How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts.

The association between sex/gender and aging-related cognitive decline remains poorly understood because of inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to differential selection by dropout and death between men and women. We aimed to evaluate the impact of selection by dropout and death on the association between sex/gender and cognitive decline. We first compared the statistical methods most frequently used for longitudinal data, targeting either population estimands (marginal models fitted by generalized estimating equations) or subject-specific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 population-based studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Âgées QUID (PAQUID; 1988-2014), the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (2003-2016), the Three-City Study (Bordeaux only; 1999-2016), the Washington Heights-Inwood Community Aging Project (WHICAP; 1992-2017), and the Whitehall II Study (2007-2016)) and 2 clinic-based studies (the Alzheimer's Disease Neuroimaging Initiative (ADNI; 2004-2017) and a nationwide French cohort study, MEMENTO (2011-2016)). We illustrate differences in the estimands of the association between sex/gender and cognitive decline in selected examples and highlight the critical role of differential selection by dropout and death. Using the same estimand, we then contrast the sex/gender-cognitive decline associations across cohorts and cognitive measures suggesting a residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the living population for assessing sex/gender differences while handling differential selection over time.

Comparison of Biological Screening and Diagnostic Indicators to Detect In Utero Opiate and Cocaine Exposure Among Mother-Infant Dyads.

BACKGROUND: Opioid and cocaine antenatal substance use can result in significant obstetric and pediatric health implications. Accurate detection of in utero-exposed neonates can improve patient care and health outcomes. Therefore, the effectiveness of mother-infant biological and diagnostic indicators collected at labor and delivery to provide accurate detection of in utero opiate and cocaine exposure was assessed. METHODS: A retrospective medical chart review included 335 mother-infant dyads exposed to antenatal substances who were delivered between January 2009 and March 2014. Mother-infant dyads were a subset of a larger retrospective cohort of 560 substance-using mothers, who had a valid meconium drug screen (MDS) and anesthesia before delivery. Alternative biological and diagnostic indicators of maternal urine drug screens (UDS), maternal substance use International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and neonatal exposure diagnostic ICD-9-CM codes were compared against MDS. Data were analyzed using classification accuracy measures. RESULTS: Compared with MDS, maternal UDS had the highest sensitivity [0.52, 95% confidence interval (CI), 0.39-0.65] and specificity (0.88, 95% CI, 0.79-0.97) to detect intrauterine opiate exposure. Maternal substance use diagnosis had the highest sensitivity (0.39, 95% CI, 0.16-0.61) and maternal UDS had the highest specificity (1.00, 95% CI, 0.99-1.00) to detect intrauterine cocaine exposure. Cocaine exposure had significantly higher accuracy scores across detection methods compared with opiate exposure. CONCLUSIONS: Alternative indicators collected at delivery were ineffective at identifying in utero substance exposure, especially neonatal-exposed ICD-9-CM codes. Low sensitivity scores indicate that many exposed neonates could be misdiagnosed or left untreated. Accurate antenatal exposure identification at delivery is an important form of tertiary assessment that warrants the development of improved screening methodology and standardization of hospital biological drug testing.

Adverse Childhood Experiences and Chronic Low Back Pain in Adulthood: The Role of Emotion Regulation.

Chronic low back pain (cLBP) is characterized by biopsychosocial determinants that collectively result in a substantial burden at the individual, community, and health care system levels. A growing body of literature suggests that childhood adversity is longitudinally associated with the development and maintenance of various chronic pain conditions in adulthood. Little research has investigated the psychological processes that might underlie the association between adverse childhood experiences (ACEs) and cLBP. Emotion regulation comprises a substantive part of the subjective experience of pain and may be a potential mechanism through which ACEs contribute to cLBP etiology and maintenance. Thus, the current study examined the extent to which emotion dysregulation mediated the relationship between ACEs and pain severity (pain at rest and movement-evoked pain) in adults with cLBP. Participants included 183 adults (53.0% female, 62.5% non-Hispanic Black) between the ages of 18 and 85 with cLBP. Participants self-reported on ACEs, pain, difficulties in emotion regulation (DER), depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = .15 [95% CI {.06-.25}]) and with movement (indirect effect = 1.50 [95% CI {.69-2.57}]). Findings suggest ACEs are linked to cLBP severity in adulthood through DER. This aligns with research demonstrating that childhood maltreatment can lead to DER, which perpetuate over the lifespan to impact adult health outcomes. PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to cLBP in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention. TRIAL REGISTRATION: This study utilized baseline data collected as part of a parent trial titled "Examining Racial and SocioEconomic Disparities in Chronic Low Back Pain" (ClinicalTrials.gov ID: NCT03338192).

Neighborhood Socioeconomic Environment and Risk of Type 2 Diabetes: Associations and Mediation Through Food Environment Pathways in Three Independent Study Samples.

OBJECTIVE: We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: 1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); 2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and 3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract-level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of 1) fast-food restaurants and 2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural. RESULTS: Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE-diabetes associations were mediated through food-environment pathways. CONCLUSIONS: Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways.

Cryotherapy and topical minocycline as adjunctive measures to control pain after third molar surgery: an exploratory study.

PURPOSE: To assess the impact of cryotherapy or topical minocycline on patients' perceptions of recovery from pain after third molar surgery in an exploratory comparative-effectiveness study. PATIENTS AND METHODS: Subjects aged at least 14 years who were having all 4 third molars removed were enrolled in 3 separate institutional review board-approved studies. Study groups included subjects treated with a passively applied cold wrap for 24 hours postoperatively, subjects treated with topical minocycline during surgery, and subjects enrolled in a nonconcurrent comparison group who had received neither topical minocycline nor directed cryotherapy. Third molar surgery was performed in all cases by trained surgeons using the same protocol. An exact Kruskal-Wallis test was used to compare the distributions of the worst and average pain scores and a Fisher exact test to compare verbal responses from Gracely pain scales among the 3 groups for postsurgical days (PSDs) 1 to 3. RESULTS: This study comprised 51 cryotherapy subjects (2005-2009), 63 minocycline subjects (2003-2004), and 92 comparison-group subjects (2002-2006) who were treated at academic centers and in community practices across the United States (N = 206). Demographic descriptors were similar among all groups. For PSDs 1 through 3 (unadjusted), the highest scores for worst pain (6-7 [out of 7] on Likert-type scale) were reported less frequently in each of the study groups than in subjects in the comparison group, although the numbers of subjects reporting the highest scores were few. The distribution of pain outcomes was significantly different among the 3 groups for worst pain and affective words on PSD 1 (P = .04 for both). However, the small number of subjects who reported the highest pain scores precluded adequate multivariate statistical analyses for all outcomes on PSD 1 to 3. CONCLUSIONS: Data from this exploratory study suggest that adjunctive therapy to decrease postoperative pain-cryotherapy or topical minocycline-might be effective at moderating the patient's highest pain levels after third molar surgery. The topic should be studied further in a multicenter, prospective, randomized trial.

Correction: Association of baseline inflammatory biomarkers with cancer mortality in the REGARDS cohort.

[This corrects the article DOI: 10.18632/oncotarget.27108.].

Association of baseline inflammatory biomarkers with cancer mortality in the REGARDS cohort.

This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46-48.63); those in the highest tertile of IL-8 had over a 2-fold increased risk of cancer mortality (HR: 2.21, 95% CI: 0.86-5.71), while those in the highest tertile of IL-10 had over a 3-fold increased risk of cancer mortality (HR: 3.06, 95% CI: 1.35-6.89). In race-stratified analysis, each unit increase in IL-6 was associated with increased risk of cancer mortality among African-Americans (HR: 3.88, 95% CI: 1.17-12.88) and Whites (5.25, 95% CI: 1.24-22.31). If replicated in larger, racially diverse prospective cohorts, these results suggest that cancer patients may benefit from clinical or lifestyle approaches to regulate systemic inflammation as a cancer prevention strategy.

Can Adolescent Drivers' Motor Vehicle Crash Risk Be Reduced by Pre-Licensure Intervention?

PURPOSE: Although motor vehicle crashes are the leading cause of death for adolescents, there is a scarcity of research addressing adolescents' lack of pre-licensure practical driving experience, which is theorized to increase their post-licensure crash risk. METHODS: Utilizing police-reported crashes and survey data from a randomized and quasi-randomized trial (n = 458 adolescents, 16 or 17 years of age at enrollment), the impact of a parent-directed supervised practice driving intervention and a comprehensive on-road driving assessment (ODA) with feedback was evaluated on adolescent drivers' motor vehicle crashes involvement. RESULTS: Compared with the control condition, a nonsignificant 20% relative reduction in risk was observed for the parent-directed intervention: adjusted hazard ratio = .80 (95% confidence interval [CI] .44, 1.43); the unadjusted absolute risk reduction was 1.1% (95% CI -4.4, 7.1). Exposure to the ODA resulted in an 53% relative reduction of risk: adjusted hazard ratio = .47 (95% CI .24, .91); the unadjusted absolute risk reduction was 5.4% (95% CI -.3, 10.7). CONCLUSIONS: Comprehensive ODA might be protective for adolescents; however, additional research is needed.

Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality.

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality. METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score. RESULTS: Among 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 - 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 - 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality. CONCLUSIONS: Leptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study. IMPACT: Our observed increased risk of cancer mortality associated with higher serum resistin levels among Blacks suggests that if validated in larger cohorts, clinical strategies focused on resistin control may be a promising cancer prevention strategy.

Influence of powder composition and morphology on penetration of Gray and White ProRoot mineral trioxide aggregate and calcium hydroxide into dentin tubules.

This study examined the influence of powder composition and morphology on the penetration of Gray and White ProRoot mineral trioxide aggregate (GMTA, WMTA) and calcium hydroxide (CH) into open dentin tubules. GMTA, WMTA, and CH particle dimensions were analyzed by flow particle image analysis (FPIA). Penetration of open dentin tubules into dentin discs was studied by scanning electron microscopy. Five samples of each material were randomly selected and prepared for this study. The GMTA averages for length (µm), width (µm), perimeter (µm), and aspect ratio were 1.94 ± 1.65, 1.43 ± 1.19, 5.61 ± 4.27, and 0.76 ± 0.14, respectively. Corresponding averages for WMTA were 2.04 ± 1.87, 1.49 ± 1.33, 5.88 ± 4.81, and 0.76 ± 0.14, and for CH were 2.26 ± 1.99, 1.62 ± 1.46, 6.70 ± 5.60, and 0.74 ± 0.15, respectively. The rank order of the averages for particle length, width and perimeter from the largest to the smallest material was CH > WMTA > GMTA. The rank order of the averaged aspect ratios was GMTA > WMTA > CH. SEM showed that all three materials, when deposited and agitated on dentin discs, penetrated the open dentin tubules. Tubule occlusion occurred as particle surface concentrations increased. Significant differences in particle length, width, perimeter, and aspect ratio were observed for GMTA, WMTA, and CH (P < 0.0001 in all cases). All particle types penetrated into open tubules when agitated on dentin discs; all tubules were eventually occluded as particle concentrations grew. (J Oral Sci 56, 287-293, 2014).