Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry.

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited disease caused by deficient activity of tissue-nonspecific alkaline phosphatase. Many adults with HPP have a high burden of disease, experiencing chronic pain, fatigue, limited mobility, and dental issues, contributing to decreased health-related quality of life (HRQoL). HPP may be treated with the enzyme replacement therapy asfotase alfa though real-world data in adults are limited. This analysis was conducted to assess the clinical effectiveness of asfotase alfa among adults in the Global HPP Registry. METHODS: The Global HPP Registry is an observational, prospective, multinational study. Adults ≥ 18 years of age were included in this analysis if they had serum alkaline phosphatase (ALP) activity below the age- and sex-adjusted reference ranges, and/or ALPL variant(s), and received asfotase alfa for ≥ 6 months. Mobility was assessed with the 6-Minute Walk Test (6MWT), and patient-reported outcomes tools were used to assess pain (Brief Pain Inventory-Short Form), quality of life (36-item Short Form Health Survey, version 2 [SF-36v2]), and disability (Health Assessment Questionnaire-Disability Index) at multiple time points from baseline through Month 36. Data were collected as per usual standard of care; patients may not have contributed data at all time points. RESULTS: A total of 190 patients met the inclusion criteria. For patients with ≥ 1 follow-up measurement, the mean distance achieved on 6MWT increased from 404 m (range 60-632 m) at baseline (n = 31) to 484 m at Month 12 (range 240-739 m; n = 18) and remained above baseline through Month 36 (n = 7). Improvements in mean self-reported pain severity scores ranged from - 0.72 (95% CI: - 1.23, - 0.21; n = 38) to - 1.13 (95% CI: - 1.76, - 0.51; n = 26) and were observed at all time points. Improvements in the Physical Component Summary score of SF-36v2 were achieved by Month 6 and sustained throughout follow-up. There was a trend toward improvement in the Mental Component Summary score of SF-36v2 at most time points, with considerable fluctuations from Months 12 (n = 28) through 36 (n = 21). The most frequent adverse events were injection site reactions. CONCLUSIONS: Adults with HPP who received asfotase alfa for ≥ 6 months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3 years of follow-up. REGISTRATION: NCT02306720; EUPAS13514.

Clinical Profiles of Children with Hypophosphatasia Prior to Treatment with Enzyme Replacement Therapy: An Observational Analysis from the Global HPP Registry.

INTRODUCTION: To better understand the clinical profiles of children with hypophosphatasia (HPP) prior to treatment with enzyme replacement therapy (ERT). METHODS: Pretreatment demographics and medical histories of ERT-treated children (aged < 18 years) enrolled in the Global HPP Registry (2015-2020) were analyzed overall, by age at first HPP manifestation (< 6 months versus 6 months to 18 years) and by geographic region (United States/Canada, Europe, and Japan). RESULTS: Data from 151 children with HPP were analyzed. Sex distribution was balanced overall (52.3% female; 47.7% male) but differed in Japan (63.0% female; 37.0% male). Prior to ERT initiation, common manifestations were skeletal (67.5%) and extraskeletal, with the foremost being muscular (48.3%), constitutional/metabolic (47.0%), and neurologic (39.7%). A high proportion of children who first presented at < 6 months of age (perinatal/infantile period) had a history of bone deformity (59.3%) and respiratory failure (38.3%), while those aged 6 months to 18 years at first manifestation had a predominance of early loss of primary teeth (62.3%) and gross motor delay (41.0%). Japan reported a younger median age overall, the highest proportion of skeletal (80.4%) manifestations and growth impairment, while European data showed the highest proportion of muscular manifestations (70.7%). In the United States/Canada, skeletal and muscular manifestations were reported at the same frequency (57.4%). DISCUSSION/CONCLUSION: Prior to ERT, skeletal and extraskeletal manifestations were commonly reported in children with HPP, with differences by age at first HPP manifestation and geographical region. Comprehensive assessments of children with HPP are warranted prior to ERT initiation.

Growth and disease burden in children with hypophosphatasia.

Objective: Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children. Design: Data from children (aged <18 years) with hypophosphatasia were analyzed from the observational Global Hypophosphatasia Registry. Methods: Anthropometric parameters were evaluated by age group (<2 years and ≥2 years) at assessment. The frequency of hypophosphatasia manifestations was compared between children with short stature (< percentile) and those with normal stature. Results: This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged <2 years and 20.4% of those aged ≥2 years at assessment. Among those with available data (n = 62), height was below the target height (mean: -0.66 standard deviations). Substantial worsening of growth (mean delta height z score: -1.45; delta weight z score: -0.68) occurred before 2 years of age, while in those aged ≥2 years, anthropometric trajectories were maintained (delta height z score: 0.08; delta weight z score: 0.13). Broad-ranging hypophosphatasia manifestations (beyond dental) were observed in most children. Conclusions: Short stature was not a consistent characteristic of children with hypophosphatasia, but growth impairment was observed in those aged <2 years, indicating that hypophosphatasia might affect growth plate activity during infancy. In addition, a broad range of clinical manifestations occurred in those above and below the third percentile for height, suggesting that height alone may not accurately reflect hypophosphatasia disease burden and that weight is less affected than longitudinal growth.

Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry.

BACKGROUND: The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient's symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately. RESULTS: A total of 398 adults with HPP were included; 213 with pediatric-onset (114 treated, 99 untreated) and 141 with adult-onset HPP (2 treated and 139 untreated). The treated, pediatric-onset patients were more likely to have a history of pain (prevalence ratio [PR]: 1.3, 95% confidence interval [CI] 1.1, 1.4), skeletal (PR: 1.3, 95% CI 1.1, 1.6), constitutional/metabolic (PR: 1.7, 95% CI 1.3, 2.0), muscular (PR: 1.8, 95% CI 1.4, 2.1) and neurological (PR: 1.7, 95% CI 1.1, 2.3) manifestations of HPP, and also had poorer measures for health-related quality of life, pain, and disability compared with untreated pediatric-onset patients. In patients with adult-onset HPP, the most frequent signs and symptoms were chronic bone pain (52.5%), dental manifestations (42.6%), fatigue (23.4%), recurrent fractures or pseudofractures (22.0%), and generalized body pain (22.0%). CONCLUSIONS: Along with the more classical skeletal signs and symptoms, pain, muscular, and constitutional/metabolic manifestations are common in adults with HPP, regardless of age of disease onset, highlighting a full spectrum of HPP manifestations.

Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry.

Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non-specific alkaline phosphatase activity. This study aims to assess patient-reported pain, disability and health-related quality of life (HRQoL) in a real-world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient-reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI-SF], Health Assessment Questionnaire Disability Index [HAQ-DI], and 36-Item Short-Form Health Survey version 2 [SF-36v2], respectively) were stratified by pediatric- and adult-onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74% women), 45% had adult-onset HPP and 33% had pediatric-onset HPP (unknown age of onset, 22%). Of those with data, 38% had experienced ≥5 HPP manifestations and 62% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI-SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ-DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF-36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI-SF, HAQ-DI, and SF-36v2 (all p < 0.05). No significant differences between adults with pediatric- and adult-onset HPP were observed for patient-reported outcomes, except for disability and the BPI-SF question "pain at its worst," which were significantly higher among adults with pediatric- versus adult-onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient-reported HRQoL, regardless of age of disease onset. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Posttraumatic Stress Disorder Severity and Insomnia-Related Sleep Disturbances: Longitudinal Associations in a Large, Gender-Balanced Cohort of Combat-Exposed Veterans.

Few studies have investigated the range and severity of insomnia-related sleep complaints among veterans with posttraumatic stress disorder (PTSD), and the temporal association between insomnia and PTSD severity has yet to be examined. To examine these associations, a large, gender-balanced cohort of veterans (N = 1,649) of the Iraq and Afghanistan conflicts participated in longitudinal assessments of PTSD and insomnia-related symptoms over a period of 2.5 years following enrollment (range: 2-4 years). Data were obtained from multiple sources, including interviews, self-report assessments, and electronic medical record data. Three-fourths (74.0%) of veterans with PTSD diagnoses at Time 1 (T1) reported insomnia-related sleep difficulties on at least half the nights during the past 30 days, and one-third of participants had received a prescription for a sedative-hypnotic drug in the past year. Veterans without PTSD had fewer sleep problems overall, although the prevalence of sleep problems was high among all study participants. In longitudinal, cross-lagged panel models, the frequency of sleep problems at T1 independently predicted increases in PTSD severity at Time 2 (T2), B = 0.27, p < .001, after controlling for gender and relevant comorbidities. Conversely, T1 PTSD severity was associated with increasing sleep complaints at T2 but to a lesser degree, B = 0.04, p < .001. Moderately high rates of sedative-hypnotic use were seen in veterans with PTSD, with more frequent use in women compared to men (40.4% vs. 35.0%). Sleep complaints were highly prevalent overall and highlight the need for increased clinical focus on this area.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Gravedad del TEPT y Trastornos del Sueño Relacionados con el Insomnio: Asociaciones Longitudinales en una gran Cohorte, Balanceados por Género. de Veteranos Expuestos al Combate SUEÑO, INSOMNIO Y SEVERIDAD DE TEPT Pocos estudios han investigado el rango y la gravedad de las quejas del sueño relacionadas con el insomnio entre veteranos con trastorno de estrés postraumático (TEPT) y la asociación temporal entre el insomnio y la severidad del TEPT aún no se han examinado. Para examinar estas asociaciones, una gran cohorte de veteranos (N = 1,649) de los conflictos de Irak y Afganistán, balanceados por género, participaron en evaluaciones longitudinales de TEPT y síntomas relacionados con el insomnio durante un período de 2.5 años posteriores a la inscripción (rango: 2-4 años). Los datos se obtuvieron de múltiples fuentes, incluyendo entrevistas, autoevaluaciones y datos de registros médicos electrónicos. Tres cuartos (74.0%) de los veteranos con diagnóstico de TEPT en el tiempo 1 (T1) informaron dificultades de sueño relacionadas con el insomnio en al menos la mitad de las noches durante los últimos 30 días, y un tercio de los participantes habían recibido una prescripción de un fármaco sedante-hipnótico en el último año. Los veteranos sin TEPT tenían menos problemas de sueño en general, aunque la prevalencia de problemas de sueño fue alta entre todos los participantes del estudio. En los modelos longitudinales de panel con retardo cruzado, la frecuencia de los problemas de sueño en T1 predijeron independientemente aumentos en la severidad del TEPT en el Tiempo 2 (T2), B = 0.27, p <.001, después controlar por género y comorbilidades relevantes. Por el contrario, la gravedad del TEPT en T1 se asoció con un aumento de las quejas de sueño en T2 pero en menor grado, B = 0.04, p <.001. Se observaron tasas moderadamente altas de uso de hipnóticos-sedativos en veteranos con TEPT, con un uso más frecuente en mujeres comparadas con hombres (40.4% vs. 35.0%). En general las quejas de sueño fueron altamente prevalentes y destacan la necesidad de una mayor focalización clínica en esta área.

Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry.

BACKGROUND: Hypophosphatasia (HPP) is a rare, systemic disease caused by mutation(s) within the ALPL gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP has a heterogeneous presentation, which coupled with its rarity, often leads to missed/delayed diagnosis and an incomplete understanding of its natural history. To better understand the epidemiology and clinical course of HPP, including timing of diagnosis after first reported manifestation, we present baseline data for patients enrolled in the Global HPP Registry. METHODS: Data were analyzed from patients with an HPP diagnosis confirmed by low serum ALP activity and/or an ALPL pathogenic variant, regardless of prior or current treatment, according to age at enrollment (children: < 18 y; adult: ≥18 y). All analyses were descriptive. RESULTS: Of 269 patients from 11 countries enrolled January 2015-September 2017, 121 (45.0%) were children and 148 (55.0%) were adults. The majority of children and adults were female (61.2 and 73.0%, respectively) and white (57.7 and 90.0%, respectively). Children had a median (min, max) age at earliest reported HPP manifestation of 7.2 months (- 2.3 mo, 16.0 y), which was > 12 months before diagnosis at age 20.4 months (- 0.2 mo, 16.0 y). In adults, the earliest reported manifestation occurred at a median (min, max) age of 37.6 years (0.2 y, 75.2 y), which preceded age at diagnosis (47.5 years [0.2 y, 75.2 y]) by ~ 10 years. Premature loss of deciduous teeth (48.2%, age ≥ 6 mo), bone deformity (32.5%), and failure to thrive (26.7%) were most commonly reported in the HPP-related disease history of children. Pain (74.5%), orthopedic procedures and therapies (44.6%), and recurrent and poorly healing fractures (36.5%) were most commonly reported in the HPP-related disease history of adults. CONCLUSIONS: The Global HPP Registry represents the largest observational study of patients with HPP, capturing real world data. This analysis shows that diagnostic delay is common, reflecting limited awareness of HPP, and that HPP is associated with systemic manifestations across all ages. Many patients diagnosed in adulthood had HPP manifestations in childhood, highlighting the importance of taking thorough medical histories to ensure timely diagnosis. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02306720 , December 2014; ENCePP.eu: EUPAS13526 , May 2016 (retrospectively registered).

Application of linear mixed-effects model with LASSO to identify metal components associated with cardiac autonomic responses among welders: a repeated measures study.

BACKGROUND: Environmental and occupational exposure to metals is ubiquitous worldwide, and understanding the hazardous metal components in this complex mixture is essential for environmental and occupational regulations. OBJECTIVE: To identify hazardous components from metal mixtures that are associated with alterations in cardiac autonomic responses. METHODS: Urinary concentrations of 16 types of metals were examined and 'acceleration capacity' (AC) and 'deceleration capacity' (DC), indicators of cardiac autonomic effects, were quantified from ECG recordings among 54 welders. We fitted linear mixed-effects models with least absolute shrinkage and selection operator (LASSO) to identify metal components that are associated with AC and DC. The Bayesian Information Criterion was used as the criterion for model selection procedures. RESULTS: Mercury and chromium were selected for DC analysis, whereas mercury, chromium and manganese were selected for AC analysis through the LASSO approach. When we fitted the linear mixed-effects models with 'selected' metal components only, the effect of mercury remained significant. Every 1 µg/L increase in urinary mercury was associated with -0.58 ms (-1.03, -0.13) changes in DC and 0.67 ms (0.25, 1.10) changes in AC. CONCLUSION: Our study suggests that exposure to several metals is associated with impaired cardiac autonomic functions. Our findings should be replicated in future studies with larger sample sizes.

Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia.

BACKGROUND: Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited. PATIENTS AND METHODS: We conducted a cohort study with nested case-control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age ≥40 years and at least 3 years after the start of their electronic medical record. We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated. RESULTS: Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05-4.14) and case-control analyses (OR=3.31, 95% CI 2.66-4.10), whereas the risk was null for users of AB only. The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia. The risk was higher for dutasteride than for finasteride. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61-3.80). CONCLUSION: In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure.

An epigenome-wide association analysis of cardiac autonomic responses among a population of welders.

DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.

Association of air particulate pollution with bone loss over time and bone fracture risk: analysis of data from two independent studies.

BACKGROUND: Air particulate matter (PM) is a ubiquitous environmental exposure associated with oxidation, inflammation, and age-related chronic disease. Whether PM is associated with loss of bone mineral density (BMD) and risk of bone fractures is undetermined. METHODS: We conducted two complementary studies of: (i) long-term PM <2.5 µm (PM2.5) levels and osteoporosis-related fracture hospital admissions among 9.2 million Medicare enrollees of the Northeast/Mid-Atlantic United States between 2003-2010; (ii) long-term black carbon [BC] and PM2.5 levels, serum calcium homeostasis biomarkers (parathyroid hormone, calcium, and 25-hydroxyvitamin D), and annualized BMD reduction over a 8-year follow-up of 692 middle-aged (46.7±12.3 yrs), low-income BACH/Bone cohort participants. FINDINGS: In the Medicare analysis, risk of bone fracture admissions at osteoporosis-related sites was greater in areas with higher PM2.5 levels (Risk ratio [RR] 1.041, 95% Confidence Interval [CI], 1.030, 1.051). This risk was particularly high among low-income communities (RR 1.076; 95% CI, 1.052, 1.100). In the longitudinal BACH/Bone study, baseline BC and PM2.5 levels were associated with lower serum PTH (Estimate for baseline one interquartile increase in 1-year average BC= -1.16, 95% CI -1.93, -0.38; Estimate for baseline one interquartile increase in 1-year average PM2.5= -7.39; 95%CI -14.17, -0.61). BC level was associated with higher BMD loss over time at multiple anatomical sites, including femoral neck (-0.08%/year per one interquartile increase; 95% CI -0.14, -0.02%/year) and ultradistal radius (-0.06%/year per one interquartile increase; 95% CI -0.12, -0.01%/year). INTERPRETATION: Our results suggest that poor air quality is a modifiable risk factor for bone fractures and osteoporosis, especially in low-income communities.

Validity of Self-Reported Tobacco Smoke Exposure among Non-Smoking Adult Public Housing Residents.

INTRODUCTION: Tobacco smoke exposure (TSE) in public multi-unit housing (MUH) is of concern. However, the validity of self-reports for determining TSE among non-smoking residents in such housing is unclear. METHODS: We analyzed data from 285 non-smoking public MUH residents living in non-smoking households in the Boston area. Participants were interviewed about personal TSE in various locations in the past 7 days and completed a diary of home TSE for 7 days. Self-reported TSE was validated against measurable saliva cotinine (lower limit of detection (LOD) 0.02 ng/ml) and airborne apartment nicotine (LOD 5 ng). Correlations, estimates of inter-measure agreement, and logistic regression assessed associations between self-reported TSE items and measurable cotinine and nicotine. RESULTS: Cotinine and nicotine levels were low in this sample (median = 0.026 ng/ml and 0.022 µg/m(3), respectively). Prevalence of detectable personal TSE was 66.3% via self-report and 57.0% via measurable cotinine (median concentration among those with cotinine>LOD: 0.057 ng/ml), with poor agreement (kappa = 0.06; sensitivity = 68.9%; specificity = 37.1%). TSE in the home, car, and other peoples' homes was weakly associated with cotinine levels (Spearman correlations rs = 0.15-0.25), while TSE in public places was not associated with cotinine. Among those with airborne nicotine and daily diary data (n = 161), a smaller proportion had household TSE via self-report (41.6%) compared with measurable airborne nicotine (53.4%) (median concentration among those with nicotine>LOD: 0.04 µg/m(3)) (kappa = 0.09, sensitivity = 46.5%, specificity = 62.7%). CONCLUSIONS: Self-report alone was not adequate to identify individuals with TSE, as 31% with measurable cotinine and 53% with measurable nicotine did not report TSE. Self-report of TSE in private indoor spaces outside the home was most associated with measurable cotinine in this low-income non-smoking population.

Sexual Health in Male and Female Iraq and Afghanistan U. S. War Veterans With and Without PTSD: Findings From the VALOR Cohort.

We sought to determine whether posttraumatic stress disorder (PTSD) was associated with sexual health in returned warzone-deployed veterans from the recent Iraq and Afghanistan conflicts. We studied 1,581 males and females from the Veterans After-Discharge Longitudinal Registry, a gender-balanced U.S. Department of Veterans Affairs registry of health care-seeking veterans with and without PTSD. Approximately one quarter (25.1%) of males (n = 198) and 12.7% of females (n = 101) had a sexual dysfunction diagnosis and/or prescription treatment for sexual dysfunction. Both genders were more likely to have a sexual dysfunction diagnosis and/or prescription treatment if they had PTSD compared with those without PTSD (male: 27.3% vs. 21.1%, p = .054; female: 14.9% vs. 9.4%, p = .022). Among the 1,557 subjects analyzed here, males with PTSD had similar levels of sexual activity compared to those without PTSD (71.2% vs. 75.4%, p = .22), whereas females with PTSD were less likely to be sexually active compared to females without PTSD (58.7% vs. 72.1%, p < .001). Participants with PTSD were also less likely to report sex-life satisfaction (male: 27.6% vs. 46.0%, p < .001; female: 23.0% vs. 45.7%, p < .001) compared with those without PTSD. Although PTSD was not associated with sexual dysfunction after adjusting for confounding factors, it was significantly negatively associated with sex-life satisfaction in female veterans with a prevalence ratio of .71, 95% confidence interval [.57, .90].

Environmental and occupational particulate matter exposures and ectopic heart beats in welders.

OBJECTIVES: Links between arrhythmias and particulate matter exposures have been found among sensitive populations. We examined the relationship between personal particulate matter ≤2.5 µm aerodynamic diameter (PM2.5) exposures and ectopy in a panel study of healthy welders. METHODS: Simultaneous ambulatory ECG and personal PM2.5 exposure monitoring with DustTrak Aerosol Monitor was performed on 72 males during work and non-work periods for 5-90 h (median 40 h). ECGs were summarised hourly for supraventricular ectopy (SVE) and ventricular ectopy (VE). PM2.5 exposures both work and non-work periods were averaged hourly with lags from 0 to 7 h. Generalised linear mixed-effects models with a random participant intercept were used to examine the relationship between PM2.5 exposure and the odds of SVE or VE. Sensitivity analyses were performed to assess whether relationships differed by work period and among current smokers. RESULTS: Participants had a mean (SD) age of 38 (11) years and were monitored over 2993 person-hours. The number of hourly ectopic events was highly skewed with mean (SD) of 14 (69) VE and 1 (4) SVE. We found marginally significant increases in VE with PM2.5 exposures in the sixth and seventh hour lags, yet no association with SVE. For every 100 µg/m(3) increase in sixth hour lagged PM2.5, the adjusted OR (95% CI) for VE was 1.03 (1.00 to 1.05). Results persisted in work or non-work exposure periods and non-smokers had increased odds of VE associated with PM2.5 as compared with smokers. CONCLUSIONS: A small increase in the odds of VE with short-term PM2.5 exposure was observed among relatively healthy men with environmental and occupational exposures.

Long-Term Metal PM2.5 Exposures Decrease Cardiac Acceleration and Deceleration Capacities in Welders.

OBJECTIVE: The aim of the study was to clarify whether long-term metal particulates affect cardiac acceleration capacity (AC), deceleration capacity (DC), or both. METHODS: We calculated chronic exposure index (CEI) for PM2.5 over the work life of 50 boilermakers and obtained their resting AC and DC. Linear regression was used to assess the associations between CEI PM2.5 exposure and each of AC and DC, controlling for age, acute effects of welding exposure, and diurnal variation. RESULTS: Mean (standard deviation) CEI for PM2.5 exposure was 1.6 (2.4) mg/m-work years and ranged from 0.001 to 14.6 mg/m-work years. In our fully adjusted models, a 1 mg/m-work year increase in CEI for PM2.5 was associated with a decrease of 1.03 (95% confidence interval: 0.10, 1.96) ms resting AC, and a decrease of 0.67 (95% confidence interval: -0.14, 1.49) ms resting DC. CONCLUSIONS: Long-term metal particulate exposures decrease cardiac accelerations and decelerations.

Are the Associations of Cardiac Acceleration and Deceleration Capacities With Fine Metal Particulate in Welders Mediated by Inflammation?

OBJECTIVE: The aim of this study was to investigate whether associations of acceleration capacity (AC) and deceleration capacity (DC) with metal-PM2.5 are mediated by inflammation. METHODS: We obtained PM2.5, C-reactive protein, interleukin (IL)-6, 8, and 10, and electrocardiograms to compute AC and DC, from 45 male welders. Mediation analyses were performed using linear mixed models to assess associations between PM2.5 exposure, inflammatory mediator, and AC or DC, controlling for covariates. RESULTS: The proportion of total effect of PM2.5 on AC or DC (indirect effect) mediated through IL-6 on AC was 4% at most. Controlling for IL-6 (direct effect), a 1 mg/m increase of PM2.5 was associated with a decrease of 2.16 (95% confidence interval -0.36 to 4.69) msec in AC and a decrease of 2.51 (95% confidence interval -0.90 to 5.93) msec in DC. CONCLUSION: IL-6 may be mediating the effect of metal particulates on AC.

Effects of Personal Exposure to Ambient Fine Particulate Matter on Acute Change in Nocturnal Heart Rate Variability in Subjects Without Overt Heart Disease.

The immediate effect within minutes to hours of personal exposure to ambient fine particulate matter (PM2.5) on cardiac autonomic function is limited, particularly at night. Our study aimed to assess the lagged association between personal exposure to PM2.5 and nocturnal heart rate variability. Repeated measures panel study among 21 community adults recruited from a local health clinic during the period of March 1, 2004, to August 31, 2004, in Boston, Massachusetts, in the United States. Ambulatory electrocardiogram and continuous monitoring of personal exposure to PM2.5 and were measured for up to 2 consecutive days. We calculated 5-minute time-specific average PM2.5 exposure for each participant. Mixed-effects models were fit for 5-minute SD of normal-to-normal intervals (SDNN) and 5-minute heart rate in relation to 5-minute PM2.5 exposure lagged in 5-minute intervals up to 4 hours. We found an 8.4% decrease in nocturnal SDNN (95% confidence interval [CI] -11.3% to -5.5%) and a 1.9% increase in nighttime heart rate (95% CI 1.1% to 2.7%) for an interquartile range increase in PM2.5 (13.6 µg/m(3)), after adjusting for confounders. Significant decreases in nocturnal SDNN associated with PM2.5 exposure occurred within 2.5 hours. The largest decrease in nocturnal SDNN of -12.8% (95% CI -16.4 to -9.1%) that was associated with PM2.5 exposure was found with a lag of 25 minutes. Rapid changes in nocturnal heart rate variability associated with personal PM2.5 exposure occurred within the previous 2.5 hours, with the largest effects at 25 minutes, suggesting immediate cardiac autonomic effects of fine particulate exposure.

Assessment of Residents' Attitudes and Satisfaction Before and After Implementation of a Smoke-Free Policy in Boston Multiunit Housing.

INTRODUCTION: In 2012, the Boston Housing Authority (BHA) in Massachusetts implemented a smoke-free policy prohibiting smoking within its residences. We sought to characterize BHA resident experiences before and after the smoke-free policy implementation, and compare them to that of nearby residents of the Cambridge Housing Authority, which had no such policy. METHODS: We recruited a convenience sample of nonsmoking residents from the BHA and Cambridge Housing Authority. We measured residents' awareness and support of their local smoking policies before and 9-12 months after the BHA's policy implementation, as well as BHA respondents' attitudes towards the smoke-free policy. We assessed tobacco smoke exposure via saliva cotinine, airborne apartment nicotine, and self-reported number of days smelling smoke in the home. We evaluated predictors of general satisfaction at follow-up using linear regression. RESULTS: At follow-up, 91% of BHA respondents knew that smoking was not allowed in apartments and 82% were supportive of such a policy in their building. BHA residents believed enforcement of the smoke-free policy was low. Fifty-one percent of BHA respondents indicated that other residents "never" or "rarely" followed the new smoke-free rule and 41% of respondents were dissatisfied with policy enforcement. Dissatisfaction with enforcement was the strongest predictor of general housing satisfaction, while objective and self-reported measures of tobacco smoke exposure were not predictive of satisfaction. At follow-up, 24% of BHA participants had complained to someone in charge about policy violations. CONCLUSIONS: Resident support for smoke-free policies is high. However, lack of enforcement of smoke-free policies may cause frustration and resentment among residents, potentially leading to a decrease in housing satisfaction. IMPLICATIONS: Smoke-free housing laws are becoming increasingly prevalent, yet little is known about satisfaction and compliance with such policies post-implementation. We evaluated nonsmoking residents' attitudes about smoke-free rules and their satisfaction with enforcement 1 year after the BHA implemented its comprehensive smoke-free policy. We found that while residents were supportive of the policy, they believed enforcement was low, a perception that was associated with a drop in housing satisfaction. Our findings point to a desire for smoke-free housing among public housing residents, and the importance of establishing systems and guidelines to help landlords monitor and enforce these policies effectively.

Short-term metal particulate exposures decrease cardiac acceleration and deceleration capacities in welders: a repeated-measures panel study.

OBJECTIVE: Acceleration (AC) and deceleration (DC) capacities measure heart rate variability during speeding up and slowing down of the heart, respectively. We investigated associations between AC and DC with occupational short-term metal PM2.5 exposures. METHODS: A panel of 48 male welders had particulate matter less than 2.5 microns in diameter (PM2.5) exposure measurements over 4-6 h repeated over 5 sampling periods between January 2010 and June 2012. We simultaneously obtained continuous recordings of digital ECG using a Holter monitor. We analysed ECG data in the time domain to obtain hourly AC and DC. Linear mixed models were used to assess the associations between hourly PM2.5 exposure and each of hourly AC and DC, controlling for age, smoking status, active smoking, exposure to secondhand smoke, season/time of day when ECG reading was obtained and baseline AC or DC. We also ran lagged exposure response models for each successive hour up to 3 h after onset of exposure. RESULTS: Mean (SD) shift PM2.5 exposure during welding was 0.47 (0.43) mg/m(3). Significant exposure-response associations were found for AC and DC with increased PM2.5 exposure. In our adjusted models without any lag between exposure and response, a 1 mg/m(3) increase of PM2.5 was associated with a decrease of 1.46 (95% CI 1.00 to 1.92) ms in AC and a decrease of 1.00 (95% CI 0.53 to 1.46) ms in DC. The effect of PM2.5 on AC and DC was maximal immediately postexposure and lasted 1 h following exposure. CONCLUSIONS: There are short-term effects of metal particulates on AC and DC.

Changes in Tobacco Smoke Exposure following the Institution of a Smoke-Free Policy in the Boston Housing Authority.

INTRODUCTION: To protect residents from tobacco smoke exposure (TSE), the Boston Housing Authority (BHA) prohibited smoking in BHA-owned apartments beginning in 2012. Our goal was to determine if the smoke-free policy reduced TSE for non-smoking BHA residents. METHODS: We compared TSE before the smoke-free policy (2012) and one year later among BHA residents as well as residents of the neighboring Cambridge Housing Authority (CHA) where no such policy was in place. Participants were a convenience sample of adult non-smoking BHA and CHA residents cohabitating with only non-smokers. Main outcomes were 7-day airborne nicotine in participants' apartments; residents' saliva cotinine; and residents' self-reported TSE. RESULTS: We enrolled 287 confirmed non-smokers (192 BHA, 95 CHA). Seventy-nine percent (229) were assessed at follow-up. At baseline, apartment and resident TSE were high in both housing authorities (detectable airborne nicotine: 46% BHA, 48% CHA; detectable saliva cotinine: 49% BHA, 70% CHA). At follow-up there were significant but similar declines in nicotine in both sites (detectable: -33% BHA, -39% CHA, p = 0.40). Detectable cotinine rose among BHA residents while declining among CHA participants (+17% BHA vs. -13% CHA, p = 0.002). Resident self-reported TSE within and outside of the housing environment decreased similarly for both BHA and CHA residents. CONCLUSIONS: Apartment air nicotine decreased after the introduction of the smoke-free policy, though the decline may not have resulted from the policy. The BHA policy did not result in reduced individual-level TSE. Unmeasured sources of non-residential TSE may have contributed to BHA residents' cotinine levels.