Experiences of adversity in childhood and adolescence and cortisol in late adolescence.

Early life adversity influences the diurnal cortisol rhythm, yet the relative influence of different characteristics of adversity remains unknown. In this study, we examine how developmental timing (childhood vs. adolescence), severity (major vs. minor), and domain of early life adversity relate to diurnal cortisol rhythms in late adolescence. We assessed adversity retrospectively in early adulthood in a subsample of 236 participants from a longitudinal study of a diverse community sample of suburban adolescents oversampled for high neuroticism. We used multilevel modeling to assess associations between our adversity measures and the diurnal cortisol rhythm (waking and bedtime cortisol, awakening response, slope, and average cortisol). Major childhood adversities were associated with flatter daily slope, and minor adolescent adversities were associated with greater average daily cortisol. Examining domains of childhood adversities, major neglect and sexual abuse were associated with flatter slope and lower waking cortisol, with sexual abuse also associated with higher cortisol awakening response. Major physical abuse was associated with higher waking cortisol. Among adolescent adversities domains, minor neglect, emotional abuse, and witnessing violence were associated with greater average cortisol. These results suggest severity, developmental timing, and domain of adversity influence the association of early life adversity with stress response system functioning.

Early and current life adversity: Past and present influences on maternal diurnal cortisol rhythms during pregnancy.

Stress during pregnancy affects maternal health and well-being, as well as the health and well-being of the next generation, in part through the hypothalamic-pituitary-adrenal (HPA) axis. Although most studies have focused solely on proximal experiences (i.e., during the pregnancy) as sources of prenatal stress, there has been a recent surge in studies that examine maternal early life adversity as a source of stress system dysregulation during pregnancy. The current study of 178 pregnant women examined the association of economic and life stress experienced during two time periods (i.e., childhood and pregnancy) with maternal HPA axis activity during the third trimester of pregnancy. Findings indicated that a current annual income of less than $15,000 and greater childhood disadvantage were associated with a flatter diurnal cortisol slope. Childhood maltreatment, particularly sexual abuse, was associated with a higher cortisol awakening response (CAR), even when controlling for recent adversity. We found some evidence that past adversity moderates the relationship between current adversity and diurnal cortisol, specifically for economic adversity and waking cortisol. Overall, our findings indicate that early life stressors play an important and underappreciated role in shaping stress biology during pregnancy.

Early-life adversity severity, timing, and context type are associated with SLC6A4 methylation in emerging adults: Results from a prospective cohort study.

BACKGROUND: Epigenetic modifications, including DNA methylation (DNAm), can play a role in the biological embedding of early-life adversity (ELA) through serotonergic mechanisms. The current study examines methylation of the CpG island in the promoter region of the stress-responsive serotonin transporter gene (SLC6A4) and is the first to jointly assess how it is influenced by ELA severity, timing, and type-specifically, deprivation and threat. METHODS: We use data from 627 Youth Emotion Project study participants, recruited from two US high schools. Using adjusted linear regressions, we analyze DNA collected in early adulthood from 410 participants and ELA based on interviewer-rated responses from concurrent Childhood Trauma Interviews, adjusting for survey-measured covariates. RESULTS: ELA robustly predicted mean CpG island SLC6A4 DNAm percent across 71 CpG sites. Each additional major-severity ELA event was associated with a 0.121-percentage-point increase (p<0.001), equating to a 0.177 standard deviation (sd) higher DNAm level (95 % CI: 0.080, 0.274) with each 1-sd higher adversity score. When modeled separately, both childhood and adolescent ELA predicted SLC6A4 DNAm. When modeled jointly, adolescent ELA was most strongly predictive, and child adversity remained significantly associated with DNAm through indirect associations via adolescent adversity. Additionally, the ELA-SLC6A4 DNAm association may vary by adversity type. Across separate models for childhood and adolescent exposures, deprivation coefficients are positive and statistically significant. Meanwhile, threat coefficients are positive and not significantly significant but do not statistically differ from deprivation coefficients. In models including all ELA dimensions, one major adolescent deprivation event is associated with a 0.222-percentage-point increased SLC6A4 DNAm (p<0.05), or a 1-sd higher deprivation score with a 0.157-sd increased DNAm. CONCLUSION: Results further implicate epigenetic modification on serotonergic neurotransmission via DNAm in the downstream sequelae of ELA-particularly adolescent deprivation-and support preventive interventions in adolescence to mitigate biological embedding.

A window into racial and socioeconomic status disparities in preschool disciplinary action using developmental methodology.

There are large differences in expulsions and suspensions on the basis of race starting in preschool and divergent explanations for their cause. The current study explores how developmental methodology can shed light on this vexing issue. We leverage two measures: (1) childcare provider complaints about children's behavior and their recommended disciplinary action (measured by parent report); and (2) observed disruptive behavior measured by a laboratory-based standardized observation tool, the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS), among a large, sociodemographically diverse sample of children (n  =$\text{=}$  430; mean age  =$\text{=}$  4.79 years). We identified three latent class profiles on the basis of race/socioeconomic status (SES) and found disparities in childcare provider complaints based on profile membership. More specifically, children classified in the Black/Hispanic, poor and Black, nonpoor profiles both had significantly higher childcare provider complaints compared with children in the White/Hispanic, nonpoor profile. By contrast, there were no differences in observed disruptive behavior based on race/SES profiles. Finally, childcare provider complaints in preschool were associated with lower cognitive performance in elementary school, above and beyond observed disruptive behavior in preschool and race/SES profiles. Implications for classroom practice and contributions to the national debate on school disciplinary policies are discussed.

Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample.

OBJECTIVE: We sought to estimate the impact of knee osteoarthritis (OA) on health care utilization. RESEARCH DESIGN: Using the 2003 Medicare Current Beneficiary Survey, a population-based survey of Medicare beneficiaries linked to Medicare claims, we selected a national cohort of community-dwelling persons aged 65 and older with knee OA and a sex- and age-matched comparison cohort without any form of OA. We distinguished following 4 components of health care utilization: physician (MD) office visits, non-MD office visits, inpatient hospital stays, and emergency department visits. We built multiple regression models to determine whether knee OA affects utilization, controlling for comorbidity count, obesity, functional limitation, education, race, and working status. RESULTS: A total of 545 Medicare Current Beneficiary Survey participants with knee OA were matched with 1090 OA-free individuals. Mean age in both cohorts was 76 years; approximately 70% were female. Knee OA and OA-free subjects differed significantly in obesity (Knee OA: 37%, OA-free: 20%), % with >or=2 comorbidities (Knee OA: 69%, OA-free: 43%), and functional limitation (Knee OA: 42%, OA-free: 26%). In multivariable regression models, the knee OA cohort had on average 6.0 more annual MD visits (95% confidence interval [CI]: 4.7, 7.4) and 3.8 more non-MD visits (95% CI: 2.8, 4.7) than the OA-free cohort. The knee OA cohort also had 28% more hospital stays (odds ratio [OR] = 1.3, 95% CI: 1.0, 1.6), a difference attributable to total joint replacements. CONCLUSIONS: This first national, population-based study of health care utilization in persons with knee OA documents considerable excess utilization attributable to knee OA, independent of comorbidity, and other patient characteristics.

Neighborhoods matter: use of hospitals with worse outcomes following total knee replacement by patients from vulnerable populations.

BACKGROUND: Neighborhood sociodemographic characteristics are associated with health care utilization across many conditions. There has been little study of whether total knee replacement (TKR) recipients from vulnerable populations, including racial and ethnic minorities, the poor, the elderly, and the less well educated, are more likely to use low-volume hospitals (LVHs). METHODS: We used Medicare claims and census data to identify a national cohort of Medicare beneficiaries who had elective TKR. We defined an LVH as a center performing fewer than 26 TKRs per year, and we used geocoding to identify "bypassers" (patients who had a high-volume hospital closer to their residence than the one where they had TKR). We used multivariate logistic regression to examine the association of patient and neighborhood characteristics with utilization of LVHs and bypassing. We derived a summative measure of neighborhood vulnerability that included 4 high-risk characteristics (factors were high proportions of residents who are minority individuals, who have foreign-born status, with low income, and with low education). RESULTS: Of 113 015 TKR recipients, 13 120 (11.6%) used LVHs. Of all the TKR recipients, 9815 (8.7%) bypassed a center with a higher TKR volume than the one they used. Multivariate analyses showed that nonwhite (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.16-1.33), poor (OR, 1.94; 95% CI, 1.83-2.08), and nonurban (OR, 1.94; 95% CI, 1.87-2.01) subjects were more likely to use LVHs. The TKR recipients from neighborhoods with 3 or 4 vulnerability factors were more likely than patients in neighborhoods with no vulnerability factors to use an LVH and bypass a high-volume hospital. CONCLUSION: Efforts to inform patients about the association of volume with TKR outcomes should target rural areas and vulnerable populations in urban settings.

Professionalism and evolving concepts of quality.

For much of the twentieth century, quality of care was defined specifically in terms of physician characteristics and behaviors. High-quality physicians were well trained, knowledgeable, skillful, and compassionate. More recently, quality of care has been defined in terms of systems of care. High-quality organizations develop and adopt practices to reduce adverse events and optimize outcomes. This essay discusses this transformation from physician-based to organization-based concepts of quality and the consequences for patient care and medical professionalism.

Cervical cancer screening in the United States, 1993-2010: characteristics of women who are never screened.

BACKGROUND: Regular Pap test screening has contributed to decreasing cervical cancer incidence and mortality over the past decades, yet half of the women diagnosed with cervical cancer have never had a Pap test. Our study aims to examine the cervical cancer screening rate, identify socioeconomic and demographic risk factors associated with adult women who have never had a Pap test, and examine the relationship of screening with use of related health services. METHODS: Using Behavioral Risk Factor Surveillance System data (1993-2010), a multivariable survey logistic regression model was fitted to estimate odds ratios for associations between risk factors and the outcome of never screened. RESULTS: Between 1993 and 2010, 81.3% of respondents reported they had a Pap test within 3 years; 6.2% were never screened. For women who had a recent checkup, 5.5% were never screened. Among women who had a hysterectomy, 69.4% had a Pap test within 3 years. The multivariable analysis showed that age, race/ethnicity, education, annual household income, never married, and currently uninsured were significantly (p<0.001) associated with never screened. CONCLUSIONS: Screening programs accompanied by adequate treatment options should target women at high risk for never being screened, which could decrease cervical cancer incidence and mortality.

Determinants of self-reported health status in a population-based sample of persons with radiographic knee osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) is highly prevalent and disabling. Patients with radiographic knee OA may experience pain and functional impairment, which can diminish their health status. Our objective was to determine factors associated with self-reported health status in a national population-based sample with radiographic knee OA. METHODS: Our sample included all of the Third National Health and Nutrition Examination Survey (NHANES-III) participants who underwent a knee radiograph and were found to have radiographic OA (defined as Kellgren/Lawrence grade 2 or higher). Self-reported health status was determined by asking the participant to rate their overall health as excellent, very good, good, fair, or poor. Self-reported health status was analyzed as an ordinal variable using cumulative logit regression, as a dichotomous variable (excellent/very good/good versus fair/poor) using logistic regression, and as a continuous variable after transformation using linear regression. RESULTS: A total of 1,021 (42%) of NHANES-III participants with a knee radiograph were included in this analysis. The multivariable analyses were performed on 1,009 (99%) of the eligible participants with complete data. We found that nonwhite race, lower income, more comorbidities, and greater functional limitation were associated with worse self-reported health status in all 3 multivariable analyses. CONCLUSION: This study has quantified the role of clinical, radiographic, and socioeconomic factors associated with self-reported health status in a population-based sample of patients with knee OA. Self-reported health status in patients with knee OA was associated with functional status and comorbidity.

Cost-effectiveness of total knee arthroplasty in the United States: patient risk and hospital volume.

BACKGROUND: Total knee arthroplasty (TKA) relieves pain and improves quality of life for persons with advanced knee osteoarthritis. However, to our knowledge, the cost-effectiveness of TKA and the influences of hospital volume and patient risk on TKA cost-effectiveness have not been investigated in the United States. METHODS: We developed a Markov, state-transition, computer simulation model and populated it with Medicare claims data and cost and outcomes data from national and multinational sources. We projected lifetime costs and quality-adjusted life expectancy (QALE) for different risk populations and varied TKA intervention and hospital volume. Cost-effectiveness of TKA was estimated across all patient risk and hospital volume permutations. Finally, we conducted sensitivity analyses to determine various parameters' influences on cost-effectiveness. RESULTS: Overall, TKA increased QALE from 6.822 to 7.957 quality-adjusted life years (QALYs). Lifetime costs rose from $37,100 (no TKA) to $57 900 after TKA, resulting in an incremental cost-effectiveness ratio of $18,300 per QALY. For high-risk patients, TKA increased QALE from 5.713 to 6.594 QALY, yielding a cost-effectiveness ratio of $28,100 per QALY. At all risk levels, TKA was more costly and less effective in low-volume centers than in high-volume centers. Results were insensitive to variations of key input parameters within policy-relevant, clinically plausible ranges. The greatest variations were seen for the quality of life gain after TKA and the cost of TKA. CONCLUSIONS: Total knee arthroplasty appears to be cost-effective in the US Medicare-aged population, as currently practiced across all risk groups. Policy decisions should be made on the basis of available local options for TKA. However, when a high-volume hospital is available, TKAs performed in a high-volume hospital confer even greater value per dollar spent than TKAs performed in low-volume centers.

Geographic diversity of low-volume hospitals in total knee replacement: implications for regionalization policies.

BACKGROUND/OBJECTIVES: Centers performing low volumes of total knee replacements (TKR) have worse outcomes of TKR than higher volume centers. Regionalization policies that shift patients to higher volume centers are being considered as a means of improving TKR outcomes. We sought to describe geographic diversity in the distribution of low-volume centers and examine state level characteristics associated with states that have a higher proportion of low-volume centers and/or a higher proportion of TKRs performed in low-volume centers. METHODS: We used U.S. Census data and geocoded Medicare claims to ascertain state-level demographic factors, procedure volume, and TKR rates and to conduct our state level analysis. We defined 2 outcomes: 1) proportion of all hospitals with a low annual TKR volume (<26 per year in the Medicare population); and 2) proportion of all TKRs in the Medicare population performed in low-volume centers. We examined linear associations among the 2 outcomes and state factors, and used multivariate regression to identify factors associated independently with these outcomes. RESULTS: Half of hospitals performing TKR in the Medicare population were low-volume centers, accounting for 13% of TKRs. Multivariate analysis revealed lower TKR rates, higher proportion of rural areas and larger state area were associated with a higher proportion of low-volume hospitals in a state. Lower proportion of elderly residents, higher population density and higher proportion of rural areas predicted a higher proportion of TKRs performed in low-volume centers. CONCLUSIONS: The distribution of low-volume hospitals among U.S. states varies substantially. Regionalization of TKR may require different strategies in states with small and large numbers of low-volume centers.