exposure, maternal age, maternal BMI, any hypertensive disorders during pregnancy, gestational diabetes, prenatal antibiotic use, child sex, parity, and birthweight z-score, children born via planned C-section had 1.77 times higher risk of obesity (≥95th percentile), relative to those delivered vaginally ((95% CI) = (1.16, 2.72); p = 0.009). No association was found comparing unplanned C-section to vaginal delivery (RR (95% CI) = 0.75 (0.45, 1.23); p = 0.25). The results were similar but slightly stronger when obesity was defined by anthropometric class (RR (95% CI) = 2.78 (1.47, 5.26); p = 0.002). Breastfeeding did not mediate the association between mode of delivery and obesity. CONCLUSIONS: These findings indicate that children delivered via planned C-section-but not unplanned C-section-have a higher risk of preadolescent obesity, suggesting that partial labor or membrane rupture (typically experienced during unplanned C-section delivery) may offer protection. Additional research is needed to understand the biological mechanisms behind this effect, including whether microbiological differences fully or partially account for the association.

Breast Milk Transforming Growth Factor ß Is Associated With Neonatal Gut Microbial Composition.

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity.

The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease.

Usefulness of a home affluence scale administered to urban adolescents with asthma to estimate the family's socioeconomic status.

PURPOSE: Measurement of socioeconomic status (SES) is traditionally based on education, income, and occupation. This information may not be readily available from adolescents participating in research. METHODS: Using data from school-based randomized trial of an asthma intervention targeting urban adolescents, we compared percent poverty in zip code of residence (% poverty), median housing value, and parental income and education, to teen responses on the Home Affluence Scale for Children (HASC), which included home, car, and computer ownership for the family and eligibility for free school lunch. The association of HASC with measures of asthma control was also assessed. RESULTS: Of 422 adolescents, 390 (92%) responded to HASC items (mean HASC = 2.5). HASC was associated with mother's education and household income (both P < .001), and significantly correlated with % poverty (P < .0001) and median home value (P = .003). The association of HASC <2.0 to indicators of uncontrolled asthma was in the direction hypothesized, especially for nighttime symptoms, odds ratio (95% confidence interval) = 1.59 (0.95-2.66) and restricted activity, odds ratio = 1.87 (1.12-3.12). CONCLUSIONS: HASC correlates well with more traditional measures of SES, and the risk estimates for HASC less than 2.0 and indicators of uncontrolled asthma were mostly in the hypothesized direction. Methods of obtaining SES indicators from youth are needed for research studies.

Evaluation of a web-based asthma management intervention program for urban teenagers: reaching the hard to reach.

PURPOSE: Asthma interventions targeting urban adolescents are rare, despite a great need. Motivating adolescents to achieve better self-management of asthma is challenging, and the literature suggests that certain subgroups are more resistant than others. We conducted a school-based, randomized controlled trial (RCT) to evaluate Puff City, a Web-based, tailored asthma intervention, which included a referral coordinator, and incorporated theory-based strategies to target urban teens with characteristics previously found to be associated with lack of behavior change. METHODS: To identify eligible teens, we administered questionnaires on asthma diagnoses and symptoms to ninth through 12th graders of participating schools during a scheduled English class. We randomized eligible, consenting students to Puff City (treatment) or generic asthma education (control). RESULTS: We randomized 422 students (98% African-American, mean age = 15.6 years). At 12-month follow-up, adjusted odds ratios (aORs) (95% confidence intervals) indicated intervention benefit for treatment teens for symptom-days and restricted activity days (analyzed as categorical variables) as aOR = .49 (.24-.79), p = .006 and .53 (.32-.86), p = .010, respectively. Among teens meeting baseline criteria for rebelliousness, treatment teens reported fewer symptom-days, symptom-nights, school absences, and restricted activity days: aOR = .30 (.11-.80), .29 (.14-.64), .40 (.20-.78), and .23 (.10-.55); all p < .05. Among teens reporting low perceived emotional support, treatment students reported only fewer symptom-days than controls: aOR = .23 (.06-.88), p = .031. We did not observe statistically significant differences in medical care use. CONCLUSIONS: Results suggest that a theory-based, tailored approach, with a referral coordinator, can improve asthma management in urban teens. Puff City represents a viable strategy for disseminating an effective intervention to high-risk and hard-to-reach populations.

Exploring the impact of elevated depressive symptoms on the ability of a tailored asthma intervention to improve medication adherence among urban adolescents with asthma.

BACKGROUND: In patients with asthma, medication adherence is a voluntary behavior that can be affected by numerous factors. Depression is an important co-morbidity in adolescents with asthma that may significantly impact their controller medication adherence and other asthma-related outcomes. The modifying effect of depressive symptoms on an asthma intervention's ability to improve asthma controller medication adherence among urban adolescents with asthma has not yet been reported. OBJECTIVE: To assess self-reported symptoms of depression as an effect modifier of the relationship between randomization group and controller medication adherence at 6-month follow-up. METHODS: These analyses use data from a randomized controlled trial (RCT) conducted in Detroit high schools to evaluate a tailored asthma management program. The intervention included referrals to school or community resources for students reporting symptoms of depression and other issues. "Elevated depressive symptoms" was defined as a positive answer to ≥ 5 of 7 questions from a validated tool included on the baseline questionnaire. Self-reported adherence to controller medication was collected at intervention onset (session 1) and at 6-month follow up. Analyses were restricted to students with report of a controller medication at baseline. Logistic regression was used to assess elevated depressive symptoms as an effect modifier of the relationship between randomization group and 6-month adherence. RESULTS: Of the 422 students enrolled in the RCT, a controller medication was reported at intervention onset by n = 123 adolescents (29%). Analyzing this group, we observed an interaction between elevated depressive symptoms and adherence (p = 0.073). Stratified analysis showed better adherence in treatment group adolescents meeting criteria for elevated depressive symptoms at baseline as compared to the control group (adjusted Odds Ratio [aOR] = 9.50; p = 0.024). For adolescents without elevated depressive symptoms at baseline, differences in adherence by group assignment did not reach statistical significance (aOR 1.40, p = 0.49). CONCLUSIONS: In this sample of students reporting controller medications at baseline, report of elevated depressive symptoms at baseline and randomization to the intervention group was associated with significantly better adherence at 6-month follow up when compared to that of a control group. Larger studies are needed to evaluate the impact of depression on the relationship between adherence and asthma intervention effectiveness.

Effect of depressive symptoms on asthma intervention in urban teens.

BACKGROUND: The literature suggests that depression is an important comorbidity in asthma that can significantly influence disease management and quality of life (QOL). OBJECTIVE: To study the effect of coexisting depressive symptoms on the effectiveness of self-management interventions in urban teens with asthma. METHODS: We analyzed data from a randomized controlled trial of Puff City, a web-based, tailored asthma management intervention for urban teens, to determine whether depression modulated intervention effectiveness for asthma control and QOL outcomes. Teens and caregivers were classified as depressed based on responses collected from baseline questionnaires. RESULT: Using logistic regression analysis, we found that a lower percentage of treatment students had indicators of uncontrolled asthma compared with controls (adjusted odds ratios <1). However, for teens depressed at baseline, QOL scores at follow-up were significantly higher in the treatment group compared with the control group for the emotions domain (adjusted relative risk, 2.08; 95% confidence interval, 1.2-3.63; P = .01; interpreted as emotional QOL for treatment students increased by a factor of 2.08 above controls). Estimates for overall QOL and symptoms QOL were borderline significant (adjusted relative risk, 1.57; 95% confidence interval, 0.93-2.63; P = .09; and adjusted relative risk, 1.72; 95% confidence interval, 0.94-3.15; P = .08; respectively). Among teens not depressed at baseline, no significant differences were observed between treatment and control groups in QOL domains at follow-up. CONCLUSION: Our results suggest that depression modified the relationship between the effectiveness of an asthma intervention and emotional QOL in urban teens. Further assessment of self-management behavioral interventions for asthma should explore the mechanism by which depression may alter the intervention effect.

Tobacco smoke exposure and allergic sensitization in children: a propensity score analysis.

BACKGROUND AND OBJECTIVE: There is conflicting evidence of the effect of environmental tobacco smoke (ETS) on the development of allergic diseases in children. Studies have shown that this relationship differs depending on maternal history of the disease. We employed the rigour of propensity score methods to assess this relationship using data from a birth cohort. METHODS: Using n = 662 children from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, we assessed the relationship between early-life ETS and subsequent allergic sensitization via a positive skin prick test (SPT+) or at least one specific immunoglobulin E (IgE) ≥ 0.35 (sIgE+) in children aged 2-3 years. Propensity score estimation followed by full and nearest neighbour matching was compared with standard multivariable regression models. RESULTS: Among children without a maternal history of allergic disease, ETS was positively associated with allergic sensitization in children with an adjusted odds ratio (aOR) for SPT+ of 2.32 (95% confidence interval (CI): 1.28-4.22) and the aOR for sIgE+ was 2.53 (95% CI: 1.43-4.48). Contrarily, for children with a positive maternal history, the aOR for SPT+ and sIgE+ was 0.56 (95% CI: 0.24-1.32) and 0.43 (95% CI: 0.20-0.91), respectively. CONCLUSIONS: Using propensity score methods to rigorously control for confounding factors, ETS exposure was found to reduce the risk of allergic sensitization in children with a positive maternal history. There is a strong association between early-life ETS and the development of allergic sensitization for children aged 2-3 years without maternal history.

Dog allergen levels in homes with hypoallergenic compared with nonhypoallergenic dogs.

BACKGROUND: Despite the public interest in hypoallergenic dogs, few scientific, including epidemiological studies have attempted to evaluate claims of hypoallergenicity. This study was designed to determine whether dog breeds reported as hypoallergenic correspond to lower dog allergen in the home versus nonhypoallergenic dogs. METHODS: A web search was conducted to identify breeds cited as hypoallergenic. Four separate classification schemes using combinations of purebred and mixed breed dogs were used to compare the levels of Canis familiaris 1 in dust samples collected from homes with hypoallergenic versus nonhypoallergenic dogs from an established birth cohort. RESULTS: No classification scheme showed that the level of dog allergen in homes with hypoallergenic dogs differed from other homes. CONCLUSION: Dog-allergic individuals should have access to scientifically valid information on the level of allergen shedding of different breeds of dogs.

Comparison of early-, late-, and non-participants in a school-based asthma management program for urban high school students.

BACKGROUND: To assess bias and generalizability of results in randomized controlled trials (RCT), investigators compare participants to non-participants or early- to late-participants. Comparisons can also inform the recruitment approach, especially when working with challenging populations, such as urban adolescents. In this paper, we describe characteristics by participant status of urban teens eligible to participate in a RCT of a school-based, web-based asthma management program. METHODS: The denominator for this analysis was all students found to be eligible to participate in the RCT. Data were analyzed for participants and non-participants of the RCT, as well as for students that enrolled during the initially scheduled recruitment period (early-participants) and persons that delayed enrollment until the following fall when recruitment was re-opened to increase sample size (late-participants). Full Time Equivalents (FTEs) of staff associated with recruitment were estimated. RESULTS: Of 1668 teens eligible for the RCT, 386 enrolled early, and 36 enrolled late, leaving 1246 non-participants. Participants were younger (p < 0.01), more likely to be diagnosed, use asthma medication, and have moderate-to-severe disease than non-participants, odds ratios (95% Confidence Intervals) = 2.1(1.7-2.8), 1.7(1.3-2.1), 1.4(1.0-1.8), respectively. ORs were elevated for the association of late-participation with Medicaid enrollment, 1.9(0.7-5.1) and extrinsic motivation to enroll, 1.7(0.6-5.0). Late-participation was inversely related to study compliance for teens and caregivers, ORs ranging from 0.1 to 0.3 (all p-values < 0.01). Early- and late-participants required 0.45 FTEs/100 and 3.3 FTEs/100, respectively. CONCLUSIONS: Recruitment messages attracted youth with moderate-to-severe asthma, but extending enrollment was costly, resulting in potentially less motivated, and certainly less compliant, participants. Investigators must balance internal versus external validity in the decision to extend recruitment. Gains in sample size and external validity may be offset by the cost of additional staff time and the threat to internal validity caused by lower participant follow-up. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00201058.

Early complementary feeding and risk of food sensitization in a birth cohort.

BACKGROUND: Exposure to solid food or cow's milk (complementary food) before age 4 months may confer immune protection (tolerance) or detriment (allergy). OBJECTIVE: We explored the relationship between introduction of complementary food <4 months and IgE to egg, milk, and peanut allergen at 2 years in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort of Detroit, Mich. METHODS: At infant ages 1, 6, and 12 months, mothers were interviewed about feeding practices. Blood samples were collected at age 2 to 3 years to assess sensitization (IgE ≥ 0.35 IU/mL) to egg, milk, or peanut. RESULTS: For the 594 maternal-infant pairs analyzed, maternal mean age was 29.7 years, and 60.6% self-reported as African American or black. Infant exposure to complementary food <4 months was reported by 39.7% of mothers. IgE ≥0.35 IU/mL for egg, milk, or peanut allergen at age 2 years was observed in 23.9% (95% CI, 20.5% to 27.6%), 30.6% (26.9% to 34.5%), and 11.4% (8.9% to 14.3%) of children, respectively. The association between early feeding and sensitization was modified by parental history of asthma or allergy. In multivariable analysis, early feeding reduced the risk of peanut sensitization among children with a parental history (adjusted odds ratio, 0.2 [95% CI, 0.1-0.7]; P = .007). The relationship also became significant for egg when a cutoff for IgE of ≥0.70 IU/mL was used (adjusted odds ratio, 0.5 [95% CI, 0.3-0.9]; P = .022). CONCLUSION: In this cohort, complementary food introduced <4 months was associated with a reduced risk of peanut (and perhaps egg) sensitization by age 2 to 3 years, but only for children with a parental history of asthma or allergy.

Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus.

CONTEXT: Thiazolidinedione (TZD) use has recently been associated with an increased risk of fractures. OBJECTIVE: The aim of this study was to determine the time-dependent relationship between TZD use and fracture risk. DESIGN: We conducted a retrospective cohort study in a large health system in southeast Michigan. PATIENTS: PATIENTS who received care from the health system were included if they were at least 18 yr of age, had a diagnosis of diabetes, and had at least one prescription for an oral diabetes medication. These criteria identified 19,070 individuals (9,620 women and 9,450 men). INTERVENTION: This study compared patients treated with TZDs to patients without TZD treatment. Cox proportional hazard models were used to assess the relationship between exposure and outcomes. MAIN OUTCOME MEASURES: The primary outcome was the time to fracture. Secondary analyses examined the risk of fractures in subgroups defined by sex and age. RESULTS: TZD use was associated with an increased risk of fracture in the cohort overall [adjusted hazard ratio (aHR), 1.35; 95% confidence interval (CI), 1.05-1.71] and in women (aHR, 1.57; 95% CI, 1.16-2.14), but not in men (aHR, 1.05; 95% CI, 0.70-1.58). Women more than 65 yr of age appeared to be at greatest risk for fracture (aHR, 1.72; 95% CI, 1.17-2.52). Among women, the increased fracture risk was not apparent until after 1 yr of TZD treatment. CONCLUSIONS: TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients.

Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis.

PURPOSE: To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis. METHODS: We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality. RESULTS: 19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048). CONCLUSIONS: Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.

Differences in allergic sensitization by self-reported race and genetic ancestry.

BACKGROUND: Many allergic conditions occur more frequently in African American patients when compared with white patients; however, it is not known whether this represents genetic predisposition or disparate environmental exposures. OBJECTIVE: We sought to assess the relationship of self-reported race and genetic ancestry to allergic sensitization. METHODS: We included 601 women enrolled in a population-based cohort study whose self-reported race was African American or white. Genetic ancestry was estimated by using markers that differentiate West African and European ancestry. We assessed the relationship between allergic sensitization (defined as > or =1 allergen-specific IgE results) and both self-reported race and genetic ancestry. Regression models adjusted for sociodemographic variables, environmental exposures, and location of residence. RESULTS: The average proportion of West African ancestry in African American participants was 0.69, whereas the mean proportion of European ancestry in white participants was 0.79. Self-reported African American race was associated with allergic sensitization when compared with those who reported being white (adjusted odds ratio, 2.19; 95% CI, 1.22-3.93), even after adjusting for other variables. Genetic ancestry was not significantly associated with allergic sensitization after accounting for location of residence (adjusted odds ratio, 2.09 for urban vs suburban residence; 95% CI, 1.32-3.31). CONCLUSION: Self-reported race and location of residence appeared to be more important predictors of allergic sensitization when compared with genetic ancestry, suggesting that the disparity in allergic sensitization by race might be primarily a result of environmental factors rather than genetic differences.

Effects of baseline comorbidities on cancer screening trial adherence among older African American men.

BACKGROUND: The purpose of this study was to examine the effects of baseline comorbidities on screening adherence in a sample of older African American men (ages >or=55 years) enrolled in a case management intervention in a cancer screening trial. METHODS: Baseline comorbidity data were obtained from 683 African American men who were randomly assigned to a case management intervention group (n = 344) or to a case management control group (n = 339). The effects of comorbidities on the screening adherence rates of each group were then assessed. RESULTS: No statistically significant interactions were found between each health history characteristic and the intervention. Therefore, analyses were not stratified by intervention status. In general, participants with comorbidities were no less likely to adhere to trial screening than participants without comorbidities. Exceptions were current smokers and participants with chronic bronchitis. Current smokers were less likely than others to adhere to the prostate-specific antigen test (P = 0.02) and the digital rectal examination for prostate cancer screening (P = 0.01), to the chest X-ray for lung cancer screening (P < 0.01), and to the flexible sigmoidoscopy for colorectal cancer screening (P = 0.04). Participants with chronic bronchitis had lower rates of adherence to the chest X-ray (P = 0.06). Having a relative with cancer positively influenced adherence to the digital rectal examination (P = 0.05). CONCLUSIONS: Overall, older African American men with comorbidities appear to be very good candidates for participation in longitudinal cancer screening trials. However, smoking had a statistically significant and deleterious effect on adherence to all types of screening.