Blinded, multi-center validation of EEG and rating scales in identifying ADHD within a clinical sample.

Previous validation studies of attention deficit/hyperactivity disorder (ADHD) assessment by rating scales or EEG have provided Class-IV evidence per standards of the American Academy of Neurology. To investigate clinical applications, we collected Class-I evidence, namely from a blinded, prospective, multi-center study of a representative clinical sample categorized with a clinical standard. Participating males (101) and females (58) aged 6 to 18 had presented to one of four psychiatric and pediatric clinics because of the suspected presence of attention and behavior problems. DSM-IV diagnosis was performed by clinicians assisted with a semi-structured clinical interview. EEG (theta/beta ratio) and ratings scales (Conners Rating Scales-Revised and ADHD Rating Scales-IV) were collected separately in a blinded protocol. ADHD prevalence in the clinical sample was 61%, whereas the remainder had other childhood/adolescent disorders or no diagnosis. Comorbidities were observed in 66% of ADHD patients and included mood, anxiety, disruptive, and learning disorders at rates similar to previous findings. EEG identified ADHD with 87% sensitivity and 94% specificity. Rating scales provided sensitivity of 38-79% and specificity of 13-61%. While parent or teacher identification of ADHD by rating scales was reduced in accuracy when applied to a diverse clinical sample, theta/beta ratio changes remained consistent with the clinician's ADHD diagnosis. Because theta/beta ratio changes do not identify comorbidities or alternative diagnoses, the results do not support the use of EEG as a stand-alone diagnostic and should be limited to the interpretation that EEG may complement a clinical evaluation for ADHD.

Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study.

BACKGROUND: The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. OBJECTIVE: The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. METHODS: This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. RESULTS: Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. CONCLUSION: These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study.

Comparison of a standard psychiatric evaluation to rating scales and EEG in the differential diagnosis of attention-deficit/hyperactivity disorder.

The objective was to investigate the effectiveness of rating scales and electroencephalography (EEG) in detecting the presence of attention-deficit/hyperactivity disorder (ADHD) within a diverse clinical sample. A standard psychiatric evaluation was used to assess 26 children/adolescents who presented to a clinic because a parent suspected the presence of ADHD. EEG data was collected in a blinded protocol, and rating scales were collected as well. Although all subjects had presented with ADHD-like symptoms, only 62% were diagnosed with ADHD, while the remaining 38% had other disorders or no diagnosis. Rating scales readily classified inattentive, impulsive, and/or hyperactive symptoms as being due to ADHD, regardless of the actual underlying disorder, leading to a sensitivity of 81% and a specificity of 22%. Previous studies have observed that there is an EEG marker that identifies ADHD vs. controls, and this marker was present in 15 out of 16 of the ADHD subjects (sensitivity=94%) and in none of the subjects with ADHD-like symptoms due to other disorders (specificity=100%). In the detection of ADHD in a diverse clinical sample, rating scales and EEG were both sensitive markers, whereas only EEG was specific. These results may have important implications to ADHD differential diagnosis.

Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.

This double-blind study examined efficacy and safety of atomoxetine (ATX; < or =1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, > or =1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, > or = 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

An open-label study of olanzapine in children and adolescents with schizophrenia.

The purpose of this open-label study was to evaluate the use of olanzapine in the treatment of children and adolescents with schizophrenia. Sixteen children who were 8-17 years of age and met DSM-IV criteria for schizophrenia were admitted into a 10-week, open-label, optimizing dose study of olanzapine. The Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression (CGI)-Severity/Improvement scales were used to assess improvement during the study. Of the 16 subjects who completed the study, 12 demonstrated significant improvement on end of treatment BPRS, CGI, and PANSS scores compared with baseline. Male subjects showed greater improvement and also gained more weight. Weight gain occurred in all but 2 subjects. Weight gain was significant, with patients averaging a gain of about 6.2 kg during the 6-week course of the study. Two of the subjects experienced extrapyramidal symptoms. The average dose of olanzapine for all subjects was 0.17 mg/kg.

Review of clinical validation of ADHD behavior rating scales.

The purpose of this review is to assess the range of overall accuracies for Attention Deficit/Hyperactivity Disorder (ADHD) behavior rating scales evaluated in clinical validation studies. Studies were characterized according to the evidence standards of the American Academy of Neurology (AAN). Studies were excluded due to major design problems such as overfitting by discriminant analysis. The 13 included evaluations of rating scales revealed overall accuracy in the range of 59%-79% with a pooled mean of 69% (+/-7%, standard deviation) and a pooled sample size of 2228 subjects from nine studies. While some of the excluded studies demonstrated higher overall accuracies (>79%), these studies were observed to have factors in experimen tal design and statistics that are known to unduly inflate accuracy. We recommend further research following the full AAN standards, namely well-designed, blinded, pro spective studies of rating scales applied to clinically representative samples evaluated with a clinical standard.

Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms.

OBJECTIVE: Symptoms of depression and anxiety are commonly comorbid with attention-deficit/hyperactivity disorder (ADHD). The authors assessed the safety and effectiveness of atomoxetine monotherapy compared with combined atomoxetine/fluoxetine therapy in a population of children and adolescents with ADHD and concurrent symptoms of depression or anxiety. METHOD: Patients were randomized to treatment with fluoxetine (n = 127) or placebo (n = 46) under double-blind conditions for 8 weeks, with concomitant atomoxetine use the last 5 weeks. RESULTS: At end point, reductions in ADHD, depressive, and anxiety symptoms were marked for both treatment groups (p < .001 for the relevant scale in each symptom cluster). Some differences between treatment groups for depressive symptoms were significant, but the magnitudes of the differences were small and likely of limited clinical importance. Completion rates for the two groups were similar, as were discontinuation rates for adverse events. The combination group had greater increases in blood pressure and pulse than did the monotherapy group. CONCLUSIONS: In pediatric patients with ADHD and comorbid symptoms of depression or anxiety, atomoxetine monotherapy appears to be effective for treating ADHD. Anxiety and depressive symptoms also improved, but the absence of a placebo-only arm does not allow us to conclude that these effects are specifically the result of treatment with atomoxetine. Combined atomoxetine/fluoxetine therapy was well tolerated.

Cardiovascular effects of atomoxetine in children, adolescents, and adults.

BACKGROUND: Atomoxetine is a highly specific presynaptic inhibitor of the noradrenaline (norepinephrine) transporter that was recently approved in the US for the treatment of patients with attention-deficit/hyperactivity disorder (ADHD). Adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, or cardiac rhythm have been associated with several noradrenergic medications. OBJECTIVE: To further elucidate the magnitude and impact of blood pressure and pulse elevations in patients taking atomoxetine. STUDY DESIGN: Short-term cardiovascular safety in children, adolescents, and adults with ADHD was assessed in five randomised, double-blind trials (duration up to 10 weeks) with atomoxetine (n = 612) or placebo (n = 474). Long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients who entered an open-label extension or a blinded continuation following short-term treatment. METHODS: Adverse events, blood pressure, sitting pulse, and electrocardiograms (ECGs) were collected throughout the trials. QT intervals were corrected for heart rate by a data-specific correction factor (QTcD; derived from baseline ECGs) as well as standard methods. RESULTS: Atomoxetine treatment was associated with small but statistically significant increases in mean systolic blood pressure in adults and diastolic blood pressure in children and adolescents. Mean pulse rate increased for all atomoxetine treatment groups. The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation. There was no significant difference between atomoxetine and placebo treatment groups in change in QTcD interval for all study populations. Palpitations in the adult patient population were the only significant cardiovascular adverse event (p = 0.037) occurring more frequently in the atomoxetine treatment group (3.7%) than in the placebo group (0.8%). Discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group. CONCLUSION: While atomoxetine has noradrenergic activity, increases in pulse and blood pressure were small and of little, if any, clinical significance. Atomoxetine was not associated with QT interval prolongation. Cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies.

Obstrucción intestinal ileal por endometriosis: Descripción de una causa infrecuente de obstrucción intestinal en pacientes jóvenes / Intestinal ileal obstruction by endometriosis: Description of a rare cause of intestinal obstruction in young patients

La endometriosis es una enfermedad frecuente en mujeres en etapa reproductiva (premenopáusicas), pero el compromiso gastrointestinal por endometriosis es raro, y aún más extraño es la presentación como obstrucción intestinal. Presentamos dos casos clínicos de mujeres en edad reproductiva que consultan por dolor abdominal, y clínica compatible con obstrucción intestinal alta, y documentación histopatológica de compromiso por endometriosis.

Endometriosis is a common disease in women of reproductive age (premenopausal), but gastrointestinal involvement by endometriosis is rare, and its presentation as intestinal obstruction is even stranger. 2 cases of women of reproductive age presenting with abdominal pain and compatible clinical picture of high intestinal obstruction and histopathological documentation of endometriosis, are presented.

Once-daily atomoxetine for treating pediatric attention-deficit/hyperactivity disorder: comparison of morning and evening dosing.

In this 3-arm, randomized, double-blind trial, once-daily morning-dosed atomoxetine, evening-dosed atomoxetine, and placebo were compared for treating pediatric attention-deficit/hyperactivity disorder (ADHD). Patients received morning atomoxetine/evening placebo (n = 102), morning placebo/evening atomoxetine (n = 93), or morning placebo/evening placebo (n = 93) for about 6 weeks. Core symptom efficacy was measured at weeks 0, 1, 3, and 6. Parent assessments of the child's home behaviors in the evening and early morning were collected daily during the first 2 weeks of treatment. Morning-dosed and evening-dosed atomoxetine significantly decreased core ADHD symptoms relative to placebo and produced symptom improvements that were measured up to 24 hours later. Morning dosing was superior to evening dosing on some efficacy measures. Evening dosing showed greater tolerability with significantly more patients receiving morning atomoxetine reporting at least 1 adverse event than those receiving evening atomoxetine.

Fluoxetine monotherapy in attention-deficit/hyperactivity disorder and comorbid non-bipolar mood disorders in children and adolescents.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for ADHD and comorbid non-bipolar mood disorders in a prospective, 6-12-week open-label, study of fluoxetine monotherapy. Fluoxetine was associated with significant decreases in the severity of depressive symptoms, and also, associated with significant decreases on subscales of inattention/overactivity and aggression/defiant symptoms-47% of participants were much or very much improved without observed adverse effects.

Transcranial magnetic stimulation in persons younger than the age of 18.

OBJECTIVES: To review the use of transcranial magnetic stimulation (single-pulse TMS, paired TMS, and repetitive TMS [rTMS]) in persons younger than the age of 18 years. I discuss the technical differences, as well as the diagnostic, therapeutic, and psychiatric uses of TMS/rTMS in this age group. METHODS: I evaluated English-language studies from 1993 to August 2004 on nonconvulsive single-pulse, paired, and rTMS that supported a possible role for the use of TMS in persons younger than 18. Articles reviewed were retrieved from the MEDLINE database and Clinical Scientific index. RESULTS: The 48 studies reviewed involved a total of 1034 children ages 2 weeks to 18 years; 35 of the studies used single-pulse TMS (980 children), 3 studies used paired TMS (20 children), and 7 studies used rTMS (34 children). Three studies used both single and rTMS. However, the number of subjects involved was not reported. CONCLUSIONS: Single-pulse TMS, paired TMS, and rTMS in persons younger than 18 has been used to examine the maturation/activity of the neurons of various central nervous system tracts, plasticity of neurons in epilepsy, other aspects of epilepsy, multiple sclerosis, myoclonus, transcallosal inhibition, and motor cortex functioning with no reported seizure risk. rTMS has been applied to psychiatric disorders such as ADHD, ADHD with Tourette's, and depression. Adult studies support an antidepressant effect from repetitive TMS, but there is only one study that has been reported on 7 patients that used rTMS to the left dorsal prefrontal cortex on children/adolescents with depression (5 of the 7 subjects treated responded). Although there are limited studies using rTMS (in 34 children), these studies did not report significant adverse effects or seizures. Repetitive TMS safety, ethical, and neurotoxicity concerns also are discussed.

Adenocarcinoma fetal bien diferenciado de pulmón en una mujer de 26 años / Well differentiated fetal adenocarcinoma of the lung in a 26 year old woman

El adenocarcinoma fetal bien diferenciado de pulmón es un tumor raro compuesto por glándulas neoplásicas ricas en glucógeno y túbulos que se parecen al pulmón fetal entre la semana 10 y 16 de gestación[1]. Se presenta el caso de una mujer de 26 años, con antecedentes de bronquitis aguda y tabaquismo, cuyos hallazgos clínicos, imaginológicos, macroscópicos y microscópicos fueron indicativos de esta neoplasia. Se le practicó lobectomía inferior izquierda.

Well differentiated fetal adenocarcinoma is a rare lung tumour that is composed of glycogenrich neoplasic glands and tubules that resemble fetal lung at 10 to 16 weeks of gestation. In this report, we present a case of a 26 year old woman with a history of acute bronchitis and smoking, on which the clinical, imaging, macroscopic and microscopic features were compatible with this neoplasm. Lobectomy was performed of the left lower lobe.

Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial.

OBJECTIVES: Atomoxetine seems to be as effective for treating attention-deficit/hyperactivity disorder (ADHD) when the daily dose is administered once in the morning as when the dose is divided and administered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening and early morning. Another goal was to determine how early in treatment it was possible to discern a specific effect of the drug on ADHD symptoms. METHODS: This study was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 12 outpatient sites in the United States. A total of 197 children, 6 to 12 years of age, who had been diagnosed as having ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, were randomized to receive 8 weeks of treatment with atomoxetine or placebo, dosed once daily in the mornings. ADHD symptoms were assessed with parent and investigator rating scales. The primary outcome measure was the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score. Daily parent assessments of children's home behaviors in the evening and early morning were recorded with an electronic data entry system. This instrument measures 11 specific morning or evening activities, including getting up and out of bed, doing or completing homework, and sitting through dinner. RESULTS: Seventy-one percent of the children enrolled were male, 69% met criteria for the combined subtype (both inattentive and hyperactive/impulsive symptoms), and the most common psychiatric comorbidity was oppositional defiant disorder (35%). Once-daily atomoxetine (final mean daily dose of 1.3 mg/kg) was significantly more effective than placebo in treating core symptoms of ADHD. Mean reductions in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score were significantly greater for patients randomized to atomoxetine, beginning at the first visit after the initiation of treatment and continuing at all subsequent visits. Both inattentive and hyperactive/impulsive symptom clusters were significantly reduced with atomoxetine, compared with placebo. With continued treatment and dose titrations, core symptoms of ADHD continued to decrease throughout the 8-week study. Mean reductions in the daily parent assessment total scores for patients randomized to atomoxetine were superior during the first week, beginning with the first day of dosing, and were also superior at endpoint. Efficacy outcomes for the evening hours for atomoxetine-treated patients were superior to those for placebo-treated patients, as assessed with 2 different assessment scales. Decreases in the daily parent assessment morning subscores at endpoint showed a significant reduction in symptoms that lasted into the mornings. Rates of discontinuations attributable to adverse events were <5% for both groups. Adverse events reported significantly more frequently with atomoxetine were decreased appetite, somnolence, and fatigue. CONCLUSIONS: Among children 6 to 12 of age who had been diagnosed as having ADHD, once-daily administration of atomoxetine in the morning provided safe, rapid, continuous, symptom relief that lasted not only into the evening hours but also into the morning hours. Atomoxetine treatment was safe and well tolerated.

Paracoccidioidomicosis aislada de la glándula suprarrenal: reporte de caso / Isolated A drenal paracoccidioidomycosis: case report

A pesar de la relativa alta prevalencia de la paracoccidioidomicosis como forma sistémica en América Latina, la forma aislada, en especial la que afecta las glándulas suprarrenales, es infrecuente, con sólo dos casos reportados. En este artículo se presenta el caso de un hombre de 65 años de edad con manifestación clínica de insuficiencia adrenal, cuyo hallazgo por imágenes mostró una masa suprarrenal bilateral. La biopsia evidención, por otro lado, una afectación por Paracoccidioides brasiliensis.

Definiendo las caracteristicas operativas de la biopsia por congelacion en el departamento de patologia del Hospital Universitario de San Ignacio / Frozen section in Departament of pathology of Hospital Universitario de San Ignacio

La biopsia por congelación, o consulta intraoperatoria constituye una valiosa herramienta, para los médicos del área quirúrgica, los cuales ante un hallazgo dado deben tomar decisiones trascendentales, con grandes implicaciones médicas, estéticas o funcionales para sus pacientes. Por esto, es fundamental conocer las características operativas de este procedimiento en nuestro hospital. Para ello se revisaron todas las biopsias por congelación vistas en el departamento de patología del Hospital Universitario de San Ignacio entre el 1º de enero de 1993 y el 31 de diciembre de 1997, recolectando en total 643 procedimientos disponibles para el estudio. Se pudo establecer que en el Hospital Universitario de San Ignacio la prueba tiene una sensibilidad del 89.5 por ciento, una especificidad de 99.5 por ciento y una precisión global de 96.6 por ciento, con una tasa de resultados diferidos de 3.6 por ciento. Estas características operativas son notablemente similares a la referidas en la literatura médica mundial y nos permiten tanto a los patólogos como los cirujanos de las diversas áreas trabajar dentro de un marco de confianza y certeza