Changes in Buprenorphine Prescribing in Community Health Centers.

This cohort study characterizes changes in buprenorphine prescribing among community health center clinicians between 2016 and 2021.

Impact of Health Insurance Patterns on Chronic Health Conditions Among Older Patients.

BACKGROUND: Patients have varying levels of chronic conditions and health insurance patterns as they become Medicare age-eligible. Understanding these dynamics will inform policies and reforms that direct capacity and resources for primary care clinics to care for these aging patients. This study 1) determined changes in chronic condition rates following Medicare age eligibility among patients with different insurance patterns and 2) estimated the number of chronically ill patients who remain inadequately insured post-Medicare eligibility among patients receiving care in community health centers. METHOD: We used retrospective electronic health record data from 45,527 patients aged 62 to 68 from 990 community health centers in 25 states in 2014 to 2019. Insurance patterns (continuously insured, continuously uninsured, uninsured/discontinuously insured who gained insurance after age 65, lost insurance after age 65, discontinuously insured) and diagnosis of chronic conditions were defined at each visit pre- and post-Medicare eligibility. Difference-in-differences Poisson GEE models estimated changes of chronic condition rates by insurance groups pre- to post-Medicare age eligibility. RESULTS: Post-Medicare eligibility, 72% patients were continuously insured, 14% gained insurance; and 14% were uninsured or discontinuously insured. The prevalence of multimorbidity (≥2 chronic conditions) was 77%. Those who gained insurance had a significantly larger increase in the rate of documented chronic conditions from pre- to post-Medicare (DID: 1.06, 95%CI:1.05-1.07) compared with the continuously insured group. CONCLUSIONS: Post-Medicare age eligibility, a significant proportion of patients were diagnosed with new conditions leading to high burden of disease. One in 4 older adults continue to have inadequate health care coverage in their older age.

Chronic overlapping pain conditions and long-term opioid treatment.

OBJECTIVES: One in 5 people in the United States lives with chronic pain. Many patients with chronic pain experience a subset of specific co-occurring pain conditions that may share a common pain mechanism and that have been designated as chronic overlapping pain conditions (COPCs). Little is known about chronic opioid prescribing patterns among patients with COPCs in primary care settings, especially among socioeconomically vulnerable patients. This study aims to evaluate opioid prescribing among patients with COPCs in US community health centers and to identify individual COPCs and their combinations that are associated with long-term opioid treatment (LOT). STUDY DESIGN: Retrospective cohort study. METHODS: We conducted analyses of more than 1 million patients 18 years and older based on electronic health record data from 449 US community health centers across 17 states between January 1, 2009, and December 31, 2018. Logistic regression models were used to assess the relationship between COPCs and LOT. RESULTS: Individuals with COPCs were prescribed LOT 4 times more often than individuals without a COPC (16.9% vs 4.0%). The presence of chronic low back pain, migraine headache, fibromyalgia, or irritable bowel syndrome combined with any of the other COPCs increased the odds of LOT prescribing compared with the presence of a single COPC. CONCLUSIONS: Although LOT prescribing has declined over time, it remains relatively high among patients with certain COPCs and for those with multiple COPCs. These study findings suggest target populations for future interventions to manage chronic pain among socioeconomically vulnerable patients.

Sedative-hypnotic Co-prescribing with Opioids in a Large Network of Community Health Centers.

OBJECTIVE: When prescribed with opioids, sedative-hypnotics substantially increase the risk of overdose. The objective of this paper was to describe characteristics and trends in opioid sedative-hypnotic co-prescribing in a network of safety-net clinics serving low-income, publicly insured, and uninsured individuals. METHODS: This retrospective longitudinal analysis of prescription orders examined opioid sedative-hypnotic co-prescribing rates between 2009 and 2018 in the OCHIN network of safety-net community health centers. Sedative-hypnotics included benzodiazepine and non-benzodiazepine sedatives (eg, zolpidem). Co-prescribing patterns were assessed overall and across patient demographic and co-morbidity characteristics. RESULTS: From 2009 to 2018, 240 587 patients had ≥1 opioid prescriptions. Most were White (65%), female (59%), and had Medicaid insurance (43%). One in 4 were chronic opioid users (25%). During this period, 55 332 (23%) were co-prescribed a sedative-hypnotic. The prevalence of co-prescribing was highest for females (26% vs 19% for males), non-Hispanic Whites (28% vs 13% for Hispanic to 20% for unknown), those over 44 years of age (25% vs 20% for <44 years), Medicare insurance (30% vs 21% for uninsured to 22% for other/unknown), and among those on chronic opioid therapy (40%). Co-prescribing peaked in 2010 (32%) and declined steadily through 2018 (20%). Trends were similar across demographic subgroups. Co-prescribed sedative-hypnotics remained elevated for those with chronic opioid use (27%), non-Hispanic Whites (24%), females (23%), and those with Medicare (23%) or commercial insurance (22%). CONCLUSIONS: Co-prescribed sedative-hypnotic use has declined steadily since 2010 across all demographic subgroups in the OCHIN population. Concurrent use remains elevated in several population subgroups.

Factors Associated With Blood Pressure Control Among Patients in Community Health Centers.

INTRODUCTION: Understanding the multilevel factors associated with controlled blood pressure is important to determine modifiable factors for future interventions, especially among populations living in poverty. This study identified clinically important factors associated with blood pressure control among patients receiving care in community health centers. METHODS: This study includes 31,089 patients with diagnosed hypertension by 2015 receiving care from 103 community health centers; aged 19-64 years; and with ≥1 yearly visit with ≥1 recorded blood pressure in 2015, 2016, and 2017. Blood pressure control was operationalized as an average of all blood pressure measurements during all the 3 years and categorized as controlled (blood pressure <140/90), partially controlled (mixture of controlled and uncontrolled blood pressure), or never controlled. Multinomial mixed-effects logistic regression models, conducted in 2022, were used to calculate unadjusted ORs and AORs of being in the never- or partially controlled blood pressure groups versus in the always-controlled group. RESULTS: A total of 50.5% had always controlled, 39.7% had partially controlled, and 9.9% never had controlled blood pressure during the study period. The odds of being partially or never in blood pressure control were higher for patients without continuous insurance (AOR=1.09; 95% CI=1.03, 1.16; AOR=1.18; 95% CI=1.07, 1.30, respectively), with low provider continuity (AOR=1.24; 95% CI=1.15, 1.34; AOR=1.28; 95% CI=1.13, 1.45, respectively), with a recent diagnosis of hypertension (AOR=1.34; 95% CI=1.20, 1.49; AOR=1.19; 95% CI=1.00, 1.42), with inconsistent antihypertensive medications (AOR=1.19; 95% CI=1.11, 1.27; AOR=1.26; 95% CI=1.13, 1.41, respectively), and with fewer blood pressure checks (AOR=2.14; 95% CI=1.97, 2.33; AOR=2.17; 95% CI=1.90, 2.48, respectively) than for their counterparts. CONCLUSIONS: Efforts targeting continuous and consistent access to care, antihypertensive medications, and regular blood pressure monitoring may improve blood pressure control among populations living in poverty.

Affordable Care Act Medicaid expansion and access to primary-care based smoking cessation assistance among cancer survivors: an observational cohort study.

BACKGROUND: Smoking among cancer survivors can increase the risk of cancer reoccurrence, reduce treatment effectiveness and decrease quality of life. Cancer survivors without health insurance have higher rates of smoking and decreased probability of quitting smoking than cancer survivors with health insurance. This study examines the associations of the Affordable Care Act (ACA) Medicaid insurance expansion with smoking cessation assistance and quitting smoking among cancer survivors seen in community health centers (CHCs). METHODS: Using electronic health record data from 337 primary care community health centers in 12 states that expanded Medicaid eligibility and 273 CHCs in 8 states that did not expand, we identified adult cancer survivors with a smoking status indicating current smoking within 6 months prior to ACA expansion in 2014 and ≥ 1 visit with smoking status assessed within 24-months post-expansion. Using an observational cohort propensity score weighted approach and logistic generalized estimating equation regression, we compared odds of quitting smoking, having a cessation medication ordered, and having ≥6 visits within the post-expansion period among cancer survivors in Medicaid expansion versus non-expansion states. RESULTS: Cancer survivors in expansion states had higher odds of having a smoking cessation medication order (adjusted odds ratio [aOR] = 2.54, 95%CI = 1.61-4.03) and higher odds of having ≥6 office visits than those in non-expansion states (aOR = 1.82, 95%CI = 1.22-2.73). Odds of quitting smoking did not differ significantly between patients in Medicaid expansion versus non-expansion states. CONCLUSIONS: The increased odds of having a smoking cessation medication order among cancer survivors seen in Medicaid expansion states compared with those seen in non-expansion states provides evidence of the importance of health insurance coverage in accessing evidence-based tobacco treatment within CHCs. Continued research is needed to understand why, despite increased odds of having a cessation medication prescribed, odds of quitting smoking were not significantly higher among cancer survivors in Medicaid expansion states compared to non-expansion states.

Primary and mental health service use in community health center patients before and after cancer diagnosis.

BACKGROUND: Cancer survivors face increased risk for chronic diseases resulting from cancer, preexisting conditions, and cancer treatment. Having an established primary care clinic or health insurance may influence patients' receipt of recommended preventive care necessary to manage, treat, or diagnose new conditions. This study sought to understand receipt of healthcare in community health centers (CHCs) before and after cancer diagnosis among cancer survivors. We also examined the type of care received and assessed whether being established with a CHC or the type of health insurance affected the use of services. METHODS: Using electronic health record data and linked cancer registries from 5,649 CHC patients in three states from 2012 through 2018, we obtained monthly rates of primary care and mental health/behavioral health (MHBH) visits and the probability of receipt of care before and after a cancer diagnosis. RESULTS: Seventy-five percent of CHC patients diagnosed with cancer returned to their primary CHC for care within 2-years of their diagnosis. Among those who returned, there was a sharp increase in primary and MHBH care shortly before their diagnosis. Significantly more primary care (pre: 19.6%, post: 21.9%, p < 0.001) and MHBH care (pre: 1.2%, post: 1.6%, p < 0.001) was received after diagnosis than before. However, uninsured patients had fewer visits after their diagnosis than before. CONCLUSION: Use of preventive care for cancer survivors is particularly important. Having an established primary care clinic may help to ensure survivors receive recommended screening and care.

Comparing ascertainment of chronic condition status with problem lists versus encounter diagnoses from electronic health records.

OBJECTIVE: To assess and compare electronic health record (EHR) documentation of chronic disease in problem lists and encounter diagnosis records among Community Health Center (CHC) patients. MATERIALS AND METHODS: We assessed patient EHR data in a large clinical research network during 2012-2019. We included CHCs who provided outpatient, older adult primary care to patients age ≥45 years, with ≥2 office visits during the study. Our study sample included 1 180 290 patients from 545 CHCs across 22 states. We used diagnosis codes from 39 Chronic Condition Warehouse algorithms to identify chronic conditions from encounter diagnoses only and compared against problem list records. We measured correspondence including agreement, kappa, prevalence index, bias index, and prevalence-adjusted bias-adjusted kappa. RESULTS: Overlap of encounter diagnosis and problem list ascertainment was 59.4% among chronic conditions identified, with 12.2% of conditions identified only in encounters and 28.4% identified only in problem lists. Rates of coidentification varied by condition from 7.1% to 84.4%. Greatest agreement was found in diabetes (84.4%), HIV (78.1%), and hypertension (74.7%). Sixteen conditions had <50% agreement, including cancers and substance use disorders. Overlap for mental health conditions ranged from 47.4% for anxiety to 59.8% for depression. DISCUSSION: Agreement between the 2 sources varied substantially. Conditions requiring regular management in primary care settings may have a higher agreement than those diagnosed and treated in specialty care. CONCLUSION: Relying on EHR encounter data to identify chronic conditions without reference to patient problem lists may under-capture conditions among CHC patients in the United States.

Characterizations of Opioid Prescribing in Community Health Centers in 2018.

OBJECTIVE: To identify the patient- and clinic-level correlates of any prescription opioid use, chronic use, and high-dose opioid use in a multi-state network of Community Health Centers (CHCs). METHODS: We used electronic health record data from 337 primary care clinics serving 610 983 patients across 15 states in 2018. The primary outcomes were prescription of any opioid, chronic opioid, and high-dose opioid. RESULTS: Overall, 6.5% of patients were prescribed an opioid; of these, 31% were chronic users and 5% were high-dose users. Males had 5% lower odds (Odds Ratio [OR] = 0.95; 95% Confidence Interval = 0.93-0.97) of being prescribed an opioid but 16% higher odds (OR = 1.16; 95% CI = 1.10-1.21) of being chronic users and 48% (OR = 1.48; 95% CI = 1.36-1.64) higher odds of being high-dose users than females. Rural clinics had higher rates of chronic opioid (rate ratio = 1.86; 95% CI = 1.20, 2.88) and high-dose users (rate ratio = 2.95; 95% CI = 1.81-4.81). CONCLUSIONS: Our study highlights variations in opioid prescribing with regard to patient-level and clinic-level factors. Targeted efforts and resources may be required to support rural CHCs who seek to reduce high-risk opioid prescribing.

Prevalent Multimorbidity Combinations Among Middle-Aged and Older Adults Seen in Community Health Centers.

BACKGROUND: Multimorbidity (≥ 2 chronic diseases) is associated with greater disability and higher treatment burden, as well as difficulty coordinating self-management tasks for adults with complex multimorbidity patterns. Comparatively little work has focused on assessing multimorbidity patterns among patients seeking care in community health centers (CHCs). OBJECTIVE: To identify and characterize prevalent multimorbidity patterns in a multi-state network of CHCs over a 5-year period. DESIGN: A cohort study of the 2014-2019 ADVANCE multi-state CHC clinical data network. We identified the most prevalent multimorbidity combination patterns and assessed the frequency of patterns throughout a 5-year period as well as the demographic characteristics of patient panels by prevalent patterns. PARTICIPANTS: The study included data from 838,642 patients aged ≥ 45 years who were seen in 337 CHCs across 22 states between 2014 and 2019. MAIN MEASURES: Prevalent multimorbidity patterns of somatic, mental health, and mental-somatic combinations of 22 chronic diseases based on the U.S. Department of Health and Human Services Multiple Chronic Conditions framework: anxiety, arthritis, asthma, autism, cancer, cardiac arrhythmia, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), congestive heart failure, coronary artery disease, dementia, depression, diabetes, hepatitis, human immunodeficiency virus (HIV), hyperlipidemia, hypertension, osteoporosis, post-traumatic stress disorder (PTSD), schizophrenia, substance use disorder, and stroke. KEY RESULTS: Multimorbidity is common among middle-aged and older patients seen in CHCs: 40% have somatic, 6% have mental health, and 24% have mental-somatic multimorbidity patterns. The most frequently occurring pattern across all years is hyperlipidemia-hypertension. The three most frequent patterns are various iterations of hyperlipidemia, hypertension, and diabetes and are consistent in rank of occurrence across all years. CKD-hyperlipidemia-hypertension and anxiety-depression are both more frequent in later study years. CONCLUSIONS: CHCs are increasingly seeing more complex multimorbidity patterns over time; these most often involve mental health morbidity and advanced cardiometabolic-renal morbidity.

CACHD1-deficient mice exhibit hearing and balance deficits associated with a disruption of calcium homeostasis in the inner ear.

CACHD1 recently was shown to be an α2δ-like subunit that can modulate the activity of some types of voltage-gated calcium channels, including the low-voltage activated, T-type CaV3 channels. CACHD1 is widely expressed in the central nervous system but its biological functions and relationship to disease states are unknown. Here, we report that mice with deleterious Cachd1 mutations are hearing impaired and have balance defects, demonstrating that CACHD1 is functionally important in the peripheral auditory and vestibular organs of the inner ear. The vestibular dysfunction of Cachd1 mutant mice, exhibited by leaning and head tilting behaviors, is related to a deficiency of calcium carbonate crystals (otoconia) in the saccule and utricle. The auditory dysfunction, shown by ABR threshold elevations and reduced DPOAEs, is associated with reduced endocochlear potentials and increased endolymph calcium concentrations. Paint-fills of mutant inner ears from prenatal and newborn mice revealed dilation of the membranous labyrinth caused by an enlarged volume of endolymph. These pathologies all can be related to a disturbance of calcium homeostasis in the endolymph of the inner ear, presumably caused by the loss of CACHD1 regulatory effects on voltage-gated calcium channel activity. Cachd1 expression in the cochlea appears stronger in late embryonic stages than in adults, suggesting an early role in establishing endolymph calcium concentrations. Our findings provide new insights into CACHD1 function and suggest the involvement of voltage-gated calcium channels in endolymph homeostasis, essential for normal auditory and vestibular function.

Assessing Cancer History Accuracy in Primary Care Electronic Health Records Through Cancer Registry Linkage.

BACKGROUND: Many cancer survivors receive primary care in community health centers (CHCs). Cancer history is an important factor to consider in the provision of primary care, yet little is known about the completeness or accuracy of cancer history data contained in CHC electronic health records (EHRs). METHODS: We probabilistically linked EHR data from more than1.5 million adult CHC patients to state cancer registries in California, Oregon, and Washington and estimated measures of agreement (eg, kappa, sensitivity, specificity). We compared demographic and clinical characteristics of cancer patients as estimated by each data source, evaluating distributional differences with absolute standardized mean differences. RESULTS: A total 74 707 cancer patients were identified between the 2 sources (EHR only, n = 22 730; registry only, n = 23 616; both, n = 28 361). Nearly one-half of cancer patients identified in registries were missing cancer documentation in the EHR. Overall agreement of cancer ascertainment in the EHR vs cancer registries (gold standard) was moderate (kappa = 0.535). Cancer site-specific agreement ranged from substantial (eg, prostate and female breast; kappa > 0.60) to fair (melanoma and cervix; kappa < 0.40). Comparing population characteristics of cancer patients as ascertained from each data source, groups were similar for sex, age, and federal poverty level, but EHR-recorded cases showed greater medical complexity than those ascertained from cancer registries. CONCLUSIONS: Agreement between EHR and cancer registry data was moderate and varied by cancer site. These findings suggest the need for strategies to improve capture of cancer history information in CHC EHRs to ensure adequate delivery of care and optimal health outcomes for cancer survivors.

Assessment of Opioid Prescribing Patterns in a Large Network of US Community Health Centers, 2009 to 2018.

Importance: Understanding opioid prescribing patterns in community health centers (CHCs) that disproportionately serve low-income patients may help to guide strategies to reduce opioid-related harms. Objective: To assess opioid prescribing patterns between January 1, 2009, and December 31, 2018, in a network of safety-net clinics serving high-risk patients. Design, Setting, and Participants: Cross-sectional study of 3 227 459 opioid prescriptions abstracted from the electronic health records of 2 129 097 unique primary care patients treated from 2009 through 2018 at a network of CHCs that included 449 clinic sites in 17 states. All age groups were included in the analysis. Main Outcomes and Measures: The following measures were described at the population level for each study year: (1) percentage of patients with at least 1 prescription for an opioid by age and sex, (2) number of opioid prescriptions per 100 patients, (3) number of long-acting opioid prescriptions per 100 patients, (4) mean annual morphine milligram equivalents (MMEs) per patient, (5) mean MME per prescription, (6) number of chronic opioid users, and (7) mean of high-dose opioid users. Results: The study population included 2 129 097 patients (1 158 413 women [54.4%]) with a mean (SD) age of 32.2 (21.1) years and a total of 3 227 459 opioid prescriptions. The percentage of patients receiving at least 1 opioid prescription in a calendar year declined 67.4% from 15.9% in 2009 to 5.2% in 2018. Over the 10-year study period, a greater percentage of women received a prescription (13.1%) compared with men (10.9%), and a greater percentage of non-Hispanic White patients (18.1%) received an opioid prescription compared with non-Hispanic Black patients (9.5%), non-Hispanic patients who self-identified as other races (8.0%), and Hispanic patients (6.9%). The number of opioid prescriptions for every 100 patients decreased 73.7% from 110.8 in 2009 to 29.1 in 2018. The number of long-acting opioids for every 100 patients decreased 85.5% during the same period, from 22.0 to 3.2. The MMEs per patient decreased from 1682.7 in 2009 to 243.1 in 2018, a decline of 85.6%. Conclusions and Relevance: In this cross-sectional study, the opioid prescribing rate in 2009 in the CHC network was higher than national population estimates but began to decline earlier and more precipitously. This finding likely reflects harm mitigation policies and efforts at federal, state, and clinic levels and strong clinical quality improvement strategies within the CHCs.

Physical, Chemical, and Biological Factors that Contribute to the Variability of Mercury Concentrations in Largemouth Bass Micropterus salmoides from Missouri Reservoirs.

Large-bodied predatory sportfish from Missouri reservoirs can contain elevated methylmercury concentrations that are of concern to the health of consumers. The concentration of total mercury (tHg) in the muscle (which > 95% is in the methylated-Hg form) of harvestable-sized largemouth bass (Micropterus salmoides; LMB) was examined to determine which factors contributed to the variability of tHg concentration in sportfish populations among Missouri reservoirs. Mean tHg concentrations in LMB from each reservoir were compared to physical and chemical characteristics of the reservoir and to biological attributes of each LMB population. Low concentrations of tHg (70-170 ng/g wet weight) in LMB from large reservoirs (surface area ≥ 35,680 acres) were likely related to the dilution of chemical Hg forms with water volume and depth. The highest tHg concentrations in LMB (268-542 ng/g) were from reservoirs with low particulate inorganic material (< 1.5 mg/L) and chlorophyll a concentrations (< 14.6 µg/L), and from LMB populations with a low proportion of large fish (proportional size distribution of LMB > 12 inches was < 33%). These relationships suggest that resource competition among LMB likely contributed to tHg bioaccumulation in reservoirs < 930 acres. Small reservoirs located in northern Missouri also may have greater methylation potential due to warmer water temperatures and anoxic conditions, but more data are needed to confirm these interactions. Fish consumption advisories for reservoirs with large surface area and volume could be reduced from one fish meal per month to one per week. To improve Missouri fisheries and protect consumers, management strategies to limit methylation and improve fish growth should be considered to reduce methylmercury bioaccumulation in small- and medium-sized reservoirs.

Longitudinal study of age of menarche in association with childhood concentrations of persistent organic pollutants.

BACKGROUND: Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study. METHODS: We analyzed data for females enrolled at age 6-8 years in the Breast Cancer and Environment Research Program from California and Ohio. Participants were followed annually 2004-2013 and provided serum (mean age 7.8 years) for measurement of polychlorinated biphenyl (PCB), organochlorine pesticide (OCP), and polybrominated diphenyl ether (PBDE) concentrations. Age of menarche was assigned based on parental and participant reported dates and ages of menarche. Adjusted hazard ratios (aHRs) for menarchal onset were calculated with Cox proportional regression. Body mass index (BMI), potentially on the causal pathway, was added to parallel analyses. RESULTS: Age of menarche was later with higher summed PCB levels (median 11.9 years in quartile 1 [Q1] versus 12.7 in quartile 4 [Q4]) and OCP levels (12.1 years versus 12.4, respectively). When adjusting for all covariates except BMI, higher POP concentrations were associated with later age at menarche (Q4 versus Q1 aHRs: PBDEs 0.75 [95% CI 0.58, 0.97], PCBs 0.67 [95% CI 0.5, 0.89], and OCPs 0.66 [95% CI 0.50, 0.89]). Additional adjustment for BMI attenuated aHRs; PCB aHR approached the null. CONCLUSION: Findings revealed later onset of menarche with higher concentrations of certain POPs, possibly through an association with BMI. Altered pubertal timing may have long lasting effects on reproductive health and disease risk, so continued attention is important for understanding the biological processes affected by hormonally active chemicals.

Age at Pubertal Onset in Girls and Tobacco Smoke Exposure During Pre- and Postnatal Susceptibility Windows.

BACKGROUND: Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and postnatal smoke exposure in relation to timing of early pubertal events. METHODS: An ethnically diverse cohort of 1239 girls was enrolled at age 6-8 years old for a longitudinal study of puberty at three US sites. Girls participated in annual or semi-annual exams to measure anthropometry and Tanner breast and pubic hair stages. Prenatal and current tobacco smoke exposures, as well as covariates, were obtained from parent questionnaire. Cotinine was measured in urine collected at enrollment. Using accelerated failure time models, we calculated adjusted time ratios for age at pubertal onset (maturation stages 2 or higher) and smoke exposure. RESULTS: Girls with higher prenatal (≥5 cigarettes per day) or secondhand smoke exposure had earlier pubic hair development than unexposed (adjusted time ratio: 0.92 [95% CI = 0.87, 0.97] and 0.94 [95% CI = 0.90, 0.97], respectively). Including both exposures in the same model yielded similar associations. Higher urinary cotinine quartiles were associated with younger age at breast and pubic hair onset in unadjusted models, but not after adjustment. CONCLUSIONS: Greater prenatal and childhood secondhand smoke exposure were associated with earlier onset of pubic hair, but not breast, development. These exposures represent modifiable risk factors for early pubertal development that should be considered for addition to the extensive list of adverse effects from tobacco smoke.

Residential proximity to traffic and female pubertal development.

BACKGROUND: Traffic-related air pollution (TRAP) has been linked with several adverse health outcomes, including preterm birth and low birth weight, which are both related to onset of puberty. No studies to date have investigated the association between TRAP and altered pubertal timing. OBJECTIVE: Determine the association between residential proximity to traffic, as a marker of long-term TRAP exposure, and age at pubertal onset in a longitudinal study of girls. METHODS: We analyzed data for 437 girls at the CYGNET study site of the Breast Cancer and Environment Research Program. TRAP exposure was assessed using several measures of residential proximity to traffic based on address at study entry. Using accelerated failure time models, we calculated time ratios (TRs) and their corresponding 95% confidence intervals (CIs) for specified traffic metrics and pubertal onset, defined as stage 2 or higher for breast or pubic hair development (respectively, B2+ and PH2+). Models were adjusted for race/ethnicity, household income, and cotinine levels. RESULTS: At baseline, 71% of girls lived within 150m of a major road. The median age of onset was 10.3years for B2+ and 10.9years for PH2+. Living within 150m downwind of a major road was associated with earlier onset of PH2+ (TR 0.96, 95% CI 0.93, 0.99). Girls in the highest quintile of either distance-weighted traffic density, annual average daily traffic, and/or traffic density also reached PH2+ earlier than girls in the lowest quintiles. CONCLUSIONS: In this first study to assess the association between residential proximity to traffic and pubertal onset we found girls with higher exposure reached one pubertal milestone several months earlier than low exposed girls, even after consideration of likely confounders. Results should be expanded in larger epidemiological studies, and with measured levels of air pollutants.

Thyroid Hormones and Timing of Pubertal Onset in a Longitudinal Cohort of Females, Northern California, 2006-11.

BACKGROUND: Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. METHODS: Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004-11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage ≥2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. RESULTS: At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per µg/dL respectively). CONCLUSIONS: Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche.

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls.

BACKGROUND: Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program. OBJECTIVES: Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset. METHODS: Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1-4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling. RESULTS: Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs. CONCLUSIONS: This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

High exposure of California firefighters to polybrominated diphenyl ethers.

Concern about persistent organic pollutants (POPs) in Californians prompted the state's biomonitoring program to conduct a study in firefighters, who are occupationally exposed to high levels of POPs. In this work we present serum concentrations of several classes of POPs (polybrominated diphenyl ethers [PBDEs], polychlorinated biphenyls [PCBs], and organochlorine pesticides [OCPs]) in 101 Southern California firefighters. Despite recently reported declining trends of PBDEs in Californians, high levels were measured in firefighters' serum (Σ5PBDEs: median = 59.1 ng/(g of lipid); range = 18.8-714 ng/(g of lipid)) in comparison to other populations in California during the same period. In addition, nearly one-third of subjects had particularly high serum levels of decabromodiphenyl ether (BDE-209), consistent with other recent results in firefighters; this pattern may be a marker of recent firefighting activity. In contrast, serum levels of PCBs and OCPs measured in firefighters' sera were not elevated compared to U.S. levels. Multivariable analysis indicated that lower levels of serum PBDEs were associated with turnout gear cleaning and storage practices after fires. Our study supports the hypothesis that firefighting activities are likely to increase exposure to PBDEs and that good housekeeping and personal hygiene practices may reduce exposure to these compounds.