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Intermittent oil-water wetting can have a significant effect on the internal corrosion of steel pipelines. This paper presents a combined experimental and molecular modeling study of several influential factors on the surface properties and corrosion behavior of mild steel in CO2 environments. The influence of different model oils (LVT-200 and Aromatic-200) and select surface-active compounds (myristic acid, cyclohexane butyric acid, and oleic acid) on the corrosion behavior of carbon steel during intermittent oil-water wetting was determined by measuring the corrosion rate after intermittent wetting cycles. The interfacial tension measurements were performed to study the incorporation of the oil phase along with surface-active molecules in the protective layer formed on the specimen surface. Results showed that the interfacial tension for an aromatic oil-water interface is lower than that for an aliphatic oil-water interface. To understand this result, molecular dynamics simulations of oil-water interfaces were performed in the presence of surface-active molecules and different oils to analyze the structure of the layer formed at the interface. The simulations supported the hypothesis that aromatic molecules are less structured at the interface, which results in the incorporation of more water molecules into the protective layer formed at the steel surface, causing a higher corrosion rate. On the other hand, the simulations revealed that myristic acid in an aliphatic oil forms a well-aligned structure at the interface, devoid of any water molecules. This is in agreement with the hypothesis that the linear molecular structure of myristic acid favors the alignment of molecules at an aliphatic oil-water interface, resulting in a lower interfacial tension and more effective corrosion mitigation as compared to the other two nonlinear compounds tested. It is concluded that an important factor controlling the corrosion behavior is the molecular structure of the oil-water interface, which is adopted by the steel surface layer through the Langmuir-Blodgett process.
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Introduction Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged >65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) and executive function by Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results Among 5,443 participants >65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95%CI -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95%CI 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95%CI -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year (95%CI 0.003, 0.33), as did SI participants (additional 0.27 points/year (95%CI 0.19, 0.35). Conclusion Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention.
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Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex.
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Poluentes Atmosféricos , Poluição do Ar , Bancos de Espécimes Biológicos , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , Estudos Transversais , Exposição Ambiental/análise , Humanos , Material Particulado/análise , Material Particulado/toxicidade , Córtex Pré-Frontal , Reino UnidoRESUMO
The voltage gated sodium channel NaV1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole NaV1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.
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Benzimidazóis/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/química , Benzimidazóis/farmacocinética , Desenho de Fármacos , Células HEK293 , Humanos , Estrutura Molecular , Solubilidade , Relação Estrutura-Atividade , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacocinéticaRESUMO
This study demonstrates that overtraining in temporal discrimination modifies temporal stimulus control in a bisection task and produces habitual responding, as evidenced through insensitivity to food devaluation. Rats were trained or overtrained in a 2- versus 8-sec temporal discrimination task, with each duration associated with a lever (left or right) and food (grain or sucrose). Overtraining produced a leftward shift in the bisection point. Devaluation treatment induced a differential loss of responding depending on stimulus duration (short versus long) and the level of training (training versus overtraining). The relationships between timing behavior and habitual behavior are discussed.
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Aprendizagem por Discriminação , Discriminação Psicológica , Prática Psicológica , Percepção do Tempo , Animais , Hábitos , Ratos , Fatores de TempoRESUMO
It has been highlighted that in the original article [1] there was a typesetting mistake in the Results - NNT in Strive section. This Correction article states the incorrect and correct sentence.
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BACKGROUND: This analysis estimated the number needed to treat with enzalutamide versus bicalutamide to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer who would obtain clinical benefit regarding progression-free survival, radiographic progression-free survival, or no prostate-specific antigen progression at 1 and 2 years following treatment initiation. METHODS: Clinical event rates were obtained from the STRIVE (NCT01664923) and TERRAIN (NCT01288911) trials, and the number needed to treat was the inverse of the absolute rate difference between the event rates of enzalutamide and bicalutamide. The 95% Confidence Interval of the number needed to treat was derived from the 95% Confidence Interval of the event rate difference. RESULTS: Using STRIVE data (patients with metastatic disease: n = 128 enzalutamide; n = 129 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer with progression-free survival were 2.0 and 2.8, respectively; with radiographic progression-free survival, 2.6 and 3.0, respectively; and without prostate-specific antigen progression, 1.8 and 2.4, respectively. Using TERRAIN data (n = 184 enzalutamide; n = 191 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with progression-free survival were 4.3 and 3.7, respectively; with radiographic progression-free survival, 10.0 and 2.8, respectively; and without prostate-specific antigen progression, 2.1 and 3.2, respectively. CONCLUSIONS: The combined data from TERRAIN and STRIVE demonstrated that treating chemotherapy-naïve metastatic castration-resistant prostate cancer with enzalutamide leads to more patients without clinical progression at 1 and 2 years than with bicalutamide. TRIAL REGISTRATION: STRIVE (NCT01664923; registration date: August 10, 2012) and TERRAIN (NCT01288911; registration date: February 1, 2011).
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Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de PesquisaRESUMO
The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.
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Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Autorrelato , Estudos Soroepidemiológicos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Toxoplasma/fisiologia , Toxoplasmose/parasitologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The amygdalo-nigrostriatal (ANS) network plays an essential role in enhanced attention to significant events. Interval timing requires attention to temporal cues. We assessed rats having a disconnected ANS network, due to contralateral lesions of the medial central nucleus of the amygdala (CEm) and dopaminergic afferents to the lateral striatum, as compared to controls (sham and ipsilateral lesions of CEm and dopaminergic afferents to LS) in a temporal bisection task. ANS disconnection induced poorer temporal precision and increased response latencies to a short duration. The present results reveal a role of the ANS network in temporal processing.
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Núcleo Central da Amígdala/fisiologia , Corpo Estriado/fisiologia , Neurônios Dopaminérgicos/fisiologia , Desempenho Psicomotor/fisiologia , Percepção do Tempo/fisiologia , Animais , Comportamento de Escolha/fisiologia , Discriminação Psicológica/fisiologia , Masculino , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Fatores de TempoRESUMO
Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.
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Transtornos Cognitivos/parasitologia , Transtornos Cognitivos/virologia , Doenças Transmissíveis/psicologia , Adulto , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/parasitologia , Doenças Transmissíveis/virologia , Efeitos Psicossociais da Doença , Infecções por Citomegalovirus/psicologia , Etnicidade , Feminino , Hepatite/psicologia , Infecções por Herpesviridae/psicologia , Humanos , Aprendizagem , Masculino , Pessoa de Meia-Idade , Tempo de Reação , Fatores de Risco , Toxoplasmose/psicologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with cognitive deficits in humans, an association potentially mediated or moderated by folate concentration or inflammation. MATERIALS AND METHODS: We used the National Health and Nutrition Examination Survey (NHANES) datasets to examine whether folate concentration or inflammation mediates or moderates the relationship between H. pylori and cognitive function. Models were performed using linear, Poisson, and zero-inflated Poisson regression, and we performed separate analyses for groups aged 20-59 and 60-90 years with sample sizes ranging from 700 to 1700. RESULTS: We did not find evidence of mediation in either age group. In the 20- to 59-year group, interactions between H. pylori and ferritin (p values ranging from .004 to .039) were associated with worse processing speed, better working memory, and worse reaction time. Interactions between H. pylori and fibrinogen (p values ranging from .023 to .045), C-reactive protein (CRP) (p = .023), and the inflammatory index (p = .045) were associated with worse processing speed. In 60- to 90-year-olds, H. pylori interacted with ferritin and the inflammatory index to predict fewer mathematical errors (p values of .036 and .023). Interactions with folate (p values of .016 and .006) and C-reactive protein (p values ranging from <.001 to .048) were inconsistent in directionality. CONCLUSIONS: In this dataset, representative of the US population, inflammation and folate concentrations moderated but did not mediate the association between H. pylori seropositivity and cognition.
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Cognição , Ácido Fólico/metabolismo , Infecções por Helicobacter/patologia , Inflamação/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Estados Unidos , Adulto JovemRESUMO
AIM: This study seeks to improve the understanding of treatment patterns and associated health-related quality of life (HRQoL), clinical outcomes and healthcare utilization in US patients with castration-resistant prostate cancer (CRPC). PATIENTS & METHODS: Treatment Registry for Outcomes in CRPC Patients (TRUMPET) is a US-based, prospective, observational multicenter registry (NCT02380274) involving patients with CRPC and their caregivers. Patients initiating their first active treatment course will be enrolled from urology and medical oncology practices, with data captured up to 4 years. RESULTS: Information on prescribing patterns, HRQoL, clinical outcomes and healthcare utilization will be collected. CONCLUSION: TRUMPET will enable scientific understanding of disease management in terms of HRQoL, clinical outcomes and healthcare utilization in clinical practice for patients with CRPC.
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Neoplasias de Próstata Resistentes à Castração/epidemiologia , Cuidadores , Gerenciamento Clínico , Custos de Cuidados de Saúde , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/terapia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Sistema de Registros , Pesquisa , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Toxoplasma gondii (Nicolle et Manceaux, 1908) is an intracellular parasite that can cause ongoing latent infection persisting for the duration of a non-definitive host's life. Affecting approximately one-third of the world's population, latent toxoplasmosis has been associated with neuropsychological outcomes and a previous report suggested an association between latent toxoplasmosis and adult height. Given the large number of people with latent toxoplasmosis and its potential associations with human height, we sought to better understand the association between latent toxoplasmosis and human morphology by evaluating seropositivity for T. gondii and multiple body measures reported in the National Health and Nutrition Examination Survey III (NHANES III) and in the more recent continuous NHANES data sets from the United States Centers for Disease Control and Prevention for which data on T. gondii are available. In these analyses, latent toxoplasmosis was not associated with any of the body measures assessed in the NHANES datasets even after taking into account interactions between latent toxoplasmosis and testosterone suggesting that in these samples, latent toxoplasmosis is not associated with adult morphology including height.
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Tamanho Corporal , Toxoplasmose/patologia , Adulto , Anticorpos Antiprotozoários/sangue , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Toxoplasma/fisiologia , Toxoplasmose/sangueRESUMO
Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplasma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G antibody (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999-2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81-1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96-1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85-1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98-1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.
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Depressão/complicações , Toxoplasmose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antiprotozoários/sangue , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Inquéritos e Questionários , Toxoplasma , Toxoplasmose/sangue , Toxoplasmose/patologia , Adulto JovemRESUMO
The ascarid nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) may infect humans resulting in toxocariasis. A prior study associated species of Toxocara Stiles, 1905 with cognitive deficits in children. To determine if a similar association between toxocariasis and cognition exists in adults, we analysed a large dataset from the United States' Center for Disease Control's National Health and Nutrition Examination Survey. We used linear-regression and multivariate models to examine the association between toxocariasis as assessed by the presence of anti-Toxocara IgG antibodies and three measures of cognitive function - simple reaction time (SRT), symbol-digit substitution (SDS) and serial-digit learning (SDL) in 4 279 adults aged 21 to 59 years. Toxocara seroprevalence did not vary with age or blood-lead concentration but did vary with gender, ethnicity, educational attainment and poverty-to-income ratio. Controlling for gender, age, blood-lead concentration, educational attainment, ethnic background and the poverty-to-income ratio, we found that toxocariasis predicted worse performance on the SDS but not on the SRT or the SDL. Moreover, there were significant interactions between toxocariasis and age, gender and educational attainment. In conclusion, toxocariasis appears to be associated with decreased cognitive function. Interactions between toxocariasis and gender, age and educational attainment further suggest that certain groups may be more susceptible than others to the cognitive dysfunction associated with toxocariasis in adults.
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Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.
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Transtornos de Ansiedade/etiologia , Transtorno Depressivo Maior/etiologia , Transtorno de Pânico/etiologia , Toxoplasmose/complicações , Adulto , Anticorpos Antiprotozoários/sangue , Transtornos de Ansiedade/parasitologia , Transtorno Depressivo Maior/parasitologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Razão de Chances , Transtorno de Pânico/parasitologia , Fatores de Risco , Toxoplasma/imunologia , Toxoplasmose/imunologia , Toxoplasmose/patologia , Adulto JovemRESUMO
INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death among prostate cancer (PC) patients. Androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone receptor (GnRH) agonist or antagonist is the standard treatment for advanced PC. Since 2010, the Food and Drug Administration has required labeling for GnRH agonists to include warnings about increased risk for diabetes and some CVDs. METHODS: In this observational, retrospective, real-world study, we evaluated time to a first cardiovascular (CV) event within 3 years postinitiation of ADT in PC patients while controlling for CVD history and risk factors. Data from a large administrative US claims dataset (2010-2019) were analyzed using Kaplan-Meier survival analysis to calculate the HR for time to first CV event and Cox regressions to identify factors associated with time to first CV event. RESULTS: Of 10,530 patients, 92% had no history of CVD, 8% had history of CVD, and 95% were exposed to a GnRH agonist during follow-up. Kaplan-Meier analysis indicated that patients with a baseline history of CVD had increased risk of CV events within 3 years of ADT initiation vs those without such history (HR, 3.20; 95% CI, 2.58-3.96; P < .0001). Among covariates associated with higher likelihood of CV event, baseline history of CVD yielded the highest HR (2.83; 95% CI, 2.40-3.32, P < .0001). CONCLUSIONS: PC patients with a history of CVD are at increased risk of a CV event within 3 years of ADT initiation compared with those with no history of CVD.
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Doenças Cardiovasculares , Neoplasias da Próstata , Estados Unidos , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos , Androgênios/uso terapêutico , Estudos Retrospectivos , Incidência , Hormônio Liberador de Gonadotropina/agonistas , Doenças Cardiovasculares/induzido quimicamente , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Scrupulosity, despite its considerable prevalence and morbidity, remains under-investigated. The present study develops and examines the psychometric properties of a comprehensive assessment tool, the Scrupulosity Inventory (SI). METHODS: The SI, along with other measures of obsessive-compulsive disorder (OCD) and perfectionism, were administered to a sample (N = 150) of college undergraduates similar in size to other scale development studies of related measures. We conducted exploratory and confirmatory factor analyses of the SI, examined its convergent and divergent validity, and assessed its ability to predict categorical diagnoses of scrupulosity using a receiver operator characteristic analysis. RESULTS: We found a well-fitting confirmatory bifactor model (RMSEA = 0.049) with a strong general Scrupulosity factor ( [Formula: see text] ) and specific factors for Personal Violations ( [Formula: see text] ), Ritualized Behavior ( [Formula: see text] ), Interference with Life ( [Formula: see text] ), and Problem Pervasiveness ( [Formula: see text] ). As predicted, we also found the strongest convergence (r = 0.63) between the SI and the Penn Inventory of Scrupulosity (PIOS), intermediate convergence (r = 0.54) between the SI and Perfectionism Inventory (PI), and weaker convergence (r = 0.47) between the SI and YBOCS. Finally, we found that a categorical diagnosis of scrupulosity was highly predicted by the SI (AUC = 0.84), less well-predicted by the PIOS (AUC = 0.75) and less well predicted by the YBOCS (AUC = 0.69). LIMITATIONS: This study was conducted among a sample of undergraduates at a religiously affiliated university. CONCLUSIONS: These results suggest utility in using the SI to measure the severity of scrupulosity symptoms and that scrupulosity and OCD may present significantly different clinical features.
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Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Comportamento Obsessivo/diagnóstico , Análise Fatorial , Psicometria , Estudantes , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: This qualitative research study was conducted to develop a novel, comprehensive, patient-reported outcome measure (PRO), the "Symptoms and Impacts of Androgen Deprivation Therapy (ADT) for Prostate Cancer" (SIADT-PC), assessing hormonal therapy-related symptoms and their impacts on men with advanced prostate cancer. METHODS: Concept elicitation (CE) interviews were conducted among adult men with prostate cancer to evaluate their experiences with ADT. Based on key symptom and impact concepts mentioned, an initial PRO measure was developed. The draft measure was further assessed in cognitive debriefing (CD) interviews with men with prostate cancer, in which participants reviewed items, response options, and recall periods. Initial item-based psychometric analyses were conducted using interview data. The draft questionnaire was revised on the basis of participant feedback, quantitative psychometric results, and consultation with clinical experts. RESULTS: A total of 21 participants were interviewed (CE concept elicitation, n = 12; CD cognitive debriefing, n = 17; n = 8 completed both). Mean participant age (SD) was 59.7 (8.7) years and 76.2% were white. The de novo SIADT-PC measure consists of 27 items: 11 symptoms (e.g., fatigue, hot flashes, and erectile dysfunction), 2 long-term symptoms (e.g., weight gain), 10 impacts (e.g., impacts on physical activities and relationships), and 4 related to mode of administration (i.e., injection-site reactions). Items were assessed with a 5-point verbal rating scale, with answer choices that capture frequency or severity. CONCLUSIONS: Once fully validated, this de novo measure may be used in clinical studies and clinical practice to assess hormone therapy-related symptoms and impacts, enabling physicians to identify timely and appropriate interventions.
Assuntos
Antagonistas de Androgênios , Medidas de Resultados Relatados pelo Paciente , Neoplasias da Próstata , Psicometria , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Inquéritos e Questionários , Pesquisa Qualitativa , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/efeitos adversosRESUMO
BACKGROUND: In the HERO study, relugolix demonstrated sustained testosterone suppression superior to that of leuprolide acetate (97% vs 89%; difference 7.9% [95% confidence interval, 4.1-12%; p < 0.001]). OBJECTIVE: To analyze testosterone recovery in a prespecified subset of men from the HERO study not indicated to continue androgen deprivation therapy. DESIGN, SETTING, AND PARTICIPANTS: Men (N = 934) were randomized (2:1) to receive relugolix 120 mg orally daily or leuprolide acetate injections every 12 wk for 48 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Testosterone recovery was assessed in 184 men who completed 48 wk of treatment. During the 90-d recovery period, assessments included time to testosterone recovery (>280 ng/dl; ≥80% of baseline testosterone), serum levels of prostate-specific antigen and pituitary hormones, and adverse events. RESULTS AND LIMITATIONS: The cumulative incidence rate of testosterone recovery to >280 ng/dl at 90 d following drug discontinuation was significantly higher in the relugolix cohort (n = 137) than in the leuprolide acetate cohort (n = 47; 54% vs 3.2%; nominal p = 0.002). The median time to testosterone recovery was faster following relugolix treatment than with leuprolide acetate treatment (86.0 d vs 112.0 d). Compared with leuprolide acetate, more men treated with relugolix achieved ≥80% of baseline testosterone levels (39% vs 2.1%). Men ≤65 yr and those with baseline testosterone greater than the median had a higher incident rate of testosterone recovery. Adverse events were generally similar between treatment groups. One limitation is the short testosterone recovery follow-up period. CONCLUSIONS: Oral relugolix had faster and more complete recovery of testosterone to normal levels after treatment discontinuation than leuprolide acetate in a subset of men from the HERO study. The clinical implications of a faster testosterone recovery with relugolix may be significant for men being treated with androgen deprivation therapy and influence treatment decisions. PATIENT SUMMARY: The male hormone testosterone is reduced during androgen deprivation therapy for prostate cancer. Reduced testosterone levels cause side effects, impacting patient quality of life. When treatment is stopped, the side effects lessen over time as the levels of testosterone come back to pretreatment range (testosterone recovery). In this study, we found that the time to testosterone recovery was faster with relugolix than with leuprolide acetate.