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1.
Milbank Q ; 102(2): 398-428, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38424372

RESUMO

Policy Points Health equity work primarily centers monoracial populations; however, the rapid growth of the Multiracial population and increasingly clear health disparities affecting the people in that population complicate our understanding of racial health equity. Limited resources exist for health researchers and professionals grappling with this complexity, likely contributing to the relative dearth of health literature describing the Multiracial population. We introduce a question-based framework built on core principles from Critical Multiracial Theory (MultiCrit) and Critical Race Public Health Praxis, designed for researchers, clinicians, and policymakers to encourage health data equity for the Multiracial population.


Assuntos
Equidade em Saúde , Humanos , Disparidades nos Níveis de Saúde , Estados Unidos , Grupos Raciais
2.
Am J Obstet Gynecol ; 230(6): 583-599.e16, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38109950

RESUMO

OBJECTIVE: A decline in musculoskeletal health during pregnancy is an underappreciated adverse outcome of pregnancy that can have immediate and long-term health consequences. High physical job demands are known risk factors for nontraumatic musculoskeletal disorders in the general working population. Evidence from meta-analyses suggest that occupational lifting and prolonged standing during pregnancy may increase risk of adverse pregnancy outcomes. This systematic review examined associations between occupational lifting or postural load in pregnancy and associated musculoskeletal disorders and related sequalae. DATA SOURCES: Five electronic databases (Medline, Embase, CINAHL, NIOSHTIC-2, and Ergonomic Abstracts) were searched from 1990 to July 2022 for studies in any language. A Web of Science snowball search was performed in December 2022. Reference lists were manually reviewed. STUDY ELIGIBILITY CRITERIA: Eligible studies reported associations between occupational lifting or postural load and musculoskeletal health or sequelae (eg, employment outcomes) among pregnant and postpartum workers. METHODS: Data were extracted using a customized form to document study and sample characteristics; and details of exposures, outcomes, covariates, and analyses. Investigators independently assessed study quality for 7 risk-of-bias domains and overall utility, with discrepant ratings resolved through discussion. A narrative synthesis was conducted due to heterogeneity. RESULTS: Sixteen studies (11 cohort studies, 2 nested case-control studies, and 3 cross-sectional studies) from 8 countries were included (N=142,320 pregnant and N=1744 postpartum workers). Limited but consistent evidence with variable quality ratings, ranging from critical concern to high, suggests that pregnant workers exposed to heavy lifting (usually defined as ≥22 lbs or ≥10 kg) may be at increased risk of functionally limiting pelvic girdle pain and antenatal leave. Moreover, reports of dose-response relationships suggest graded risk levels according to lifting frequency, ranging from 21% to 45% for pelvic girdle pain and 58% to 202% for antenatal leave. Limited but consistent evidence also suggests that postural load increases the risk of employment cessation. CONCLUSION: Limited but consistent evidence suggests that pregnant workers exposed to heavy lifting and postural load are at increased risk of pelvic girdle pain and employment cessation. Job accommodations to reduce exposure levels may promote safe sustainable employment for pregnant workers.


Assuntos
Emprego , Remoção , Doenças Musculoesqueléticas , Doenças Profissionais , Humanos , Feminino , Gravidez , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Complicações na Gravidez/epidemiologia , Postura/fisiologia , Fatores de Risco
3.
Occup Environ Med ; 81(4): 178-183, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38499331

RESUMO

OBJECTIVE: To describe the lifetime prevalence of workplace harassment, physical violence and sexual assault against transgender and non-binary workers targeted due to their gender identity and to identify correlates of this workplace violence. METHODS: This descriptive cross-sectional study used data from 4597 transgender or non-binary respondents from the 2008-2009 National Transgender Discrimination Survey. Respondents reported if they had ever experienced harassment, physical violence or sexual assault at work specifically because of their gender identity. We estimated the prevalence of each type of violence stratified by gender identity, race/ethnicity, age, educational attainment, history of working in the street economy (eg, sex industry, drug sales) and if people at work knew their gender identity. RESULTS: Workplace violence was prevalent, with 50% of transgender and non-binary workers having ever experienced harassment, 7% physical violence and 6% sexual assault at work because of their gender identity. Harassment was common among all of these workers, but physical violence and sexual assault were more than twice as common among transfeminine and non-binary workers assigned male at birth, workers of colour, workers with low educational attainment and those who had ever worked in the street economy. CONCLUSIONS: Transgender and non-binary workers commonly face violence at work because of their gender identity. Workplace violence prevention programmes should incorporate ways to prevent gender identity-based violence and facilitate channels for workers to report the occurrence of discrimination and violence.


Assuntos
Pessoas Transgênero , Violência no Trabalho , Humanos , Masculino , Feminino , Adulto , Pessoas Transgênero/estatística & dados numéricos , Pessoas Transgênero/psicologia , Estudos Transversais , Prevalência , Pessoa de Meia-Idade , Violência no Trabalho/estatística & dados numéricos , Adulto Jovem , Adolescente , Estados Unidos/epidemiologia , Inquéritos e Questionários , Delitos Sexuais/estatística & dados numéricos , Identidade de Gênero , Local de Trabalho/psicologia , Local de Trabalho/estatística & dados numéricos
4.
Occup Environ Med ; 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184367

RESUMO

OBJECTIVES: Flight attendants perform physically demanding work such as lifting baggage, pushing service carts and spending the workday on their feet. We examined if more frequent exposure to occupational physical demands could explain why previous studies have found that flight attendants have a higher reported prevalence of menstrual cycle irregularities than other workers. METHODS: We conducted a cross-sectional analysis of 694 flight attendants and 120 teachers aged 18-44 years from three US cities. Eligible participants were married, had not had a hysterectomy or tubal ligation, were not using hormonal contraception and were not recently pregnant. Participants reported menstrual cycle characteristics (cramps, pain, irregular cycles, flow, bleed length, cycle length) and occupational physical demands (standing, lifting, pushing/pulling, bending/twisting, overall effort). We used modified Poisson regression to examine associations between occupation (flight attendant, teacher) and menstrual irregularities; among flight attendants, we further examined associations between occupational physical demands and menstrual irregularities. RESULTS: All occupational physical demands were more commonly reported by flight attendants than teachers. Flight attendants reported more frequent menstrual cramps than teachers, and most occupational physical demands were associated with more frequent or painful menstrual cramps. Lifting heavy loads was also associated with irregular cycles. CONCLUSIONS: Occupational physical demands were associated with more frequent and worse menstrual pain among flight attendants. The physical demands experienced by these workers may contribute to the high burden of menstrual irregularities reported by flight attendants compared with other occupational groups, such as teachers.

5.
Am J Epidemiol ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38055631

RESUMO

Disparities in maternal-child health outcomes by race and ethnicity highlight structural differences in the opportunity for optimal health in the United States. Examples of these differences include access to state-level social policies that promote maternal-child health. States vary in their racial and ethnic composition as a result of the complex history of policies and laws related to slavery, Indigenous genocide and relocation, segregation, immigration, and settlement in the United States. States also vary in the social policies they enact. As a result, correlations exist between the demographic makeup of a state's population and the presence or absence of social policies in that state. These correlations become a mechanism by which racial and ethnic disparities in maternal-child health outcomes can operate. In this commentary, we use the example of three labor-related policies actively under consideration at state and federal levels (paid parental leave, paid sick leave, and reasonable accommodations during pregnancy) to demonstrate how correlations between state demographics and presence of these state policies could cause or exacerbate racial and ethnic disparities in maternal-child health outcomes. We conclude with a call for researchers to consider how the geographic distribution of racialized populations and state policies could contribute to maternal-child health disparities.

6.
Occup Environ Med ; 80(10): 572-579, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37669856

RESUMO

OBJECTIVES: Our research questions are often chosen based on the existence of suitable data for analysis or prior research in the area. For new interdisciplinary research areas, such as occupational health equity, suitable data might not yet exist. In this manuscript, we describe how we approached a research question in the absence of suitable data using the example of identifying inequities in adequate bathrooms in US workplaces. METHODS: We created a conceptual model that hypothesises causal mechanisms for occupational health inequities, and from this model we identified a series of questions that could be answered using separate data sets to better understand inequities in adequate workplace bathrooms. Breaking up the analysis into multiple steps allowed us to use multiple data sources and analysis methods, which helped compensate for limitations in each data set. RESULTS: Using the conceptual model as a guide, we were able to identify some jobs that likely have inadequate bathrooms as well as subpopulations potentially at higher risk for inadequate bathrooms. We also identified specific data gaps by reflecting on the challenges we faced in our multistep analysis. These gaps, which indicated future data collection needs, included difficulty finding data sources for some predictors of inadequate bathrooms that prevented us from fully investigating potential inequities. CONCLUSIONS: We share our conceptual model and our example analysis to motivate researchers to avoid letting availability of data limit the research questions they pursue.

7.
Occup Environ Med ; 79(1): 17-23, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34193593

RESUMO

OBJECTIVE: Nail technicians and hairdressers may be exposed to chemicals with potential reproductive effects. While studies have examined birth defects in children of hairdressers, those in children of nail technicians have not been evaluated. We investigated associations between selected birth defects and maternal occupation as a nail technician or hairdresser versus a non-cosmetology occupation during pregnancy. METHODS: We analysed population-based case-control data from the multisite National Birth Defects Prevention Study, 1997-2011. Cases were fetuses or infants with major structural birth defects; controls were live-born infants without major birth defects. Expert raters classified self-reported maternal jobs as nail technician, combination nail technician-hairdresser, hairdresser, other cosmetology work or non-cosmetology work. We used logistic regression to calculate adjusted ORs and 95% CIs for associations between occupation during pregnancy and birth defects, controlling for age, smoking, education and race/ethnicity. RESULTS: Sixty-one mothers worked as nail technicians, 196 as hairdressers, 39 as combination nail technician-hairdressers and 42 810 as non-cosmetologists. The strongest associations among nail technicians included seven congenital heart defect (CHD) groups (ORs ranging from 2.7 to 3.5) and neural tube defects (OR=2.6, CI=0.8 to 8.4). Birth defects most strongly associated with hairdressing included anotia/microtia (OR=2.1, CI=0.6 to 6.9) and cleft lip with cleft palate (OR=2.0, CI=1.1 to 3.7). All oral cleft groups were associated with combination nail technician-hairdresser work (ORs ranging from 4.2 to 5.3). CONCLUSIONS: Small samples resulted in wide CIs. Still, results suggest associations between maternal nail technician work during pregnancy and CHDs and between hairdressing work and oral clefts.


Assuntos
Barbearia/estatística & dados numéricos , Indústria da Beleza/estatística & dados numéricos , Anormalidades Congênitas/epidemiologia , Exposição Materna , Exposição Ocupacional , Gestantes , Adulto , Estudos de Casos e Controles , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Microtia Congênita/epidemiologia , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Defeitos do Tubo Neural/epidemiologia , Gravidez , Estados Unidos/epidemiologia
8.
Am J Ind Med ; 65(9): 743-748, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35869949

RESUMO

BACKGROUND: Inequities in US employees' access to paid sick leave are known, but it is not clear whether they are increasing or decreasing over time. More than two dozen state and local paid sick leave laws were recently enacted, many with the stated goal of reducing inequities in access to paid sick leave. We examined how inequities in access to paid sick leave have changed over time, focusing on the years when these laws were coming into effect. METHODS: Private sector employees participating in the National Health Interview Survey between 2006 (before laws came into effect) and 2018 (after most came into effect) reported if they had paid sick leave in their main job. We examined how differences in access to paid sick leave by Census region, race/ethnicity, work hours, and educational attainment changed over time. RESULTS: The percentage of employees with access to paid sick leave increased from 56% in 2006 to 61% in 2018, with most of the increases in access occurring in the West. Inequities by race/ethnicity decreased substantially between 2015 and 2018, the years when most paid sick leave laws came into effect. This change was driven by Hispanic and Latino workers rapidly gaining access to paid sick leave during this time. Differences in access to paid sick leave by work hours and education attainment remained stable over time. CONCLUSIONS: Inequities in access to paid sick leave remain. Paid sick leave laws could be effective means to increase access to paid sick leave and equalize access.


Assuntos
Setor Privado , Licença Médica , Emprego , Humanos , Salários e Benefícios , Inquéritos e Questionários
9.
Arterioscler Thromb Vasc Biol ; 40(6): e138-e152, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32459541

RESUMO

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity. In this highlight, we introduce recent advances published in both ATVB and many other journals: (1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.


Assuntos
Células Endoteliais/imunologia , Imunidade Inata/imunologia , Apresentação de Antígeno , Arteriosclerose/imunologia , Sistema Cardiovascular/imunologia , Citocinas/metabolismo , Humanos , Tolerância Imunológica , Memória Imunológica , Inflamação/imunologia , Macrófagos/imunologia , Obesidade Abdominal , Receptores Citoplasmáticos e Nucleares , Transdução de Sinais , Trombose/imunologia
10.
Occup Environ Med ; 78(10): 731-737, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34039757

RESUMO

OBJECTIVES: To examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses. METHODS: Our study included women who enrolled in the Nurses' Health Study 3 (2010-2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs. RESULTS: Our study included 2579 nurses with a median of 5.6 years of follow-up (range: 1-9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93). CONCLUSIONS: We observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously.


Assuntos
Aborto Espontâneo/epidemiologia , Desinfetantes/efeitos adversos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Aborto Espontâneo/induzido quimicamente , Adulto , Feminino , Humanos , Exposição Ocupacional/estatística & dados numéricos , Gravidez , Fatores de Risco , Inquéritos e Questionários
11.
Am J Epidemiol ; 189(10): 1030-1032, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602521

RESUMO

Scientific conferences provide attendees opportunities to network, share research, learn new skills and ideas, and initiate collaborations. Conference attendance is especially important for students and early-career researchers who are establishing their research careers or looking for jobs. However, attending conferences can be expensive, and the high cost of conference attendance might hit students and early-career researchers the hardest. According to a new member survey from the Society for Epidemiologic Research, early-career members are more racially and ethnically diverse than senior members, meaning that reducing financial barriers to conference participation might be an important consideration for increasing diversity among conference attendees. In this commentary, we discuss how choice of conference location-choosing less expensive cities nearer to more Society for Epidemiologic Research members-could reduce financial and other barriers to conference attendance for all members and improve diversity and inclusion in the Society.


Assuntos
Congressos como Assunto , Diversidade Cultural , Epidemiologia/organização & administração , Sociedades Médicas , Humanos
12.
MMWR Morb Mortal Wkly Rep ; 69(12): 324-328, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32214076

RESUMO

Workplace violence can lead to adverse physical and psychological outcomes and affect work function (1). According to the U.S. Bureau of Labor Statistics, intentional injury by another person is a leading cause of nonfatal injury requiring missed workdays (2). Most estimates of workplace violence include only crimes reported to employers or police, which are known underestimates (3,4). Using 2007-2015 data from the National Crime Victimization Survey (NCVS), characteristics of self-reported nonfatal violent workplace crimes, whether reported to authorities or not, and rates by occupation were examined. Estimates of crime prevalence were stratified by crime characteristics and 22 occupational groups. Overall, approximately eight violent workplace crimes were reported per 1,000 workers. During 2007-2010, workers in Protective services reported the highest rates of violent workplace crimes (101 per 1,000 workers), followed by Community and social services (19 per 1,000). Rates were higher among men (nine per 1,000) than among women (six per 1,000). Fifty-eight percent of crimes were not reported to police. More crimes against women than against men involved offenders known from the workplace (34% versus 19%). High-risk occupations appear to be those involving interpersonal contact with persons who might be violent, upset, or vulnerable. Training and controls should emphasize how employers and employees can recognize and manage specific risk factors in prevention programs. In addition, workplace violence-reduction interventions might benefit from curricula developed for men and women in specific occupational groups.


Assuntos
Ocupações/estatística & dados numéricos , Violência no Trabalho/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
13.
Regul Toxicol Pharmacol ; 116: 104688, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621976

RESUMO

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.


Assuntos
Alérgenos/toxicidade , Haptenos/toxicidade , Medição de Risco/métodos , Alternativas aos Testes com Animais , Animais , Simulação por Computador , Células Dendríticas/efeitos dos fármacos , Dermatite de Contato/etiologia , Humanos , Queratinócitos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos
14.
Am J Ind Med ; 63(3): 240-248, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31828843

RESUMO

BACKGROUND: Night shift work is associated with cardiovascular disease, but its associations with cardiovascular disease biomarkers are unclear. We investigated these associations in a study of female nurses. METHODS: We used data from the Nurses' Health Study II for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, C-reactive protein (CRP), and fibrinogen. The sample sizes for our analysis ranged from 458 (fibrinogen) to 3574 (total cholesterol). From questionnaires, we determined the number of night shifts worked in the 2 weeks before blood collection and total years of rotating night shift work. We used quantile regression to estimate differences in biomarker levels by shift work history, adjusting for potential confounders. RESULTS: Nurses working 1 to 4 recent night shifts had median HDL cholesterol levels 4.4 mg/dL (95% confidence interval [CI]: 0.3, 7.5) lower than nurses without recent night shifts. However, working ≥5 recent night shifts and years of rotating night shift work were not associated with HDL cholesterol. There was no association between recent night shifts and CRP, but median CRP levels were 0.1 (95% CI: 0.0, 0.2), 0.2 (95% CI: 0.1, 0.4), and 0.2 (95% CI: 0.0, 0.4) mg/L higher among nurses working rotating night shifts for 1 to 5, 6 to 9, and ≥10 years compared with nurses never working rotating night shifts. These associations were attenuated when excluding postmenopausal women and women taking statins. We observed no associations between night shift work and other biomarkers. CONCLUSIONS: We found suggestive evidence of adverse short-term and long-term effects of night shift work on select cardiovascular disease biomarkers.


Assuntos
Doenças Cardiovasculares/etiologia , Transtornos Cronobiológicos/sangue , Enfermeiras e Enfermeiros/estatística & dados numéricos , Doenças Profissionais/sangue , Jornada de Trabalho em Turnos/efeitos adversos , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Transtornos Cronobiológicos/etiologia , Feminino , Fibrinogênio/análise , Fatores de Risco de Doenças Cardíacas , Humanos , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Inquéritos e Questionários , Triglicerídeos/sangue , Tolerância ao Trabalho Programado/fisiologia
15.
Clin Gerontol ; 43(1): 24-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31680645

RESUMO

Objectives: Eliminating Veteran suicide is a top priority for the Department of Veterans' Affairs (VA). This study identified factors associated with suicidal ideation (SI) among a rarely studied subgroup of Veterans: those with cancer.Methods: Veterans (age M = 61.83) with cancer (N= 175) referred for psychological evaluation completed measures of pain, sleep, depressive, anxiety, and PTSD symptoms. SI was defined by endorsing on paper-and-pencil questionnaire thoughts of killing oneself in the past 2 weeks or during clinical interview.Results: 25.1% reported SI. Compared to those without SI, Veterans with SI had higher ratings on measures of depression, anxiety, and PTSD symptoms. History of suicide attempt(s) was included in the model due to clinical significance. Logistic regression was performed with these variables as predictors of SI. The omnibus model was significant (p< .001). However, only anhedonia and depressed mood had a statistically significant contribution to the model (ß = 0.540, p= .001).Conclusions: Anhedonia and depressed mood predicted SI among Veterans with cancer above and beyond other risk factors.Clinical Implications: This study's findings highlight the importance of incorporating suicide risk screenings in oncology clinics across VA medical centers.


Assuntos
Transtornos Mentais/epidemiologia , Neoplasias/psicologia , Encaminhamento e Consulta , Ideação Suicida , Veteranos/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tentativa de Suicídio/estatística & dados numéricos , Estados Unidos/epidemiologia
16.
Am J Epidemiol ; 188(3): 562-569, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576409

RESUMO

Much of the literature on the healthy worker effect focuses on studies of chronic disease and mortality; however, when studying pregnancy outcomes, these effects might differ because of the short, defined risk periods of most pregnancy outcomes. Three pregnancy-specific healthy worker effects have also been described, but the structure of these effects has not yet been investigated when occupational exposure, and not employment status, is the exposure of interest. We used directed acyclic graphs to examine healthy worker effects in studies of occupational exposures and pregnancy outcomes: the healthy hire effect, the healthy worker survivor effect, the desperation/privilege effect (differential workforce reentry after pregnancy), the reproductively unhealthy worker effect (women with live births leave the workforce, while women with nonlive births do not), and the insecure pregnancy effect (women with adverse pregnancy outcomes reduce their exposures in subsequent pregnancies). Given our assumptions, we conclude that the healthy hire effect, the desperation/privilege effect, the reproductively unhealthy worker effect, and the insecure pregnancy effect result from confounding that can be addressed if data on measured confounders, such as employment status, are available. The presence of the healthy worker survivor effect, however, varies by study design. Different types of healthy worker effects can be present in studies of occupational exposure and pregnancy outcomes, and many of them are easily addressed analytically.


Assuntos
Modelos Estatísticos , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Gráficos por Computador , Interpretação Estatística de Dados , Feminino , Efeito do Trabalhador Sadio , Humanos , Recém-Nascido , Doenças Profissionais/etiologia , Gravidez , Complicações na Gravidez/etiologia
17.
Mutagenesis ; 34(1): 67-82, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30189015

RESUMO

(Quantitative) structure-activity relationship or (Q)SAR predictions of DNA-reactive mutagenicity are important to support both the design of new chemicals and the assessment of impurities, degradants, metabolites, extractables and leachables, as well as existing chemicals. Aromatic N-oxides represent a class of compounds that are often considered alerting for mutagenicity yet the scientific rationale of this structural alert is not clear and has been questioned. Because aromatic N-oxide-containing compounds may be encountered as impurities, degradants and metabolites, it is important to accurately predict mutagenicity of this chemical class. This article analysed a series of publicly available aromatic N-oxide data in search of supporting information. The article also used a previously developed structure-activity relationship (SAR) fingerprint methodology where a series of aromatic N-oxide substructures was generated and matched against public and proprietary databases, including pharmaceutical data. An assessment of the number of mutagenic and non-mutagenic compounds matching each substructure across all sources was used to understand whether the general class or any specific subclasses appear to lead to mutagenicity. This analysis resulted in a downgrade of the general aromatic N-oxide alert. However, it was determined there were enough public and proprietary data to assign the quindioxin and related chemicals as well as benzo[c][1,2,5]oxadiazole 1-oxide subclasses as alerts. The overall results of this analysis were incorporated into Leadscope's expert-rule-based model to enhance its predictive accuracy.


Assuntos
Óxidos N-Cíclicos/química , Dano ao DNA/efeitos dos fármacos , Mutagênicos/química , Relação Quantitativa Estrutura-Atividade , Óxidos N-Cíclicos/toxicidade , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade , Mutagênicos/toxicidade
19.
Regul Toxicol Pharmacol ; 102: 53-64, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30562600

RESUMO

The International Council for Harmonization (ICH) M7 guideline describes a hazard assessment process for impurities that have the potential to be present in a drug substance or drug product. In the absence of adequate experimental bacterial mutagenicity data, (Q)SAR analysis may be used as a test to predict impurities' DNA reactive (mutagenic) potential. However, in certain situations, (Q)SAR software is unable to generate a positive or negative prediction either because of conflicting information or because the impurity is outside the applicability domain of the model. Such results present challenges in generating an overall mutagenicity prediction and highlight the importance of performing a thorough expert review. The following paper reviews pharmaceutical and regulatory experiences handling such situations. The paper also presents an analysis of proprietary data to help understand the likelihood of misclassifying a mutagenic impurity as non-mutagenic based on different combinations of (Q)SAR results. This information may be taken into consideration when supporting the (Q)SAR results with an expert review, especially when out-of-domain results are generated during a (Q)SAR evaluation.


Assuntos
Contaminação de Medicamentos , Guias como Assunto , Mutagênicos/classificação , Relação Quantitativa Estrutura-Atividade , Indústria Farmacêutica , Órgãos Governamentais , Mutagênicos/toxicidade , Medição de Risco
20.
Regul Toxicol Pharmacol ; 107: 104403, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195068

RESUMO

In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals under REACH as well as the ICH M7 guideline for drug impurities. There are a number of obstacles to performing an IST assessment, including uncertainty in how such an assessment and associated expert review should be performed or what is fit for purpose, as well as a lack of confidence that the results will be accepted by colleagues, collaborators and regulatory authorities. To address this, a project to develop a series of IST protocols for different hazard endpoints has been initiated and this paper describes the genetic toxicity in silico (GIST) protocol. The protocol outlines a hazard assessment framework including key effects/mechanisms and their relationships to endpoints such as gene mutation and clastogenicity. IST models and data are reviewed that support the assessment of these effects/mechanisms along with defined approaches for combining the information and evaluating the confidence in the assessment. This protocol has been developed through a consortium of toxicologists, computational scientists, and regulatory scientists across several industries to support the implementation and acceptance of in silico approaches.


Assuntos
Modelos Teóricos , Mutagênicos/toxicidade , Projetos de Pesquisa , Toxicologia/métodos , Animais , Simulação por Computador , Humanos , Testes de Mutagenicidade , Medição de Risco
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