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Clinical trials are essential in the translation of biomedical discoveries to new clinical interventions and therapeutics. Successful multisite clinical trials require qualified site investigators with an understanding of the full spectrum of processes and requirements from trial identification through closeout. New site investigators may be deterred by competing demands on their time, the complexity of administrative and regulatory processes for trial initiation and conduct, and limited access to experienced mentor networks. We established a Clinical Trialist Training Program (CTTP) and complimentary Clinical Trials Bootcamp at our institution to address these barriers and increase the number of local site investigators enabled to lead successful clinical trials. An initial cohort of four CTTP scholars received salary support with protected time, didactic training, assistance with study identification and start-up navigation, and quarterly progress meetings. By the end of the 12-month program, this initial cohort identified 33 new trials, utilized feasibility assessments, and reported being on target to sustain their protected time from new clinical trials. Bootcamp attendees demonstrated increased knowledge of resources, offices, and processes associated with clinical trial conduct. Our results support providing compensated protected time, training, and access to experienced clinical research professionals to enable clinicians to become successful site investigators.
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Clinical Research Professionals (CRPs) are essential members of the Clinical and Translational Research Workforce. Many academic medical institutions struggle to recruit and retain these vital team members. One strategy to increase job satisfaction and promote the retention of CRPs is through educational initiatives that provide training and professional development. The South Carolina Clinical and Translational Research (SCTR) Institute Workforce Development (WD) team at the Medical University of South Carolina (MUSC) developed several trainings as part of our larger educational portfolio for CRPs. In 2022 WD implemented a digital badge micro-credential for SCTR's Core Clinical Research Training (CCRT) course in collaboration with institution-wide education and technology offices. Beginning in January 2023, individuals were able to earn the CCRT Certified Digital Badge upon successful completion of the CCRT course.
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Developing the translational research workforce is a goal established by the National Center for Advancing Translational Science for its network of Clinical and Translational Science Award Program hubs. We surveyed faculty and research staff at our institution about their needs and preferences, utilization of existing trainings, and barriers and facilitators to research training. A total of 545 (21.9%) faculty and staff responded to the survey and rated grant development, research project development, and professional development among their top areas for further training. Faculty prioritized statistical methods and dissemination and implementation, while staff prioritized research compliance and research administration. Faculty (73.9%; n = 119) and staff (87.3%; n = 165) reported that additional training would give them more confidence in completing their job responsibilities. Time and lack of awareness were the most common barriers to training. Our results indicate the value of training across a range of topics with unique needs for faculty and staff. This pre-COVID survey identified time, awareness, and access to training opportunities as key barriers for faculty and staff. The shift to remote work spurred by the pandemic has further heightened the need for effective and readily accessible online trainings to enable continuous development of the clinical and translational research workforce.
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Clinical trials are a fundamental tool in evaluating the safety and efficacy of new drugs, medical devices, and health system interventions. Clinical trial visits generally involve eligibility assessment, enrollment, intervention administration, data collection, and follow-up, with many of these steps performed during face-to-face visits between participants and the investigative team. Social distancing, which emerged as one of the mainstay strategies for reducing the spread of SARS-CoV-2, has presented a challenge to the traditional model of clinical trial conduct, causing many research teams to halt all in-person contacts except for life-saving research. Nonetheless, clinical research has continued during the pandemic because study teams adapted quickly, turning to virtual visits and other similar methods to complete critical research activities. The purpose of this special communication is to document this rapid transition to virtual methodologies at Clinical and Translational Science Awards hubs and highlight important considerations for future development. Looking beyond the pandemic, we envision that a hybrid approach, which implements remote activities when feasible but also maintains in-person activities as necessary, will be adopted more widely for clinical trials. There will always be a need for in-person aspects of clinical research, but future study designs will need to incorporate remote capabilities.
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The mission of the National Center for Advancing Translational Science (NCATS) is to speed the development of drugs from discovery to approval to dissemination and implementation. The Medical University of South Carolina and the South Carolina Clinical and Translational Research Institute host a NCATS funded predoctoral T32 training grant (TL1) with a focus on translational research. Doctoral (PhD) trainees working at the bench usually have limited opportunity for clinical interactions to gain a clinical perspective on the diseases that are the focus of their dissertation research. To provide TL1 trainees with an opportunity to see how their research could be translated into improved patient care, we developed a mentored clinical exposure experience named the Translational Sciences Clinic. Trainees spend one-half day a week in a clinic related to their basic science research for one semester interacting with patients and clinical mentors and discuss the most recent literature related to the patient's clinical problem with their clinical mentor. Trainees deemed the rotation to be one of the most rewarding experiences that they had as a part of their predoctoral training. Participating clinical mentors were also very enthusiastic and agreed that they would be willing to mentor similar trainees again.
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The pregnancy-related mortality ratio in the United States has increased over the past 25 years. Georgia's pregnancy-related mortality ratio is among the highest in the United States. Confronted with this harsh reality, Georgia reestablished maternal mortality review as one strategy to address its high maternal mortality. To achieve a comprehensive process for review of maternal deaths involved securing the knowledge, resources, and support of physician experts, public health agencies and professional organizations as well as representatives in the state legislature. The six key steps in successfully reinstating maternal mortality review were 1) establishing a maternal mortality advisory committee, 2) developing a defined methodology for comprehensive case identification, 3) convening an introductory maternal mortality review committee meeting, 4) securing legislative protection for the committee, 5) conducting a mock mortality review, and 6) completing a formal first-year case review and producing a summary report of initial findings. This first case review revealed the leading causes of pregnancy-related deaths in Georgia as hemorrhage, hypertension, cardiac disease, embolism, and seizures. Our objective in this commentary is to share our experiences and advocate for engaging public, private, and academic partners in working on complex and multifactorial public health issues such as high maternal mortality.
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Servicios de Salud Materna/organización & administración , Mortalidad Materna , Femenino , Georgia , Humanos , EmbarazoRESUMEN
STUDY QUESTION: Do cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric acid (GABA), testosterone (T) and estradiol (E2) differ in women with polycystic ovary syndrome (PCOS) as compared to eumenorrheic, ovulatory women (EW)? SUMMARY ANSWER: Women with PCOS displayed higher CSF levels of GABA and E2, and possibly T, than EW. WHAT IS KNOWN ALREADY: The chronic anovulation characteristic of PCOS has been attributed to increased central GnRH drive and resulting gonadotropin aberrations. Androgens are thought to regulate GABA, which in turn regulates the neural cascade that modulates GnRH drive. STUDY DESIGN, SIZE, DURATION: This cross-sectional observational study included 15 EW and 12 non-obese women with PCOS who consented to a lumbar puncture in addition to 24 h of serum blood collection at 15-min intervals. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 27 women were studied at a the General Clinical Research Center (GCRC) at the University of Pittsburgh. Serum analytes included T, E2 and androstenedione. CSF analytes included GABA, glutamate, glucose, T and E2. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS had higher CSF GABA as compared to EW (9.04 versus 7.04 µmol/L, P < 0.05). CSF glucose and glutamate concentrations were similar between the two groups. CSF T was 52% higher (P = 0.1) and CSF E2 was 30% higher (P < 0.01) in women with PCOS compared to EW. Circulating T was 122% higher (P < 0.01) and circulating E2 was 75% higher (P < 0.01) in women with PCOS than in EW. LIMITATIONS REASONS FOR CAUTION: The study is limited by its small sample size and the technical limitations of measuring CSF analytes that are pulsatile and have short half-lives. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS displayed significantly higher circulating levels of T and E2, significantly higher CSF levels of E2, and higher levels of CSF testosterone, although the latter was not statistically significant. A better understanding of the central milieu informs our understanding of the mechanisms mediating increased the GnRH drive in PCOS and lends a new perspective for understanding the presentation, pathogenesis and potential health consequences of PCOS, including gender identity issues. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest. The study was funded by NIH grants to SLB (RO1-MH50748, U54-HD08610) and NIH RR-00056 to the General Clinical Research Center of the University of Pittsburgh. TRIAL REGISTRATION NUMBER: NCT01674426.
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Estradiol/líquido cefalorraquídeo , Síndrome del Ovario Poliquístico/líquido cefalorraquídeo , Testosterona/líquido cefalorraquídeo , Regulación hacia Arriba , Ácido gamma-Aminobutírico/líquido cefalorraquídeo , Adulto , Androstenodiona/sangre , Estudios Transversales , Estradiol/sangre , Femenino , Glucosa/líquido cefalorraquídeo , Ácido Glutámico/líquido cefalorraquídeo , Hospitales Universitarios , Humanos , Pennsylvania , Síndrome del Ovario Poliquístico/sangre , Reproducibilidad de los Resultados , Testosterona/sangre , Adulto JovenRESUMEN
OBJECTIVE: To characterize pregnancy-associated deaths and examine the relationship between area of residence and pregnancy-associated deaths and pregnancy-related mortality ratios in Georgia from 2010 to 2012. METHODS: The cohort of pregnancy-associated deaths was reviewed and categorized as pregnancy-related or resulting from other medical conditions not related to pregnancy, suicide, drug toxicity, homicide, or motor vehicle accident. Georgia Online Analytical Statistical Information System data were used to calculate pregnancy-related mortality ratio by rural, nonrural, and metropolitan Atlanta area and by race. Causes of death and pregnancy-related mortality ratio were compared by area of residence and race using χ tests; a P value <.05 was considered significant. RESULTS: There were 262 pregnancy-associated deaths; 40.1% (n=105) were pregnancy-related. The 2010-2012 pregnancy-related mortality ratio was 26.5 per 100,000 live births and the pregnancy-related mortality ratio did not differ statistically among rural (27.1), nonrural (24.4), and metropolitan Atlanta (27.7) areas (P=.845). Most pregnancy-related deaths were the result of hemorrhage and cardiovascular factors. In aggregate, the pregnancy-related mortality ratio for black women was 49.5 compared with 14.3 for white women (P<.001). The gap in pregnancy-related mortality ratio between black and white women was highest for metropolitan Atlanta (51.6 compared with 12.4, P<.001), less in nonrural areas (50.3 compared with 12.0, P<.001), and comparable in rural areas (39.4 compared with 22.4, P=.281). CONCLUSION: Although the pregnancy-related mortality ratio was similar for rural, nonrural, and metropolitan Atlanta areas, it was significantly higher for black compared with white women living outside of rural areas.
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Causas de Muerte , Complicaciones del Embarazo , Adulto , Bases de Datos Factuales , Etnicidad/estadística & datos numéricos , Femenino , Georgia/epidemiología , Humanos , Mortalidad , Embarazo , Complicaciones del Embarazo/clasificación , Complicaciones del Embarazo/mortalidad , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricosRESUMEN
OBJECTIVE: This study aimed to assess risk of an adverse perinatal outcome for women with a low fetal fraction (LFF) result on noninvasive prenatal testing (NIPT). STUDY DESIGN: A retrospective cohort study whereby women with an LFF result were compared with women who had a sufficient fetal fraction (SFF) result on NIPT. Inclusion criteria were singleton pregnancies with quantification of fetal fraction and pregnancy outcome information. Primary outcome was a composite of any of the following: miscarriage, fetal demise, neonatal death, preterm birth, pregnancy-associated hypertensive disorder, placental abruption, and low birth weight. RESULTS: Three hundred forty-eight (94%) women had an SFF result, and 22 (6%) women had an LFF result. The mean gestational age at the time of NIPT was comparable for both groups. Women with an LFF result were more likely to be African American (86% vs 52%; p = 0.007) and have a higher body mass index (BMI) (mean BMI = 37 kg/m(2) vs BMI = 29 kg/m(2) ; p ≤ 0.001) than women with an SFF result. The composite outcome was significantly more common in the LFF group (59.1% vs 29%; p = 0.003). After adjusting for race and BMI, LFF remained independently associated with adverse perinatal outcome with adjusted odds ratio = 2.5 (95% confidence interval 1.01-6.2; p = 0.049). CONCLUSIONS: Women with an LFF result have an increased likelihood of an adverse pregnancy outcome.
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ADN/aislamiento & purificación , Feto/química , Técnicas Genéticas , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Diagnóstico Prenatal/métodos , Adolescente , Adulto , Sistema Libre de Células/química , Sistema Libre de Células/metabolismo , ADN/metabolismo , Femenino , Feto/metabolismo , Técnicas Genéticas/normas , Humanos , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/sangre , Estudios Retrospectivos , Manejo de Especímenes/normas , Adulto JovenRESUMEN
OBJECTIVES: The primary aim of this study was to compare the proportion of concomitant apical procedures in women undergoing hysterectomy for uterovaginal prolapse in 2001 and 2011. The secondary aim was to identify factors associated with receiving concomitant apical procedures in 2001 and 2011. METHODS: The Nationwide Inpatient Sample database was queried for women with a primary diagnosis of uterovaginal prolapse who underwent hysterectomy in 2001 and 2011. The study cohort was analyzed for demographics, clinical factors, and concomitant procedures. Factors potentially associated with receiving concomitant apical procedure were evaluated using univariable analysis and multivariate logistic regression. RESULTS: A total of 14,647 women were identified (5867 in 2001 and 8780 in 2011). In 2001, 26.9% women received a concomitant apical procedure, and this proportion increased to 48.2% in 2011 (odds ratio, 2.53; 95% confidence interval, 2.36-2.72; P < 0.0001). In 2001, the mean (SD) age was 53.8 (14.1) years compared with 56.8 (13.3) years in 2011. Although vaginal hysterectomy was most common in both years, a concomitant apical procedure was more likely to be performed with abdominal hysterectomy (P < 0.001). On multivariate analysis, age older than 50 years (P = 0.0001), abdominal route of hysterectomy (P < 0.0001), and undergoing hysterectomy at an academic teaching hospital (P < 0.0001) were independently associated with concomitant apical procedures in both 2001 and 2011. CONCLUSIONS: Although the proportion of concomitant apical repair was higher in 2011 compared with 2001, it is still low given the existing data demonstrating the importance of a concomitant apical procedure at the time of hysterectomy for uterovaginal prolapse.
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Histerectomía/métodos , Prolapso Uterino/cirugía , Adulto , Anciano , Femenino , Humanos , Histerectomía/estadística & datos numéricos , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Anti-Müllerian hormone (AMH) has potential local effects on ovarian function and endometrial tissue, including endometriosis, but its presence in peritoneal fluid is not fully understood. This is a cross-sectional study evaluating AMH in peritoneal fluid and plasma from women with endometriosis (N = 61) and from control women without endometriosis (N = 36). There was a significant correlation between AMH in plasma and peritoneal fluid from both patients with endometriosis (r(2) = .767 [P < .001]) and control participants (r(2) = .647 [P < .001]) less than 45 years of age. Anti-Müllerian hormone declined with women's increasing age in both plasma and peritoneal fluid in women with and without endometriosis. There were no differences in the plasma or peritoneal fluid AMH in women with endometriosis versus control women. The strong relationship between plasma and peritoneal fluid may allow plasma AMH to be a marker for peritoneal AMH in studies evaluating the local effects of AMH.
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Hormona Antimülleriana/sangre , Líquido Ascítico/química , Endometriosis/sangre , Adulto , Factores de Edad , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Regulación hacia Abajo , Endometriosis/diagnóstico , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate whether HIV infected pregnant women with concomitant sexually transmitted infection (STIs) are at increased risk of adverse perinatal and neonatal outcomes. METHODS: We conducted a cohort study of HIV positive women who delivered at an inner-city hospital in Atlanta, Georgia, from 2003 to 2013. Demographics, presence of concomitant STIs, prenatal care information, and maternal and neonatal outcomes were collected. The outcomes examined were the association of the presence of concomitant STIs on the risk of preterm birth (PTB), postpartum hemorrhage, chorioamnionitis, preeclampsia, intrauterine growth restriction, small for gestational age, low Apgar scores, and neonatal intensive care admission. Multiple logistic regression was performed to adjust for potential confounders. RESULTS: HIV positive pregnant women with concomitant STIs had an increased risk of spontaneous PTB (odds ratio (OR) 2.11, 95% confidence interval [CI] 1.12-3.97). After adjusting for a history of preterm birth, maternal age, and low CD4+ count at prenatal care entry the association between concomitant STIs and spontaneous PTB persisted (adjusted OR 1.96, 95% CI 1.01-3.78). CONCLUSIONS: HIV infected pregnant women with concomitant STIs relative to HIV positive pregnant women without a concomitant STI are at increased risk of spontaneous PTB.
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Infecciones por VIH/complicaciones , Complicaciones Infecciosas del Embarazo , Enfermedades de Transmisión Sexual/complicaciones , Adulto , Estudios de Cohortes , Femenino , Georgia , Humanos , Modelos Logísticos , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Atención Prenatal , Factores de RiesgoRESUMEN
OBJECTIVE: To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. DESIGN: Randomized controlled trial. SETTING: Clinical research center at an academic medical university. PATIENT(S): Seventeen women with FHA were randomized either to CBT or observation. INTERVENTION(S): CBT versus observation. MAIN OUTCOME MEASURE(S): Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) RESULT(S): Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. CONCLUSION(S): In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. CLINICAL TRIAL REGISTRATION NUMBER: NCT01674426.
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Amenorrea/terapia , Terapia Cognitivo-Conductual , Enfermedades Hipotalámicas/terapia , Sistemas Neurosecretores/metabolismo , Centros Médicos Académicos , Amenorrea/sangre , Amenorrea/diagnóstico , Amenorrea/fisiopatología , Amenorrea/psicología , Análisis de Varianza , Femenino , Humanos , Hidrocortisona/sangre , Enfermedades Hipotalámicas/sangre , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/fisiopatología , Enfermedades Hipotalámicas/psicología , Leptina/sangre , Sistemas Neurosecretores/fisiopatología , Pennsylvania , Recuperación de la Función , Tirotropina/sangre , Tiroxina/sangre , Factores de Tiempo , Resultado del Tratamiento , Triyodotironina/sangreRESUMEN
OBJECTIVE: Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. METHODS: In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. RESULTS: AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. CONCLUSIONS: These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.
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Lesiones Encefálicas/sangre , Lesiones Encefálicas/psicología , Trastornos del Conocimiento/sangre , Cognición , Estradiol/sangre , Hipogonadismo/sangre , Adolescente , Adulto , Anciano , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/fisiopatología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Estradiol/biosíntesis , Escala de Consecuencias de Glasgow , Humanos , Hipogonadismo/etiología , Hipogonadismo/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estrés Fisiológico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P < .05). The urine free cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation.
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Sistema Hipotálamo-Hipofisario/fisiopatología , Obesidad/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Absorciometría de Fotón , Adiposidad/fisiología , Adolescente , Antropometría , Área Bajo la Curva , Composición Corporal/fisiología , Índice de Masa Corporal , Mama/crecimiento & desarrollo , Niño , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Estudios Longitudinales , Menarquia , Sobrepeso/fisiopatología , Radioinmunoensayo , Factores SocioeconómicosRESUMEN
Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.
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Lesiones Encefálicas/sangre , Lesiones Encefálicas/diagnóstico , Citoprotección/fisiología , Hormonas Esteroides Gonadales/sangre , Enfermedad Aguda , Adulto , Lesiones Encefálicas/fisiopatología , Estudios de Cohortes , Femenino , Hormonas Esteroides Gonadales/biosíntesis , Hormonas Esteroides Gonadales/metabolismo , Humanos , Masculino , Pronóstico , Índice de Severidad de la Enfermedad , Estrés Fisiológico/fisiologíaRESUMEN
Sex steroids modulate brain function at all developmental stages of life. This article focuses on the role of sex steroids after menopause with the intent of addressing the question whether or to what extent sex steroids, particularly estrogenic agents, are neuroprotective for the aging brain of women. The rationale for delving into this complicated topic is that the information and perspective so acquired will aid physicians in counseling surgically and naturally menopausal women about their therapeutic options. Whereas we review and synthesize relevant data from monkey, other animal, cellular, and molecular studies, the emphasis is on human studies and reconciling the disparate evidence. Although the knowledge gaps are considerable, available evidence suggests that extended use of non-oral estradiol is a reasonable course of action if the woman to be treated has a relatively low risk for cardiovascular disease and venous thromboembolism or a high concern about developing dementia. It is important to emphasize that estradiol may negatively impact an already unhealthy individual and yet synergize other health-promoting behaviors such as good nutrition, exercise, and stress reduction in a relatively healthy individual.
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Encéfalo/efectos de los fármacos , Demencia/prevención & control , Terapia de Reemplazo de Estrógeno , Estrógenos/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Posmenopausia , Factores de Edad , Envejecimiento/metabolismo , Envejecimiento/patología , Inhibidores de la Aromatasa/farmacología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Cognición/efectos de los fármacos , Demencia/epidemiología , Demencia/metabolismo , Demencia/patología , Demencia/fisiopatología , Diagnóstico por Imagen , Esquema de Medicación , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/efectos adversos , Estrógenos/metabolismo , Medicina Basada en la Evidencia , Femenino , Humanos , Modelos Animales , Fármacos Neuroprotectores/efectos adversos , Medición de Riesgo , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Resultado del TratamientoRESUMEN
Girls with premature adrenarche (PA) are at risk for multiple problems related to exaggerated androgen synthesis. Whether PA carries a risk of psychopathology remains unknown. This study examined group differences in: (a) anthropometric and endocrine parameters, and (b) mood and behavior problems, in 6-8 year-old girls with PA (n = 40) compared to on-time adrenarche girls (n = 36). PA girls were taller (p < or =0.05) and heavier (p < or =0.01) than the on-time adrenarche girls but body mass index showed no difference. PA girls had significantly (p <0.05) higher adrenal androgen and testosterone concentrations but not cortisol or leptin. PA girls also had significantly more oppositional defiant disorder, and higher symptom counts reflecting anxiety, mood or disruptive behavior disorders. PA girls may be more vulnerable to psychopathology than on-time adrenarche girls. The challenge of future studies is to determine which PA girls are at risk for psychopathology and which are more resilient.
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Adrenarquia/psicología , Andrógenos/sangre , Pubertad Precoz/psicología , Testosterona/sangre , Adrenarquia/sangre , Adrenarquia/fisiología , Afecto/fisiología , Ansiedad/fisiopatología , Estatura/fisiología , Peso Corporal/fisiología , Estudios de Casos y Controles , Niño , Femenino , Humanos , Hidrocortisona/sangre , Leptina/sangre , Pubertad Precoz/sangre , Pubertad Precoz/fisiopatologíaRESUMEN
OBJECTIVE: To measure brain serotonin-1A (5HT1A) receptor binding potential (BP) in healthy and depressed postpartum women. DESIGN: 5HT1A receptor BP was measured with positron emission tomography by using [(11)C]WAY100635 a single time. Multivariate analysis of variance was used to determine depression effects on 5HT1A receptor BP in relevant brain regions. SETTING: An academic research environment. PATIENT(S): Seven postpartum healthy controls and nine postpartum depressed (PD) subjects with perinatal (antepartum or postpartum) depression onset. Of the nine PD subjects, five had unipolar depression, and four had bipolar disorder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 5HT1A receptor BP. RESULT(S): Age, time since delivery, and reproductive hormones did not differ between groups. Postsynaptic 5HT1A receptor binding in postpartum depression was reduced 20%-28% relative to controls, with most significant reductions in anterior cingulate and mesiotemporal cortices. CONCLUSION(S): Postsynaptic 5HT1A receptor binding is reduced in PD women by a similar magnitude as has been shown in other depression samples. The postpartum hormonal milieu and the large proportion of bipolar spectrum subjects in the PD group may have accentuated this finding in this small sample. Recognition of this neurobiological deficit in postpartum depression may be useful in the development of treatments and prevention strategies for this disabling disorder.
Asunto(s)
Química Encefálica , Depresión Posparto/diagnóstico por imagen , Sistema Límbico/diagnóstico por imagen , Tomografía de Emisión de Positrones , Receptor de Serotonina 5-HT1A/análisis , Adulto , Lactancia Materna , Radioisótopos de Carbono , Estudios de Casos y Controles , Depresión Posparto/metabolismo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Sistema Límbico/química , Hormona Luteinizante/sangre , Piperazinas/metabolismo , Tomografía de Emisión de Positrones/métodos , Progesterona/sangre , Prolactina/sangre , Unión Proteica , Escalas de Valoración Psiquiátrica , Piridinas/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Antagonistas de la Serotonina/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Technical hurdles limit the characterization of key hormonal rhythms. Frequent sampling increases detection of changes in magnitude or circadian and ultradian patterns, but limits feasibility for clinical or research settings. These caveats are particularly pertinent for cortisol, a hormone that displays a prominent circadian rhythm and whose magnitude is tightly regulated in the absence of biobehavioural challenge. Ideally, one would like to obtain samples non-invasively from a matrix of interest at frequent intervals. While many investigations have reported a high correlation between serum and salivary cortisol assays, the degree to which salivary cortisol reflects the circadian patterns of circulating cortisol concentrations has not been established across a 24 h period. METHODS: We obtained hourly serum and salivary samples over a 24 h period in nine adults in an inpatient setting. The circadian patterns for serum and salivary cortisol were analysed by harmonic regression. RESULTS: For all but two subjects (both on oral contraceptives), the salivary cortisol concentration was synchronous with the serum concentration, indicating that the salivary assay could be substituted for the serum assay to assess circulating rhythmicity across the 24 h time frame. CONCLUSIONS: This statistical model has distinct improvement over the correlational approach of examining serum and saliva cortisol relationships. Saliva cortisol appears to represent serum cortisol across the 24 h period, except for those on oral contraceptives.