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OBJECTIVE: Infancy is both a critical window for hypothalamic-pituitary-adrenal (HPA) axis development, and a sensitive period for social-emotional influences. We hypothesized that the social-emotional quality of maternal-infant interactions are associated with methylation of HPA-axis gene NR3C1 later in childhood. METHODS: Using a subsample of 114 mother-infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven selected CpG sites from NR3C1 in whole blood at age 7 years, including the main predictor variable of the first principal component score of observed maternal-infant interaction quality (derived from the Thorpe Interaction Measure at 12 months of age) and covariates of cell-type proportion, maternal financial difficulties and marital status at 8 months postnatal, child birthweight, and sex. RESULTS: CpG site cg27122725 methylation was negatively associated with warmer, more positive maternal interaction with her infant (ß = 0.19, p = .02, q = 0.13). In sensitivity analyses, the second highest quartile of maternal behavior (neutral, hesitant behavior) was positively associated with cg12466613 methylation. The other five CpG sites were not significantly associated with maternal-infant interaction quality. CONCLUSIONS: Narrow individual variation of maternal interaction with her infant is associated with childhood methylation of two CpG sites on NR3C1 that may be particularly sensitive to environmental influences. Infancy may be a sensitive period for even small influences from the social-emotional environment on the epigenetic determinants of HPA-axis function.
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Metilação de DNA , Relações Mãe-Filho , Mães , Criança , Feminino , Humanos , Lactente , Sistema Hipotálamo-Hipofisário , Estudos Longitudinais , Mães/psicologia , Receptores de Glucocorticoides/genética , Ilhas de CpG/genéticaRESUMO
OBJECTIVES: Stressful experiences may initiate developmentally plastic responses toward a faster reproductive strategy. This study tests whether adverse childhood experiences (ACEs) are associated with characteristics of faster reproductive strategies: earlier menarche and reduced prenatal investment in offspring in a well-nourished, low-immune system burden population. MATERIALS AND METHODS: We analyzed the first 214 enrollees of the prenatal-birth Albany Infant and Mother Study. Mother's menarcheal age, offspring gestational age at birth, and cephalization index (head circumference/weight, cm/g) were derived from medical records. Linear regression models tested the contribution of self-reported ACEs from 0 to 18 years of age to menarcheal age and the contribution of menarcheal age to offspring gestational age and cephalization index. Birth outcome models included covariates self-reported maternal race, education, prenatal smoking, prenatal diet, newborn sex, parity, delivery method, and labor induction derived from medical records. RESULTS: More ACEs were associated with earlier age at menarche, controlling for covariates (ß = -.18, SE = 0.048, p < .001), though timing of ACEs relative to menarche is unknown. Earlier menarcheal age was associated with offspring higher cephalization index (ß = -.01, SE = 0.006, p < .05). Stratified models showed a significant relationship in high (≥2) ACEs group (ß = -.02, SE = 0.009, p < .05), not present among low ACEs. Menarcheal age predicted gestational age only among those with high ACEs (ß = .22, SE = 0.091, p < .05). DISCUSSION: In a well-nourished population, early life stress can result in faster reproductive strategies, initiating sexual maturation earlier, and reducing prenatal investment in individual offspring. Early age at menarche following childhood stress has a stronger relationship with adverse birth outcomes than early menarche without exposure to adverse childhood stress.
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Experiências Adversas da Infância , Idade Gestacional , Menarca , Estresse Psicológico/etiologia , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , New York , Adulto JovemRESUMO
Introduction Adverse childhood experiences (ACEs) can deleteriously affect health, including pregnancy and birth outcomes occurring later in life. Identification of modifiable factors during pregnancy that buffer the ill effects of adversity is warranted. Social support during pregnancy can promote better birth outcomes, yet it is unknown whether it could also mitigate perinatal risks stemming from ACEs. Thus, this study considers multiple forms of social support in pregnancy as modifiers of an ACEs and fetal growth association. Methods Data were collected from mother and infant pairs from an ongoing prospective birth cohort. Women enrolled around 27 weeks gestation and completed gold-standard assessments of ACEs and social support. Infant cephalization index scores [(head circumference /birthweight) × 100; a marker of asymmetric fetal growth] were derived. Multivariable regression models tested main effects and interaction between ACEs and social support in relation to infant cephalization. Results Higher levels of ACEs were associated with higher cephalization scores (ß = 0.01, SE = 0.01, p < 0.05) whereas higher social support was associated with lower cephalization scores (ß = - 0.03, SE = 0.01, p < 0.05). A significant interaction was observed showing a protective effect of social support among those with low (0 events) and moderate (1-3 events) ACEs but not among those with high ACEs (4 + events; p < 0.05). Tangible and emotional support, but not information support, contributed to the associations. Discussion Maternal ACEs can deleteriously affect birth size, yet social support during pregnancy provides some buffer from its enduring effects. Interventions designed to enhance pregnancy social support may not only improve maternal wellbeing, but may also safeguard infant health.
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Experiências Adversas da Infância/métodos , Mães/psicologia , Apoio Social , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Humanos , New York , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: The aim of this research is to identify whether specific aspects of the early life psychosocial environment such as quality of home and maternal-infant interaction are associated with increased infant adiposity, in a disadvantaged population in the United States. METHODS: Data on 121 mother-infant pairs from the Albany Pregnancy and Infancy Lead Study were analyzed using three multiple linear regression models with subscapular skinfold thickness (SST), triceps skinfold thickness (TST), and weight z-scores at 12 months of age as outcome variables. Maternal-infant interaction was indexed by the Nursing Child Assessment Teaching Scales (NCATS) and home environment quality was indexed by the Home Observation for Measurement of the Environment (HOME). RESULTS: In models including infant birth weight, cigarette use in second trimester, infant caloric intake at 9-12 months, size at birth for gestational age, infant sex, and mother's prepregnancy BMI, specific subscales of NCATs predicted infant adiposity z-scores. Poorer mother's response to infant distress was associated with greater SST ( ß = -0.20, P = .02), TST ( ß = -0.19, P = .04), and weight ( ß = -0.14, P = .05). Better maternal sensitivity to infant cues was associated with larger SST ( ß = 0.25, P < .01), while mother's poorer social-emotional growth fostering predicted greater SST ( ß = -0.23, P < .01) and weight ( ß = -0.16, P = .03). Better scores on HOME Organization of the Environment were associated with greater SST ( ß = 0.34, P = .02) and TST ( ß = 0.33, P = .04). CONCLUSIONS: Emotionally relevant aspects of the maternal-infant interaction predicted infant adiposity, though in different directions. This indicates that the psychosocial environment, through maternal behavior, may influence infant adiposity. However, the general home environment was not consistently related to infant adiposity.
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Adiposidade , Peso Corporal , Relações Mãe-Filho , Fatores Socioeconômicos , Adolescente , Adulto , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , New York , Meio Social , Adulto JovemRESUMO
PURPOSE: To examine the relationships among health literacy, risk perceptions, COVID-19 information overload, health information seeking, and race/ethnicity. DESIGN: A cross-sectional non-probability community survey conducted between December 2020 and January 2021. A questionnaire was developed in collaboration with a local minority health task force. SETTING: Albany, New York, USA. SAMPLE: 331 adults residing in Albany, NY and neighboring areas (80.3% completion rate). MEASURES: Multi-item scales were used to measure health literacy, perceived severity, perceived susceptibility, information overload, and health information seeking frequency and types. ANALYSIS: We conducted multivariate regression analysis. RESULTS: Health literacy (standardized ß = -.33, P < .001) and perceived severity (ß = -.23, P < .001) were negatively associated with information overload. Information overload was negatively associated with health information seeking frequency (ß = -.16, P < .05) and types (ß = -.19, P < .01). A further analysis shows several factors, including information overload and race (African Americans), were negatively related to seeking specific types of information. CONCLUSION: We find that low health literacy and perceived severity contribute to information overload and that information overload adversely affects health information seeking. Black individuals are less likely to search for certain types of information. The cross-sectional study design limits our ability to determine causality. Future research should employ panel data to determine the directionality of the observed relationships.
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COVID-19 , Letramento em Saúde , Adulto , Humanos , Estudos Transversais , Comportamento de Busca de Informação , Inquéritos e QuestionáriosRESUMO
Cannabis use has increased sharply in the last 20 y among adults, including reproductive-aged women. Its recent widespread legalization is associated with a decrease in risk perception of cannabis use during breastfeeding. However, the effect of cannabis use (if any) on milk production and milk composition is not known. This narrative review summarizes current knowledge related to maternal cannabis use during breastfeeding and provides an overview of possible pathways whereby cannabis might affect milk composition and production. Several studies have demonstrated that cannabinoids and their metabolites are detectable in human milk produced by mothers who use cannabis. Due to their physicochemical properties, cannabinoids are stored in adipose tissue, can easily reach the mammary gland, and can be secreted in milk. Moreover, cannabinoid receptors are present in adipocytes and mammary epithelial cells. The activation of these receptors directly modulates fatty acid metabolism, potentially causing changes in milk fatty acid profiles. Additionally, the endocannabinoid system is intimately connected to the endocrine system. As such, it is probable that interactions of exogenous cannabinoids with the endocannabinoid system might modify release of critical hormones (e.g., prolactin and dopamine) that regulate milk production and secretion. Nonetheless, few studies have investigated effects of cannabis use (including on milk production and composition) in lactating women. Additional research utilizing robust methodologies are needed to elucidate whether and how cannabis use affects human milk production and composition.
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Canabinoides , Cannabis , Adulto , Feminino , Humanos , Animais , Lactação , Leite Humano/química , Aleitamento Materno , Endocanabinoides/análise , Endocanabinoides/metabolismo , Endocanabinoides/farmacologia , Leite/química , Canabinoides/farmacologia , Canabinoides/análise , Canabinoides/metabolismo , Ácidos Graxos/farmacologiaRESUMO
Background and Objectives: As cannabis use increases among reproductive-aged women, there is a growing need to better understand the presence of cannabinoids in milk produced by women using cannabis. It is unclear how concentrations of cannabinoids such as delta-9-tetrahydrocannabinol (Δ9-THC) persist in milk after cannabis use and what factors contribute to variation in milk Δ9-THC concentrations. Our objectives were to measure cannabinoids in human milk following cannabis abstention, after single and repeated instances of cannabis use, and identify factors contributing to concentration variation. Methods: The Lactation and Cannabis (LAC) Study prospectively observed 20 breastfeeding participants who frequently used cannabis (≥1/week), had enrolled <6 months postpartum, were feeding their infant their milk ≥5 times/day, and were not using any illicit drugs. Participants collected a baseline milk sample after ≥12 hours of abstaining from cannabis and five milk samples at set intervals over 8-12 hours after initial cannabis use. Participants completed surveys and recorded self-directed cannabis use during the study period. Results: Δ9-THC peaked 120 minutes after a single instance of cannabis use (median, n = 9). More instances of cannabis use during the study period were associated with greater Δ9-THC area-under-the-curve concentrations (ρ = 0.65, p = 0.002), indicating Δ9-THC bioaccumulation in most participants. Baseline Δ9-THC logged concentration was positively associated with self-reported frequency of cannabis use (b = 0.57, p = 0.01). Conclusions: Cannabinoids are measurable in human milk following cannabis use, and concentrations remain elevated with repeated cannabis use over a day. Substantial variation in Δ9-THC milk concentrations reflects individual differences in characteristics and behavior, including average postpartum frequency of cannabis use.
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Aleitamento Materno , Dronabinol , Lactação , Leite Humano , Humanos , Feminino , Leite Humano/química , Adulto , Estudos Prospectivos , Dronabinol/análise , Canabinoides/análise , Cannabis/química , Recém-Nascido , Adulto Jovem , Lactente , Período Pós-PartoRESUMO
OBJECTIVE: Our primary objective was to understand breastfeeding individuals' decisions to use cannabis. Specifically, we investigated reasons for cannabis use, experiences with healthcare providers regarding use, and potential concerns about cannabis use. METHODS: We collected survey data from twenty breastfeeding participants from Washington and Oregon who used cannabis at least once weekly. We documented individuals' cannabis use and analyzed factors associated with their decisions to use cannabis during lactation. Qualitative description was used to assess responses to an open-ended question about potential concerns. RESULTS: Fifty-five percent of participants (n = 11) reported using cannabis to treat or manage health conditions, mostly related to mental health. Eighty percent of participants (n = 16) reported very few or no concerns about using cannabis while breastfeeding, although participants who used cannabis for medical purposes had significantly more concerns. Most participants (n = 18, 90%) reported receiving either no or unhelpful advice from healthcare providers. Four themes arose through qualitative analysis, indicating that breastfeeding individuals are: 1) identifying research gaps and collecting evidence; 2) monitoring their child's health and development; 3) monitoring and titrating their cannabis use; and 4) comparing risks between cannabis and other controlled substances. CONCLUSIONS: Breastfeeding individuals reported cannabis for medical and non-medical reasons and few had concerns about cannabis use during breastfeeding. Breastfeeding individuals reported using a variety of strategies and resources in their assessment of risk or lack thereof when deciding to use cannabis. Most participants reported receiving no helpful guidance from healthcare providers.
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The human milk microbiome (HMM) is hypothesized to be seeded by multiple factors, including the infant oral microbiome during breastfeeding. However, it is not known whether breastfeeding patterns (e.g., frequency or total time) impact the composition of the HMM. As part of the Mother-Infant Microbiomes, Behavior, and Ecology Study (MIMBES), we analyzed data from naturalistic observations of 46 mother-infant dyads living in the US Pacific Northwest and analyzed milk produced by the mothers for its bacterial diversity and composition. DNA was extracted from milk and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. We hypothesized that number of breastfeeding bouts (breastfeeding sessions separated by >30 seconds) and total time breastfeeding would be associated with HMM α-diversity (richness, diversity, or evenness) and differential abundance of HMM bacterial genera. Multiple linear regression was used to examine associations between HMM α-diversity and the number of breastfeeding bouts or total time breastfeeding and selected covariates (infant age, maternal work outside the home, frequency of allomother physical contact with the infant, non-household caregiving network). HMM richness was inversely associated with number of breastfeeding bouts and frequency of allomother physical contact, but not total time breastfeeding. Infants' non-household caregiving network was positively associated with HMM evenness. In two ANCOM-BC analyses, abundances of 5 of the 35 most abundant genera were differentially associated with frequency of breastfeeding bouts (Bifidobacterium, Micrococcus, Pedobacter, Acidocella, Achromobacter); 5 genera (Bifidobacterium, Agreia, Pedobacter, Rugamonas, Stenotrophomonas) were associated with total time breastfeeding. These results indicate that breastfeeding patterns and infant caregiving ecology may play a role in influencing HMM composition. Future research is needed to identify whether these relationships are consistent in other populations and if they are associated with variation in the infant's gastrointestinal (including oral) microbiome.
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Microbiota , Leite Humano , Feminino , Humanos , Lactente , Leite Humano/microbiologia , Aleitamento Materno , Mães , RNA Ribossômico 16S/genética , Microbiota/genética , Bactérias/genéticaRESUMO
OBJECTIVE: To describe psoriatic arthritis (PsA) flares and their effect on patient-reported outcomes (PROs). METHODS: Cross-sectional surveys of rheumatologists/dermatologists and their patients with PsA were conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States, capturing data on physician-reported patient flare status, demographics, PsA severity, and clinical outcomes. Patient-completed surveys captured data on PROs: 5-level EuroQol 5-dimension, Work Productivity and Activity Impairment questionnaire, Health Assessment Questionnaire-Disability Index, and 12-item Psoriatic Arthritis Impact of Disease questionnaire. Patients were compared by flare status using parametric and nonparametric tests. Multivariate regression was used to identify flare associations. Multivariate logistic regression adjusted for patient demographics and physician specialty assessed the effect of flare status. RESULTS: Among 2238 patients (586 from the US, 1652 from Europe) managed by 572 physicians, physician-reported flare was present for 168 patients (7.5%), and self-reported flare was present for 95 patients (10% of available data). Mean (SD) flare count over 12 months was 2.2 (4.9), lasting on average 16.4 (16.2) days. Flare status was linked to worse PROs. Patients who had not flared in the last 12 months or had never flared had a higher quality of life, lower overall work impairment, and a lower degree of disability compared with patients who were currently experiencing a flare (all; P < 0.01). CONCLUSION: Actively experiencing a flare adversely affected QOL, disability, and work productivity. PsA flares should be routinely assessed and managed in clinical care.
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Artrite Psoriásica , Médicos , Humanos , Estados Unidos , Qualidade de Vida , Estudos Transversais , Inquéritos e Questionários , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Although psoriatic arthritis (PsA) is equally present in men and women, sex may influence clinical manifestations and the impact of disease on patients' lives. This study assessed differences in clinical characteristics, disability, quality of life (QOL), and work productivity by sex in real-world practice. METHODS: A cross-sectional survey of rheumatologists/dermatologists and their patients with PsA was conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States between June and August 2018. Data collected included demographics, treatment use, clinical characteristics (tender joint count, swollen joint count, body surface area affected by psoriasis), QOL (EuroQoL 5-Dimension questionnaire [EQ-5D], Psoriatic Arthritis Impact of Disease [PsAID12]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and work productivity (Work Productivity and Impairment Index [WPAI]). Outcomes were compared between men and women using parametric and nonparametric tests, as appropriate. RESULTS: Of 2270 patients (mean age 48.6 [SD 13.3] yrs, mean disease duration 4.9 [SD 6.0] yrs), 1047 (46.1%) were women. Disease duration, disease presentation, and biologic use (mean 54.2%) were comparable between women and men. Women reported worse QOL (EQ-5D: 0.80 [SD 0.2] vs 0.82 [SD 0.2]; P = 0.02), greater disability (HAQ-DI: 0.56 [SD 0.6] vs 0.41 [SD 0.5]; P < 0.01) and work activity impairment (WPAI: 27.9% [SD 22.0] vs 24.6% [SD 22.4]; P < 0.01) than men. However, women had a lower burden of comorbidities (Charlson Comorbidity Index: 1.10 [SD 0.5] vs 1.15 [SD 0.6]; P < 0.01). CONCLUSION: In patients with similar PsA disease activity and treatment, women experienced greater disease impact than men. This represents a significant consideration for the therapeutic management of PsA.
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Artrite Psoriásica , Masculino , Humanos , Feminino , Estados Unidos , Pessoa de Meia-Idade , Artrite Psoriásica/tratamento farmacológico , Qualidade de Vida , Estudos Transversais , Europa (Continente) , Efeitos Psicossociais da Doença , Inquéritos e Questionários , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To determine the individual impact of key manifestations of psoriatic arthritis (PsA) on quality of life (QoL), physical function, and work disability. METHODS: Data from the Adelphi 2018 PsA Disease-Specific Programme, a multinational, cross-sectional study of PsA patients, were used. PsA manifestations included peripheral arthritis (number of joints affected), psoriasis (body surface area [BSA]), axial involvement (inflammatory back pain [IBP] and sacroiliitis) enthesitis, and dactylitis. General, and disease-specific QoL, physical function, and work disability were measured with EQ-5D-5L, PsAID-12, HAQ-DI, and WPAI, respectively. Multivariate regression adjusting for potential confounders evaluated the independent effect of PsA manifestations on each outcome. RESULTS: Among the 2222 PsA patients analysed, 77.0% had active psoriasis and 64.4% had peripheral arthritis; 5.9%, 6.8%, 10.2%, and 3.6% had enthesitis, dactylitis, IBP, or sacroiliitis, respectively. Mean EQ VAS scores were significantly poorer in patients with vs. without enthesitis (59.9 vs. 75.6), dactylitis (63.6 vs. 75.4), and with greater peripheral joint involvement (none: 82.5; 1-2 affected joints: 74.1; 3-6 joints: 74.2; >6 joints: 65.0). Significantly worse mean PsAID-12 scores were associated with vs. without enthesitis (4.39 vs. 2.34) or dactylitis (4.30 vs. 2.32), and with greater peripheral joint involvement (none: 1.21; 1-2 joints: 2.36; 3-6 joints: 2.74; >6 joints: 3.92), and BSA (none: 1.49; >3-10%: 2.96; >10%: 3.43). Similar patterns were observed with HAQ-DI and WPAI scores. CONCLUSION: Most PsA manifestations were independently associated with worse general, and PsA-specific QoL, physical function, and work disability, highlighting the need for treatments targeting the full spectrum of PsA symptoms to lower the burden of disease.
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Artrite Psoriásica , Entesopatia , Sacroileíte , Humanos , Estados Unidos/epidemiologia , Artrite Psoriásica/diagnóstico , Qualidade de Vida , Estudos Transversais , Estado Funcional , Europa (Continente)/epidemiologia , Entesopatia/etiologia , Entesopatia/diagnóstico , Índice de Gravidade de DoençaRESUMO
Gestational epigenetic age (GEA) acceleration and deceleration can indicate developmental risk and may help elucidate how prenatal exposures lead to offspring outcomes. Depression and neighbourhood conditions during pregnancy are well-established determinants of birth and child outcomes. Emerging research suggests that maternal depression may contribute to GEA deceleration. It is unknown whether prenatal neighbourhood adversity would likewise influence GEA deceleration. This study examined whether maternal depression and neighbourhood conditions independently or jointly contributed to GEA deceleration, and which social and environmental neighbourhood conditions were associated with GEA. Participants were from the Albany Infant and Mother Study (n = 204), a prospective non-probability sampled cohort of higher risk racial/ethnic diverse mother/infant dyads. GEA was estimated from cord blood. Depressive symptoms and census-tract level neighbourhood conditions were assessed during pregnancy. Maternal depression (ß = -0.03, SE = 0.01, p = 0.008) and neighbourhood adversity (ß = -0.32, SE = 0.14, p = 0.02) were independently associated with GEA deceleration, controlling for all covariates including antidepressant use and cell type proportions. Neighbourhood adversity did not modify the association of maternal depression and GEA (ß = 0.003, SE = 0.03, p = 0.92). igher levels of neighbourhood poverty, public assistance, and lack of healthy food access were each associated with GEA deceleration; higher elementary school test scores (an indicator of community tax base) were associated with GEA acceleration (all p < 0.001). The results of this study indicated that maternal depression and neighbourhood conditions were independently and cumulatively associated GEA in this diverse population.
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Desaceleração , Depressão , Gravidez , Lactente , Criança , Feminino , Humanos , Estudos Prospectivos , Depressão/epidemiologia , Depressão/genética , Metilação de DNA , Idade Gestacional , Epigênese GenéticaRESUMO
Neighborhood and individual level risks commonly co-occur for pregnant women and may cumulatively contribute to birth outcomes. Moreover, the relationship between favorable social and environmental neighborhood conditions and perinatal outcomes has been understudied. This study considered the accumulated impact of prenatal exposure to positive neighborhood social, environmental, and educational conditions in relation to maternal health during pregnancy and birth size outcomes. In a prospective study of a multi-ethnic and socioeconomically diverse cohort (n = 239) of pregnant women and their infants, neighborhoods were characterized by the Child Opportunity Index (COI), a census-tract composite indicator representing favorable social, environmental, and educational community conditions. Adjusted generalized estimating equations showed that favorable neighborhood conditions promoted the growth of longer and heavier infant bodies, and reduced the risk of intrauterine growth restriction. The associations were stronger for female versus male infants, though not significantly different. Moreover, COI was associated with better maternal mental health and diet during pregnancy; diet significantly mediated the association between COI and birth size outcomes. This study underscores the importance of considering the accumulated benefit of neighborhood assets for maternal and infant health. Interventions that capitalizes on the full range of contextual assets in which mothers live may promote pregnancy health and fetal growth.
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Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Humanos , Lactente , Masculino , Mães , Gravidez , Resultado da Gravidez/epidemiologia , Gestantes , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Características de ResidênciaRESUMO
Many gestational exposures influence birth outcomes, yet the joint contribution of toxicant and psychosocial factors is understudied. Moreover, associated gestational epigenetic mechanisms are unknown. Lead (Pb) and depression independently influence birth outcomes and offspring NR3C1 (glucocorticoid receptor) DNA methylation. We hypothesized that gestational Pb and depression would jointly influence birth outcomes and NR3C1 methylation. Pregnancy exposure information, DNA methylation, and birth outcome data were collected prospectively from n = 272 mother-infant pairs. Factor analysis was used to reduce the dimensionality of NR3C1. Multivariable linear regressions tested for interaction effects between gestational Pb and depression exposures with birth outcomes and NR3C1. Interaction effects indicated that higher levels of Pb and depression jointly contributed to earlier gestations, smaller infant size at birth, and asymmetric fetal growth. Pb and depression were also jointly associated with the two primary factor scores explaining the most variability in NR3C1 methylation; NR3C1 scores were associated with some infant outcomes, including gestational age and asymmetric fetal growth. Pb and depression can cumulatively influence birth outcomes and epigenetic mechanisms, which may lay the foundation for later health risk. As toxicants and social adversities commonly co-occur, research should consider the life course consequences of these interconnected exposures.
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Metilação de DNA , Chumbo , Depressão/induzido quimicamente , Depressão/epidemiologia , Epigênese Genética , Feminino , Humanos , Chumbo/toxicidade , Mães , Gravidez , Receptores de GlucocorticoidesRESUMO
OBJECTIVES: To describe the effectiveness of secukinumab in the treatment of psoriatic arthritis (PsA) and associated physician satisfaction with secukinumab treatment, in routine clinical practice across five European countries. METHODS: A retrospective analysis of PsA patients receiving secukinumab for ≥4 months in France, Germany, Italy, Spain and the UK from March to December 2018. Data based on physician-completed questionnaires at initiation of treatment and at the data collection consultation were collected and used to assess effectiveness. RESULTS: 572 PsA patients with a mean age of 47.9 years, 57.0% were male, with 5.6% of patients with mild, 55.2% with moderate and 38.1% severe PsA prior to treatment initiation were included. 33.0% of patients received a dosage of 150 mg and 67.0% a dosage of 300 mg secukinumab. Around 84% of patients received secukinumab for 6 months or longer. Symptoms seen at current assessment in over 20% of patients were tender or swollen joints or psoriatic skin lesions. Between initiation of treatment and the current consultation, improvements in skin, joint and overall severity were reported. Physician satisfaction with secukinumab's ability to control disease was very high during the study period, greater than 90%, and was seen irrespective of disease severity at initiation, prior biologic use, treatment duration, time since diagnosis or onset of symptoms, treatment history, and BMI. CONCLUSION: Physicians were satisfied with the ability of secukinumab to control disease and it was effective in the treatment of PsA patients in routine clinical settings.
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Artrite Psoriásica , Anticorpos Monoclonais Humanizados , Artrite Psoriásica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Satisfação Pessoal , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: In patients with inadequate response or intolerance to first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to an agent of different mechanism of action or to another bDMARD. However, the reasons behind switching between bDMARD/targeted synthetic (ts)DMARD are not well documented in many studies. The objective of this study was to assess the rheumatologists' perceptions and behaviors towards choice of initial b/tsDMARD treatment and reasons for switching between bDMARDs/tsDMARDs, in the context of present treatment patterns. METHODS: This was a retrospective analysis of data collected from the 12th Adelphi Real World Disease Specific Programme for rheumatoid arthritis (RA). Qualified rheumatologists involved in treatment decision-making for ≥ 10 patients a month completed patient record forms (PRFs). Patients aged ≥ 18 years with RA diagnosis and receiving bDMARD/tsDMARD were included. The outcomes assessed were proportion of patients receiving bDMARD/tsDMARD at molecule and class levels; rheumatologist-reported reasons for choice of therapy; proportion of patients who switched bDMARDs/tsDMARDs; and rheumatologist-reported reasons for switching therapies. RESULTS: Eighty-six rheumatologists completed PRFs for 1027 patients. Of these, 621 were receiving bDMARD/tsDMARD at data collection. The majority (73%) of patients received first-line bDMARD/tsDMARD, and at first-line, 68% received a tumor necrosis factor inhibitor (TNFi) and 21% received a Janus kinase inhibitor (JAKi). The response option of strong overall efficacy was the primary reason for selecting first-line and second-line bDMARD/tsDMARD. A total of 163 patients had switched from first-line b/tsDMARD to second-line b/tsDMARD therapy. Of these, 44, 28, and 17% had switched from TNFi to another TNFi, TNFi to non-TNF biologic, and TNFi to JAKi, respectively. Lack of efficacy and worsening disease were the most frequent reasons for switching therapies. CONCLUSIONS: TNFis remain the most prescribed b/tsDMARD for first-line and second-line treatments. Strong overall efficacy was the primary reason for selecting therapy and loss of efficacy was the primary reason for switching therapy.
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INTRODUCTION: Enthesitis is a core outcome domain assessed in psoriatic arthritis (PsA) clinical trials. Limited evidence describes the impact of enthesitis on patient-reported outcomes (PROs) and physician satisfaction with current treatment options. The objective of this analysis is to characterize the impact of enthesitis on PROs and physician satisfaction with currently available treatment in clinical practice settings. METHODS: Cross-sectional survey of rheumatologists, dermatologists, and their consulting patients with PsA in Australia, Canada, European Union (EU5), and the USA conducted in 2018. Physicians assessed current presence and severity of enthesitis, overall disease severity, other symptoms experienced, and their satisfaction with the current treatment. PsA participant self-reported data included current pain level, EQ5D, Psoriatic Arthritis Impact of Disease (PsAID12), Health Assessment Questionnaire Disability Index (HAQ-DI), and Work Productivity and Activity Impairment Index (WPAI-SHP). Bivariate descriptive analyses were conducted to describe features and outcomes in participants with and without enthesitis. RESULTS: Rheumatologists (454) and dermatologists (238) provided information for 3157 participants with PsA. Mean participant age was 49.2 years, and 45.9% were female. Enthesitis was present currently in 6.5% (205) of participants with PsA. Those with enthesitis had worse overall disease severity compared to those without enthesitis (12.2% vs 2.2% severe) and had more extraarticular manifestations, including nail psoriasis, dactylitis, and sacroiliitis. Enthesitis was associated with more pain, worse quality of life (QoL), increased disability, and a negative impact on work. Participants with enthesitis had higher NSAIDs and opioid pain medication use but similar biologic use. Physicians were significantly less satisfied with current PsA treatment in participants with enthesitis versus without enthesitis. CONCLUSIONS: Participants with psoriatic arthritis with enthesitis experienced significantly higher disease burden than those without enthesitis but were not more likely to receive advanced therapies. Physicians were significantly more dissatisfied with treatment in patients with enthesitis than in those without it.
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PURPOSE OF REVIEW: Early-life social and environmental exposures have independent effects on many child health outcomes. Increasingly, investigators have suggested that these exposures, which commonly co-occur, may have synergistic effects and have thus begun to evaluate if environmental and social factors jointly contribute to child health. This systematic review summarizes findings and methodological approaches across studies examining the interplay between environmental and social exposures in relation to commonly assessed childhood health outcomes: asthma, cognition and behavior, perinatal outcomes, and obesity. RECENT FINDINGS: Forty-one studies met the search criteria and were reviewed. Of these, 37, 34, and 29 % of studies focused on asthma, cognition/behavior, and perinatal outcomes, respectively. No study focused on obesity. Across all studies reviewed, 72 % observed significant synergistic associations between social and environmental exposures. Air pollution was the most frequently studied environmental exposure, and socioeconomic status was the most commonly studied social factor. The emerging evidence suggests that social and environmental risks may jointly affect child health. Recommendations for future research are discussed, including enhancing characterization of the social environment and broadening the types of environmental risks assessed.