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TRIAL DESIGN: SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies conducted in the United States, as well as the United Kingdom and Germany (SPARTAN only). Individuals with migraine were randomized to receive oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo within 4 hours of onset of a migraine attack. The aim of this analysis was to characterize dizziness reported with lasmiditan treatment. METHODS: Data from SAMURAI and SPARTAN were pooled for the current post hoc analyses. Onset time and duration of dizziness were analyzed using descriptive statistics. Subgroup analyses based on presence/absence of dizziness were performed for the endpoints of interference with daily activity, patient global impression of change (PGIC), pain at 2 hours, and most bothersome symptom (MBS) at 2 hours based on adverse events occurring within 2 hours of taking study drug. RESULTS: Dizziness incidence was as follows: Placebo (N = 1262), 2.9% (0.1% severe); lasmiditan 50 mg (N = 654), 8.6% (0.3% severe); lasmiditan 100 mg (N = 1265), 14.9% (0.7% severe); and lasmiditan 200 mg (N = 1258), 16.8% (1.4% severe). Among participants who received lasmiditan as their first dose, risk factors for dizziness were higher lasmiditan dosage, being non-Hispanic/Latino, mild or moderate severity of migraine attack, and lower body mass index. The median time to onset of dizziness was generally 30-40 minutes, and the median duration was 1.5-2 hours. The presence of dizziness did not appear to have a negative influence on lasmiditan's effect on daily activity, PGIC, freedom from pain, or MBS. Overall, 21 participants experienced vertigo: Lasmiditan 50 mg, n = 2 (0.3%); 100 mg, n = 11 (0.9%); 200 mg, n = 7 (0.6%); and placebo, n = 1 (<0.1%). CONCLUSION: The incidence of dizziness with lasmiditan increased with dose. Dizziness was generally mild or moderate in severity and of quick onset and short duration. The presence of dizziness did not influence drug efficacy.
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Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Mareo/inducido químicamente , Trastornos Migrañosos/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Vértigo/inducido químicamente , Enfermedad Aguda , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: This project explores a new model of care that enhances survivorship care planning and promotes health for men with localized prostate cancer transitioning to posttreatment self-management. Survivorship care planning is important for patients with prostate cancer because of its high incidence rate in the United States, the frequent occurrence of treatment-related side effects, and reduced quality of life (QOL) for both men and their partners. A key component of comprehensive survivorship care planning is survivorship care plans (SCPs), documents that summarize cancer diagnosis, treatment, and plans for follow-up care. However, research concerning the effectiveness of SCPs on patient outcomes or health service use has thus far been inconclusive. SCPs that are tailored to individual patients' needs for information and care may improve effectiveness. OBJECTIVE: This study aims to examine the feasibility of an enhanced survivorship care plan (ESCP) that integrates a symptom self-management mHealth program called Prostate Cancer Education and Resources for Couples (PERC) into the existing standardized SCP. The specific aims are to (1) examine the feasibility of delivering ESCPs and (2) to estimate the magnitude of benefit of ESCPs. METHODS: We will use a two-group randomized controlled pretest-posttest design and collect data at baseline (T1) and 4 months later (T2) among 50 patients completing initial treatment for localized prostate cancer and their partners. First, we will assess the feasibility of ESCP by recruitment, enrollment, and retention rates; program satisfaction with the ESCP; and perceived ease of use of the ESCP. To achieve the secondary aim, we will compare the ESCP users with the standardized SCP users and assess their primary outcomes of QOL (overall, physical, emotional, and social QOL); secondary outcomes (reduction in negative appraisals and improvement in self-efficacy, social support, and health behaviors to manage symptoms); and number of visits to posttreatment care services between T1 and T2. We will assess the primary and secondary outcomes using measurements with sound psychometrical properties. We will use a qualitative and quantitative mixed methods approach to achieve the research aims. RESULTS: This project is ongoing and will be completed by the end of 2018. CONCLUSIONS: The results from this study will help design a definitive randomized trial to test the efficacy of the ESCPs, a potentially scalable program, to enhance supportive care for prostate cancer patients and their families.
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BACKGROUND: Immunization rates for children and adults are rising, but coverage levels have not reached optimal goals. As a result, vaccine-preventable diseases still occur. In an era of increasing complexity of immunization schedules, rising expectations about the performance of primary care, and large demands on primary care providers, it is important to understand and promote interventions that work in primary care settings to increase immunization coverage. One common theme across immunization programs in many nations involves the challenge of implementing a population-based approach and identifying all eligible recipients, for example the children who should receive the measles vaccine. However, this issue is gradually being addressed through the availability of immunization registries and electronic health records. A second common theme is identifying the best strategies to promote high vaccination rates. Three types of strategies have been studied: (1) patient-oriented interventions, such as patient reminder or recall, (2) provider interventions, and (3) system interventions, such as school laws. One of the most prominent intervention strategies, and perhaps best studied, involves patient reminder or recall systems. This is an update of a previously published review. OBJECTIVES: To evaluate and compare the effectiveness of various types of patient reminder and recall interventions to improve receipt of immunizations. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2017. We also searched grey literature and trial registers to January 2017. SELECTION CRITERIA: We included randomized trials, controlled before and after studies, and interrupted time series evaluating immunization-focused patient reminder or recall interventions in children, adolescents, and adults who receive immunizations in any setting. We included no-intervention control groups, standard practice activities that did not include immunization patient reminder or recall, media-based activities aimed at promoting immunizations, or simple practice-based awareness campaigns. We included receipt of any immunizations as eligible outcome measures, excluding special travel immunizations. We excluded patients who were hospitalized for the duration of the study period. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group. We present results for individual studies as relative rates using risk ratios, and risk differences for randomized trials, and as absolute changes in percentage points for controlled before-after studies. We present pooled results for randomized trials using the random-effects model. MAIN RESULTS: The 75 included studies involved child, adolescent, and adult participants in outpatient, community-based, primary care, and other settings in 10 countries.Patient reminder or recall interventions, including telephone and autodialer calls, letters, postcards, text messages, combination of mail or telephone, or a combination of patient reminder or recall with outreach, probably improve the proportion of participants who receive immunization (risk ratio (RR) of 1.28, 95% confidence interval (CI) 1.23 to 1.35; risk difference of 8%) based on moderate certainty evidence from 55 studies with 138,625 participants.Three types of single-method reminders improve receipt of immunizations based on high certainty evidence: the use of postcards (RR 1.18, 95% CI 1.08 to 1.30; eight studies; 27,734 participants), text messages (RR 1.29, 95% CI 1.15 to 1.44; six studies; 7772 participants), and autodialer (RR 1.17, 95% CI 1.03 to 1.32; five studies; 11,947 participants). Two types of single-method reminders probably improve receipt of immunizations based on moderate certainty evidence: the use of telephone calls (RR 1.75, 95% CI 1.20 to 2.54; seven studies; 9120 participants) and letters to patients (RR 1.29, 95% CI 1.21 to 1.38; 27 studies; 81,100 participants).Based on high certainty evidence, reminders improve receipt of immunizations for childhood (RR 1.22, 95% CI 1.15 to 1.29; risk difference of 8%; 23 studies; 31,099 participants) and adolescent vaccinations (RR 1.29, 95% CI 1.17 to 1.42; risk difference of 7%; 10 studies; 30,868 participants). Reminders probably improve receipt of vaccinations for childhood influenza (RR 1.51, 95% CI 1.14 to 1.99; risk difference of 22%; five studies; 9265 participants) and adult influenza (RR 1.29, 95% CI 1.17 to 1.43; risk difference of 9%; 15 studies; 59,328 participants) based on moderate certainty evidence. They may improve receipt of vaccinations for adult pneumococcus, tetanus, hepatitis B, and other non-influenza vaccinations based on low certainty evidence although the confidence interval includes no effect of these interventions (RR 2.08, 95% CI 0.91 to 4.78; four studies; 8065 participants). AUTHORS' CONCLUSIONS: Patient reminder and recall systems, in primary care settings, are likely to be effective at improving the proportion of the target population who receive immunizations.
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Inmunización/estadística & datos numéricos , Sistemas Recordatorios , Adolescente , Adulto , Niño , Correspondencia como Asunto , Humanos , Programas de Inmunización/organización & administración , Ensayos Clínicos Controlados Aleatorios como Asunto , Sistemas Recordatorios/estadística & datos numéricos , Teléfono/estadística & datos numéricos , Envío de Mensajes de Texto/estadística & datos numéricosRESUMEN
In studies that compare several diagnostic groups, subjects can be measured on certain features and classification trees can be used to identify which of them best characterize the differences among groups. However, subjects may also be measured on additional covariates whose ability to characterize group differences is not meaningful or of interest, but may still have an impact on the examined features. Therefore, it is important to adjust for the effects of covariates on these features. We present a new semi-parametric approach to adjust for covariate effects when constructing classification trees based on the features of interest that is readily implementable. An application is given for postmortem brain tissue data to compare the neurobiological characteristics of subjects with schizophrenia to those of normal controls. We also evaluate the performance of our approach using a simulation study.
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Investigación Biomédica , Bioestadística , Clasificación , Interpretación Estadística de Datos , Modelos Estadísticos , Investigación Biomédica/métodos , Bioestadística/métodos , HumanosRESUMEN
Lifestyle interventions targeting gestational weight gain (GWG) report varying degrees of success. To better understand factors influencing efficacy, we reviewed randomized trials specifically among obese and overweight pregnant women. METHODS: We conducted a systematic review and a meta-analysis of 32 studies with a pooled population of 5,869 overweight or obese pregnant women. Random effects models were fit to compute the weighted mean difference (WMD) in GWG between groups across studies. Subgroup analyses were conducted to compare intervention efficacy in overweight vs. obese pregnant women, and interventions delivered by prenatal care providers (PCPs) vs. non-PCPs during pregnancy. Moderator analyses ensured. RESULTS: Nine (28%) of 32 studies reported significant reductions in GWG in response to intervention. Of these, six (66%) of nine were delivered by PCPs. Overall, the WMD in GWG was -1.71 (95% confidence interval [CI]: -2.55, -0.86) kg. However, interventions delivered by PCPs yielded a significantly greater reduction in GWG compared to interventions delivered by non-PCPs (WMD = -3.88 kg; 95% CI: -7.01, -0.75 vs. -0.80 kg; 95% CI: -1.32, -0.28; p for difference = 0.005). CONCLUSION: When PCPs counsel nutrition and physical activity, obese and overweight pregnant women have greater success meeting GWG targets and may be more motivated to modify their behaviour than with other modes of intervention deliveries.
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Ejercicio Físico , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/prevención & control , Sobrepeso/prevención & control , Complicaciones del Embarazo/prevención & control , Mujeres Embarazadas , Atención Prenatal/métodos , Dieta , Femenino , Humanos , Obesidad/complicaciones , Sobrepeso/complicaciones , Embarazo , Mujeres Embarazadas/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Aumento de PesoRESUMEN
OBJECTIVE: To examine health departments' (HD) capacity to adapt and implement an intervention to prevent excessive gestational weight gain. DESIGN AND SAMPLE: Seventy-seven stakeholders (nurses, nutritionists, social workers, health educators, health directors, and multilingual service providers) in nine HDs participated. A descriptive mixed methods approach was used to collect data at workshops held onsite to introduce the evidence-based intervention (EBI) and discuss its adaptation. MEASURES: A survey was administered to assess the intervention's fit with the HDs context. Generalized logit mixed models were used to analyze the survey data. The discussions of adaptation were audiotaped and thematically analyzed to identify factors influencing implementation. RESULTS: The majority of stakeholders desired to participate in the training portion of the EBI, but they were reluctant to adopt it, and noted a lack of adequate resources. From the audiotaped narratives, three themes emerged: (1) Patient needs and resources, (2) Perception about adaptability of the EBI, and (3) The complexity of the EBI for pregnant populations. CONCLUSION: Although the EBI was effective for low-income nonpregnant populations in southeastern regions, pregnancy and complex antenatal services make this intervention unrealistic to be adapted as a part of prenatal care at HDs.
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Agencias Gubernamentales , Obesidad/prevención & control , Pobreza , Complicaciones del Embarazo/prevención & control , Aumento de Peso , Adulto , Medicina Basada en la Evidencia , Femenino , Promoción de la Salud , Humanos , Embarazo , Estados UnidosRESUMEN
AIMS/METHODS: We studied 735 patients who activated "911" for chest pain and/or anginal equivalent symptoms and received 12-lead ECG monitoring with specialized ischemia monitoring software in the ambulance. Prehospital electrocardiograms (PH ECG) were analyzed to determine the proportion of patients who present with completely normal PH ECG findings (absence of ischemia/infarction, arrhythmia, or any other abnormality) and to compare outcomes among patients with and without any PH ECG abnormality. RESULTS: Of 735 patients (mean age 70.5, 52.4% male), 68 (9.3%) patients had completely normal PH ECG findings. They experienced significantly less adverse hospital outcomes (12% vs 37%), length of stay (1.19 vs 3.86 days), and long-term mortality (9% vs 28%) than those with any PH ECG abnormality (p<.05). CONCLUSION: Normal PH ECG findings are associated with better short and long-term outcomes in ambulance patients with ischemic symptoms. These findings may enhance early triage and risk stratification in emergency cardiac care.
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Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Electrocardiografía/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Sobrevivientes/estadística & datos numéricos , Anciano , California/epidemiología , Electrocardiografía/métodos , Servicios Médicos de Urgencia/métodos , Femenino , Humanos , Incidencia , Masculino , Pronóstico , Valores de Referencia , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Tasa de Supervivencia , Triaje/métodos , Triaje/estadística & datos numéricosRESUMEN
Despite the relatively high accuracy of the naïve Bayes (NB) classifier, there may be several instances where it is not optimal, i.e. does not have the same classification performance as the Bayes classifier utilizing the joint distribution of the examined attributes. However, the Bayes classifier can be computationally intractable due to its required knowledge of the joint distribution. Therefore, we introduce a "pairwise naïve" Bayes (PNB) classifier that incorporates all pairwise relationships among the examined attributes, but does not require specification of the joint distribution. In this paper, we first describe the necessary and sufficient conditions under which the PNB classifier is optimal. We then discuss sufficient conditions for which the PNB classifier, and not NB, is optimal for normal attributes. Through simulation and actual studies, we evaluate the performance of our proposed classifier relative to the Bayes and NB classifiers, along with the HNB, AODE, LBR and TAN classifiers, using normal density and empirical estimation methods. Our applications show that the PNB classifier using normal density estimation yields the highest accuracy for data sets containing continuous attributes. We conclude that it offers a useful compromise between the Bayes and NB classifiers.
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Schizophrenia is associated with auditory processing impairments that could arise as a result of primary auditory cortex excitatory circuit pathology. We have previously reported a deficit in dendritic spine density in deep layer 3 of primary auditory cortex in subjects with schizophrenia. As boutons and spines can be structurally and functionally co-regulated, we asked whether the densities of intracortical excitatory or thalamocortical presynaptic boutons are also reduced. We studied 2 cohorts of subjects with schizophrenia and matched controls, comprising 27 subject pairs, and assessed the density, number, and within-bouton vesicular glutamate transporter (VGluT) protein level of intracortical excitatory (VGluT1-immunoreactive) and thalamocortical (VGluT2-immunoreactive) boutons in deep layer 3 of primary auditory cortex using quantitative confocal microscopy and stereologic sampling methods. We found that VGluT1- and VGluT2-immunoreactive puncta densities and numbers were not altered in deep layer 3 of primary auditory cortex of subjects with schizophrenia. Our results indicate that reduced dendritic spine density in primary auditory cortex of subjects with schizophrenia is not matched by a corresponding reduction in excitatory bouton density. This suggests excitatory boutons in primary auditory cortex in schizophrenia may synapse with structures other than spines, such as dendritic shafts, with greater frequency. The discrepancy between dendritic spine reduction and excitatory bouton preservation may contribute to functional impairments of the primary auditory cortex in subjects with schizophrenia.
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Corteza Auditiva/patología , Terminales Presinápticos/patología , Esquizofrenia/patología , Tálamo/patología , Adulto , Animales , Corteza Auditiva/metabolismo , Corteza Auditiva/fisiopatología , Estudios de Casos y Controles , Estudios de Cohortes , Dendritas/diagnóstico por imagen , Femenino , Humanos , Modelos Lineales , Macaca fascicularis , Masculino , Persona de Mediana Edad , Terminales Presinápticos/metabolismo , Escalas de Valoración Psiquiátrica , Cintigrafía , Sinaptofisina/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
In studies that compare several diagnostic or treatment groups, subjects may not only be measured on a certain set of feature variables, but also be matched on a number of demographic characteristics and measured on additional covariates. Linear discriminant analysis (LDA) is sometimes used to identify which feature variables best discriminate among groups, while accounting for the dependencies among the feature variables. We present a new approach to LDA for multivariate normal data that accounts for the subject matching used in a particular study design, as well as covariates not used in the matching. Applications are given for post-mortem tissue data with the aim of comparing neurobiological characteristics of subjects with schizophrenia with those of normal controls, and for a post-mortem tissue primate study comparing brain biomarker measurements across three treatment groups. We also investigate the performance of our approach using a simulation study.
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Interpretación Estadística de Datos , Análisis Discriminante , Animales , Antipsicóticos/farmacología , Biomarcadores , Encéfalo/patología , Simulación por Computador , Femenino , Humanos , Macaca , Masculino , Proyectos de Investigación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patologíaRESUMEN
BACKGROUND: Schizophrenia is associated with perceptual and physiological auditory processing impairments that may result from primary auditory cortex excitatory and inhibitory circuit pathology. High-frequency oscillations are important for auditory function and are often reported to be disrupted in schizophrenia. These oscillations may, in part, depend on upregulation of gamma-aminobutyric acid synthesis by glutamate decarboxylase 65 (GAD65) in response to high interneuron firing rates. It is not known whether levels of GAD65 protein or GAD65-expressing boutons are altered in schizophrenia. METHODS: We studied two cohorts of subjects with schizophrenia and matched control subjects, comprising 27 pairs of subjects. Relative fluorescence intensity, density, volume, and number of GAD65-immunoreactive boutons in primary auditory cortex were measured using quantitative confocal microscopy and stereologic sampling methods. Bouton fluorescence intensities were used to compare the relative expression of GAD65 protein within boutons between diagnostic groups. Additionally, we assessed the correlation between previously measured dendritic spine densities and GAD65-immunoreactive bouton fluorescence intensities. RESULTS: GAD65-immunoreactive bouton fluorescence intensity was reduced by 40% in subjects with schizophrenia and was correlated with previously measured reduced spine density. The reduction was greater in subjects who were not living independently at time of death. In contrast, GAD65-immunoreactive bouton density and number were not altered in deep layer 3 of primary auditory cortex of subjects with schizophrenia. CONCLUSIONS: Decreased expression of GAD65 protein within inhibitory boutons could contribute to auditory impairments in schizophrenia. The correlated reductions in dendritic spines and GAD65 protein suggest a relationship between inhibitory and excitatory synapse pathology in primary auditory cortex.
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Corteza Auditiva/enzimología , Glutamato Descarboxilasa/metabolismo , Terminales Presinápticos/enzimología , Esquizofrenia/enzimología , Adulto , Anciano , Animales , Corteza Auditiva/efectos de los fármacos , Estudios de Casos y Controles , Espinas Dendríticas/metabolismo , Femenino , Haloperidol/farmacología , Humanos , Macaca , Masculino , Persona de Mediana Edad , Imagen Molecular/métodosRESUMEN
OBJECTIVE: Cognitive deficits in schizophrenia are associated with altered activity of the dorsolateral prefrontal cortex, which has been attributed to lower expression of the 67 kDa isoform of glutamic acid decarboxylase (GAD67), the major γ-aminobutyric acid (GABA)-synthesizing enzyme. However, little is known about the relationship of prefrontal GAD67 mRNA levels and illness severity, translation of the transcript into protein, and protein levels in axon terminals, the key site of GABA production and function. METHOD: Quantitative polymerase chain reaction was used to measure GAD67 mRNA levels in postmortem specimens of dorsolateral prefrontal cortex from subjects with schizophrenia and matched comparison subjects with no known history of psychiatric or neurological disorders (N=42 pairs). In a subset of this cohort in which potential confounds of protein measures were controlled (N=19 pairs), Western blotting was used to quantify tissue levels of GAD67 protein in tissue. In five of these pairs, multilabel confocal immunofluorescence was used to quantify GAD67 protein levels in the axon terminals of parvalbumin-containing GABA neurons, which are known to have low levels of GAD67 mRNA in schizophrenia. RESULTS: GAD67 mRNA levels were significantly lower in schizophrenia subjects (by 15%), but transcript levels were not associated with predictors or measures of illness severity or chronicity. In schizophrenia subjects, GAD67 protein levels were significantly lower in total gray matter (by 10%) and in parvalbumin axon terminals (by 49%). CONCLUSIONS: The findings that lower GAD67 mRNA expression is common in schizophrenia, that it is not a consequence of having the illness, and that it leads to less translation of the protein, especially in the axon terminals of parvalbumin-containing neurons, support the hypothesis that lower GABA synthesis in parvalbumin neurons contributes to dorsolateral prefrontal cortex dysfunction and impaired cognition in schizophrenia.
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Trastornos del Conocimiento/genética , Glutamato Descarboxilasa/genética , Neuronas/metabolismo , Parvalbúminas/metabolismo , Corteza Prefrontal/enzimología , Esquizofrenia/genética , Ácido gamma-Aminobutírico/metabolismo , Adulto , Western Blotting , Trastornos del Conocimiento/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Neuronas/patología , Corteza Prefrontal/patología , Terminales Presinápticos , ARN Mensajero/genética , Valores de Referencia , Esquizofrenia/patologíaRESUMEN
Pharmacological blockade of norepinephrine (NE) reuptake is clinically effective in treating several mental disorders. Drugs that bind to the NE transporter (NET) alter both protein levels and activity of NET and also the catecholamine synthetic enzyme tyrosine hydroxylase (TH). We examined the rat prefrontal cortex (PFC) by electron microscopy to determine whether the density and subcellular distribution of immunolabelling for NET and co-localization of NET with TH within individual NE axons were altered by chronic treatment with the selective NE uptake inhibitor desipramine (DMI). Following DMI treatment (21 d, 15 mg/kg.d), NET-immunoreactive (ir) axons were significantly less likely to co-localize TH. This finding is consistent with reports of reduced TH levels and activity in the locus coeruleus after chronic DMI and indicates a reduction of NE synthetic capacity in the PFC. Measures of NET expression and membrane localization, including the number of NET-ir profiles per tissue area sampled, the number of gold particles per NET-ir profile area, and the proportion of gold particles associated with the plasma membrane, were similar in DMI- and vehicle-treated rats. These findings were verified using two different antibodies directed against distinct epitopes of the NET protein. The results suggest that chronic DMI treatment does not reduce NET expression within individual NE axons in vivo or induce an overall translocation of NET protein away from the plasma membrane in the PFC as measured by ultrastructural immunogold labelling. Our findings encourage consideration of possible post-translational mechanisms for regulating NET activity in antidepressant-induced modulation of NE clearance.