Evaluation of the effectiveness of the FOCUS ADHD App in monitoring adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The current investigation assessed a) the performance of the FOCUS ADHD mobile health application (App) in increasing pharmacological treatment adherence and improving patients' knowledge of attention-deficit/hyperactivity disorder (ADHD) and b) the impact of implementing a financial incentive for using the App (i.e., a discount on medication). METHODS: In a randomized, blind, parallel-group clinical trial, 73 adults diagnosed with ADHD were allocated into three groups for 3 months: a) Pharmacological treatment as usual (TAU); b) TAU and the App (App Group); and c) TAU and the App + a commercial discount on the purchase of medication prescribed for ADHD treatment (App + Discount Group). RESULTS: There was no significant difference in mean treatment adherence between groups, assessed as a medication possession ratio (MPR). However, the App + Discount Group exhibited greater medication intake registrations compared with the App Group during the initial phase of the trial. The financial discount also produced a 100% App adoption rate. App use did not increase ADHD knowledge, though knowledge scores were high at baseline. The usability and quality of the App were rated favorably. CONCLUSIONS: The FOCUS ADHD App achieved a high adoption rate and positive evaluations by users. Use of the App did not increase adherence to treatment as measured by MPR, but, for App users, the addition of a financial incentive to use the App produced an increase in treatment adherence in terms of medication intake registrations. The present results offer encouraging data for combining incentives with mobile digital health solutions to positively impact treatment adherence in ADHD.

Theophrastus's Anaisthetos Transdiagnostic Presentation: comment on Pehlivanidis and Papanikolaou (2022).

We were pleased to read Pehlivanidis and Papanikolaou's article1 and see that more colleagues are recognizing Theophrastus' text as the first description of Attention Deficit Hyperactivity Disorder (ADHD).2 We agree with the authors' perspective that Theophrastus' description may suggest the presence of more than one neurodevelopmental disorder. In fact, Theophrastus' description aligns with the shared clinical symptoms and underlying neurodevelopmental mechanisms of ADHD and Social Pragmatic Communication Disorder (SPCD). It is fascinating that a description from over 2000 years ago already presented prototypical individual transdiagnostic aspects that are compatible with a modern biological view of psychiatry. Indeed, it is not unexpected that heritable traits with clear biological underpinnings should have been perceived since the dawn of medicine. A significant leap forward in the development of this field came a few decades ago when Clements (1966)3 published a NIH-sponsored project entitled 'Minimal Brain Dysfunction in Children.' This seminal work prepared the terrain for the ongoing understanding of the grouping of signs, symptoms, and biological factors observed across various neurodevelopmental disorders. This grouping can be present in different spectrums, proportions, and nuances, including children and adults with some impairments that are not solely explained by their cognitive abilities. Thus, the characterization of 'The Obtuse Man' by Theophrastus could be considered a prototypical case of this more integrated and less fragmented view of what we call neurodevelopmental disorders.

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria.

As a biologic reservoir of Mycobacterium tuberculosis (M. tb), one-quarter of the world population is infected with the well-known latent tuberculosis (LTBI). About 5-10% of LTBI patients will progress to active disease in the first years after primary infection and, despite using the recommended treatment, 20% can still reactivate the infection. A new LTBI treatment could minimize adverse effects and antibiotic resistance that can occur when the same drug is used to treat the latent and active disease. New hydrazones were evaluated, and they showed great inhibitory activity against intramacrophagic and non-replicating M. tb, commonly found at this stage of infection, in addition to bactericidal and narrow-spectrum activity. When tested against eukaryotic cells, the hydrazones showed great safety at different exposure times. In vitro, these compounds performed better than isoniazid and could be considered new candidates for LTBI treatment, which may promote greater engagement in its prescription and adherence.

Feasibility trial of the dialectical behavior therapy skills training group as add-on treatment for adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: Our aim was to explore the feasibility, and efficacy of a Dialectical Behavior Therapy Skill Training Group (DBT-ST) as an add-on treatment for adult attention-deficit/hyperactivity disorder (ADHD) in Latin America. METHOD: Adults with ADHD (n = 31) with stable medication treatment for ADHD and residual symptoms (ASRS > 20) were randomly assigned to DBT-ST (n = 16) or treatment as usual (TaU; n = 15) for 12 weeks. Feasibility was accessed by attendance and completion rates at 12 weeks. Efficacy outcomes were measured with the ASRS, and performed at 0, 6, 12, and 16 weeks. RESULTS: The DBT-ST protocol had 81.25% completion rate, with a mean attendance of 87.25% of the sessions. No significant interactions between group and time were detected for outcome measures. DISCUSSION: The DBT-ST was feasible as add-on treatment for adult patients with ADHD in Latin America. Replicating previous findings, DBT-ST has shown no significantly higher improvement in ADHD symptoms in comparison with TaU. Registered at the Clinical Trials database (NCT03326427).

Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD.

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder.

Integrative proteomics and pharmacogenomics analysis of methylphenidate treatment response.

Transcriptomics and candidate gene/protein expression studies have indicated several biological processes modulated by methylphenidate (MPH), widely used in attention-deficit/hyperactivity disorder (ADHD) treatment. However, the lack of a differential proteomic profiling of MPH treatment limits the understanding of the most relevant mechanisms by which MPH exerts its pharmacological effects at the molecular level. Therefore, our aim is to investigate the MPH-induced proteomic alterations using an experimental design integrated with a pharmacogenomic analysis in a translational perspective. Proteomic analysis was performed using the cortices of Wistar-Kyoto rats, which were treated by gavage with MPH (2 mg/kg) or saline for two weeks (n = 6/group). After functional enrichment analysis of the differentially expressed proteins (DEP) in rats, the significant biological pathways were tested for association with MPH response in adults with ADHD (n = 189) using genome-wide data. Following MPH treatment in rats, 98 DEPs were found (P < 0.05 and FC < -1.0 or > 1.0). The functional enrichment analysis of the DEPs revealed 18 significant biological pathways (gene-sets) modulated by MPH, including some with recognized biological plausibility, such as those related to synaptic transmission. The pharmacogenomic analysis in the clinical sample evaluating these pathways revealed nominal associations for gene-sets related to neurotransmitter release and GABA transmission. Our results, which integrate proteomics and pharmacogenomics, revealed putative molecular effects of MPH on several biological processes, including oxidative stress, cellular respiration, and metabolism, and extended the results involving synaptic transmission pathways to a clinical sample. These findings shed light on the molecular signatures of MPH effects and possible biological sources of treatment response variability.

Attention-deficit hyperactivity disorder in ancient Greece: The Obtuse Man of Theophrastus.

We present an ancient Greek description written by the philosopher Theophrastus in his classic book ' Characters' comparable with modern attention-deficit hyperactivity disorder. The arguments are based in one chapter of this book-The Obtuse Man-presenting features of a character closely resembling the modern description of attention-deficit hyperactivity disorder. In a free comparative exercise, we compared Theophrastus descriptions with modern Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) attention-deficit hyperactivity disorder symptoms. The sentences describing The Obtuse Man written by Theophrastus are similar to several symptoms of attention-deficit hyperactivity disorder and he would probably be currently diagnosed with this disorder as an adult. To our knowledge, this is the oldest description compatible with the current conception of attention-deficit hyperactivity disorder in adults in the Western literature. Differently than the moralistic view of ancient Greece regarding those symptoms, the medical attention-deficit hyperactivity disorder conception may be advantageous to patients since it might reduce prejudice and allow individuals to seek treatment.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

OBJECTIVES: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. METHODS: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. RESULTS: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). CONCLUSION: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.

Should we keep on? Looking into pharmacogenomics of ADHD in adulthood from a different perspective.

A considerable proportion of adults with attention-deficit/hyperactivity disorder (ADHD) do not respond to the treatment with methylphenidate. This scenario could be due to inherited interindividual differences that may alter pharmacologic treatment response. In this sense, in 2012 we conducted a systematic search on PUBMED-indexed literature for articles containing information about pharmacogenomics of ADHD in adults. Five studies were found on methylphenidate pharmacogenomics and the only significant association was reported by one particular study. However, this single association with the SLC6A3 gene was not replicated in two subsequent reports. In the present review, although we could not find additional pharmacogenomics studies, we discuss these up-to-date findings and suggest new approaches for this field. Additionally, using systeomic-oriented databases, we provide a broad picture of new possible candidate genes as well as potential gene-gene interactions to be investigated in pharmacogenomics of persistent ADHD.

Severity but not comorbidities predicts response to methylphenidate in adults with attention-deficit/hyperactivity disorder: results from a naturalistic study.

Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.

Could comorbid bipolar disorder account for a significant share of executive function deficits in adults with attention-deficit hyperactivity disorder?

OBJECTIVE: The frequent comorbidity between attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BD) represents a challenge for disentangling specific impairments of each disorder in adulthood. Their functional impairments seem to be mediated by executive function deficits. However, little is known about the extent to which each executive function deficit might be disorder specific or explained by the comorbidity. The aim of the present study was to determine if comorbid BD could account for a significant share of executive function deficits when measured by the Wisconsin Card Sorting Test (WCST) in adults with ADHD. METHODS: Adult patients with ADHD and healthy subjects were evaluated in the ADHD outpatient Program at the Hospital de Clínicas de Porto Alegre. Psychiatric diagnoses were based on DSM-IV criteria. WCST scores were compared by multivariate analysis of covariance among three groups: ADHD with BD (n = 51), ADHD without BD (n = 278), and healthy subjects (n = 91). RESULTS: When compared to patients without BD and healthy subjects, patients with ADHD and comorbid BD showed lower scores in total correct answers (p = 0.003); higher scores in total errors (p = 0.004) and non-perseverative errors (p = 0.002); and completed fewer categories (p = 0.009). Patients with ADHD without BD did not differ from healthy subjects. CONCLUSIONS: WCST impairments among patients with ADHD seem to be to a large extent attributable to comorbid BD. Although other executive function deficits (e.g., in the inhibitory control domain) have been demonstrated to accompany ADHD, the present findings suggest that set-shifting deficits are strongly related to comorbid BD.

Genética além dos rótulos / Genetics beyond labels

A genética, ao longo de sua história, foi frequentemente vinculada a conceitos de imutabilidade e determinismo. Entretanto, o pertinente reconhecimento das interações complexas entre genes e ambiente apresenta-se como fundamental para o desenvolvimento de uma concepção não determinista do comportamento e dos transtornos mentais. Para contextualizar a visão sobre a genética psiquiátrica na área da saúde mental, discutimos, a partir de recortes históricos, o uso dessa ciência como justificativa para ações fora dos limites éticos. Além disso, trabalhamos a concepção da genética além dos rótulos, apresentando a questão da causa em transtornos mentais com uma abordagem centrada na interação gene x ambiente. Essa concepção está ligada à ideia de complexidade e heterogeneidade em oposição ao reducionismo determinista. Por fim, propomos uma abordagem integrada, apontando a necessidade de novos modelos que levem em consideração o caráter multifatorial dos transtornos mentais. Esses modelos podem não apenas auxiliar no entendimento das doenças, mas também no desenvolvimento de estratégias de prevenção e tratamento que minimizem o sofrimento advindo desses transtornos.(AU)

Genetics has been frequently linked to concepts of immutability and determinism throughout its history. However, the necessary acknowledgement of complex interactions between genes and environment is essential for the development of a non-determinist conception of behavior and mental disorders. In order to contextualize the scope of psychiatric genetics in the field of mental health, the way genetics was used as justification to unethical attitudes was discussed through a historical perspective. Besides that, we attempted to conceptualize genetics beyond labels, presenting the issue of cause in mental disorders through an approach centered in the gene vs. environment interaction. This conception is linked to the idea of complexity and heterogeneity as opposed to determinist reductionism. As a conclusion, we suggest an integrated approach pointing to the need of new models that consider the multifactorial character of mental disorders. Furthermore, these models can not only help in the understanding of diseases, but also in the development of prevention and treatments strategies that could minimize the suffering brought by these disorders.(AU)

Pharmacogenetics of response to methylphenidate in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review.

Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a considerable proportion of adult patients who do not respond to treatment with MPH or discontinue drug therapy. Since effects of genetic variants in the response to MPH treatment might explain these negative outcomes, we conducted an electronic systematic search of MEDLINE-indexed literature looking for articles containing information about pharmacogenetics of ADHD in adults published until January, 2012. The keywords used were 'ADHD', 'Attention-Deficit/Hyperactivity Disorder' and 'gene' in combination with methylphenidate, amphetamine or atomoxetine. Only 5 pharmacogenetic studies on adult ADHD met inclusion criteria. The results evidenced that most findings obtained so far are negative, and all studies focused on MPH response. There is only one positive result, for a polymorphism at the dopamine transporter gene (DAT1) gene. The current state of the art in adult ADHD implies that pharmacogenetic tests are far from routine clinical practice. However, the integration of these studies with neuroimaging and neuropsychological tests may help to understand mechanisms of drug action and the pathophysiology of ADHD.

Cognitive deficits in adults with ADHD go beyond comorbidity effects.

OBJECTIVE: This study addresses if deficits in cognitive, attention, and inhibitory control performance in adults with ADHD are better explained by the disorder itself or by comorbid conditions. METHOD: Adult patients with ADHD (n = 352) and controls (n = 94) were evaluated in the ADHD program of a tertiary hospital. The diagnostic process for ADHD and comorbidities was based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria. Stepwise regression analyses evaluated the effect of ADHD, demographics, and comorbidities on the scores from Wechsler Adult Intelligence Scale-Revised, Continuous Performance Test, and Stroop Color and Word Test. RESULTS: Patients with ADHD of both genders had worse performance on neuropsychological domains, even after adjustment for comorbidities. The presence of comorbid bipolar disorder and specific phobia are associated with more Stroop errors, whereas patients with generalized anxiety disorder present a longer execution time in Stroop. CONCLUSION: Neuropsychological deficits in adults with ADHD go beyond comorbidity. Specific comorbid disorders may influence the neuropsychological functioning in adults with ADHD.

No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD.

Results from pharmacogenetic investigations of methylphenidate (MPH) response in patients with ADHD are still inconsistent, especially among adults. This study investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT, and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen owing to previous evidence for an influence in ADHD susceptibility. No significant differences in allele or genotype frequencies between MPH responders and nonresponders were detected. In conclusion, our findings do not support an effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

Síndrome cardiorrenal como predictor de mala evolución intrahospitalaria en pacientes añosos internados con insuficiencia cardíaca / Cardio-renal syndrome at admission as a predictor of worse in hospital outcome in elderly patients hospitalized with heart failure / Síndrome cardio-renal como um preditor de pior evoluþÒo intra-hospitalar em pacientes idosos hospitalizados com insuficiÛncia cardíaca

Introducción. Existe una alta prevalencia de disfunción renal en la población de pacientes con insuficiencia cardíaca (IC). El término síndrome cardiorrenal (SCR) define el proceso por el que la disfunción de uno de los órganos induce la disfunción del otro. El objetivo es evaluar si la presencia de SCR al ingreso hospitalario es un factor pronóstico de mala evolución intrahospitalaria (MEIH) en pacientes añosos internados por IC. Material y métodos. Se incluyeron en forma retrospectiva los pacientes de una población añosa internados desde Junio de 2009 a Marzo de 2011 en la Unidad Coronaria con diagnóstico de IC. Se separaron en 2 grupos: con SCR, definido como creatininemia mayor de 1,5 mg/dL y uremia mayor de 55 mg/dL, y sin SCR. Se consideró disfunción sistólica del ventrículo izquierdo (DSVI) a la fracción de eyección menor del 45%. Se analizaron los antecedentes, datos de ingreso y evolución intrahospitalaria. El punto final MEIH se definió como muerte intrahospitalaria, requerimiento de inotrópicos por más de 48 horas o la necesidad de asistencia respiratoria mecánica. La necesidad de diálisis o ultrafiltración no se incluyó en la MEIH para descartar una posible relación directa entre dicha complicación y el SCR. Los resultados se enuncian como media ± desvío estándar, las comparaciones se realizaron de acuerdo al tipo de variable y el análisis multivariado se llevó a cabo mediante regresión logística. Resultados. Se analizaron en total 196 pacientes (107 mujeres) con una edad de 78 ± 8,3 años, 45 con SCR (23%). Los pacientes con SCR presentaron una uremia de 125 ± 56 mg/dL y una creatininemia de 2,91 ± 2,0 mg/dL. A su vez, los 151 pacientes sin SCR tuvieron una uremia de 53 ± 23 mg/dL y una creatinina de 0,98 ± 0,29 mg/ dL. En el grupo con SCR, el 60% (27 pacientes) fueron hombres vs el 41% (62 pacientes) en el grupo sin SCR (p<0,03). No hubo diferencias significativas entre los grupos con y sin SCR en los antecedentes de diabetes (31% vs 22%), hipertensión arterial (92% vs 86%), fibrilación auricular (38% vs 36%), infarto de miocardio previo (13% vs 11%), tabaquismo (10,5% vs 8,3%) y dislipidemia (40% vs 34%). Entre los pacientes con SCR, hubieron más antecedentes de anemia (47% vs 16%; p=0,0001) y menor hematocrito al ingreso (34% vs 38%; p<0,003). En tanto, no fueron significativas las diferencias entre los grupos con y sin SCR en los antecedentes de enfermedad pulmonar obstructiva crónica (EPOC) (16% vs 10%), en la frecuencia cardíaca al ingreso (90 ± 25 lpm vs 96± 26 lpm), en la presión arterial sistólica (151 ± 32 mm Hg vs 152 ± 34 mm Hg) y en la natremia (135 ± 7 mEq/L vs 136 mEq/L). Un total de 34 pacientes (17%) presentó MEIH, 15 en el grupo con SCR (33%) y 19 en el grupo sin SCR (13%), p=0,003. En el análisis multivariado, resultaron predictores independientes de MEIH la presencia de SCR (OR 2,89 1,23-6,79, p<0,02), la de EPOC (OR 4,88 1,63-14,56, p<0,005), la natremia (OR 0,93 0,87-0,99, p<0,03) y la frecuencia cardíaca (OR 0,98 0,96-0,99, p<0,04). La uremia y la creatininemia, que definen el SCR, fueron por su parte predictores independientes que tienden a cancelarse entre sí. Conclusión. En pacientes añosos internados por IC, el SCR, definido por la elevación simultánea de la uremia y la creatininemia, fue más frecuente en los hombres y se comportó como predictor independiente de MEIH, junto con el antecedente de EPOC, la hiponatremia y una menor frecuencia cardíaca. En tanto, el hematocrito, que se halló disminuido en el SCR, no se relacionó con la presencia de MEIH, como tampoco lo hicieron la edad avanzada ni la DSVI, tal como fuera definida en el estudio.(AU)

Background. There is a high prevalence of renal dysfunction in the population of patients with heart failure (HF). The term cardio-renal syndrome (CRS) defines the process by which a dysfunction of organs induces dysfunction of the other. The aim is to evaluate whether the presence of CRS at hospital admission is a predictor of worse in hospital outcome in elderly patients hospitalized with HF. Methods and material. Elderly patients admitted to the Coronary Care Unit with a diagnosis of heart failure between June 2009 and March 2011 were selected to be included in this analysis. They were divided into two groups: with definitive CRS, defined as blood creatinine more than 1.5 mg/dL and blood urea more than 55 mg/dL and without CRS. An ejection fraction less than 45% by echocardiography (Simpson) was considered as significant systolic dysfunction. The previous patients clinical history, condition on admittance and in hospital progress were analyzed. Worse hospital outcome (WHO) end points were defined as death, need for inotropic for more than 48 hours or the need for mechanical ventilation. The need for dialysis or ultra filtration was not considered to avoid a possible bias with that complication and CRS. The results are presented as the median ± standard deviation, the comparisons were performed according to the type of variable and the multivariate analysis was performed by logistic regression. Results. A total of 196 patients (107 women) with an average age of 78 ± 8.3 years were analyzed, 45 had CRS. Patients with CRS had a blood urea of 125 ± 56 mg/dl and a creatinine level of 2.91 ± 2.0 mg/dl. The 151 patients without CRS had a blood urea of 53 ± 23 mg/dl and a creatinine level of 0.98 ± 0.29 mg/dl. In the CRS 60% (27 patients) were men vs 41% (62 patients) in the group without CRS (p=0.03). There was no significant difference between both groups as far as diabetes (31% vs 22%), hypertension (92% vs 86%), atrial fibrillation (38% vs 36%), previous myocardial infarction (13% vs 11%), and smoking (10.5% vs 8.3%). In patients with CRS there were more with previous history of anemia and lower hematocrit at admittance (34% vs 38%, p=0.003). Whereas, there was no significant difference between the both groups in the presence of chronic obstructive pulmonary disease (COPD) (16% vs 10%), heart rate at entry (90 ± 25 bpm vs 96 ± 26 bpm), arterial systolic pressure (151 ± 32 mm Hg vs 152 ± 34 mm Hg) and blood sodium (135 ± 7 mEq/L vs 136 mEq/L). A total of 34 patients (17%) meets the criteria of WHO, 15 in the group with CRS (33%) and 19 (13%) in the non CRS, p=0.003. In the multivariate analysis

Síndrome cardiorrenal como predictor de mala evolución intrahospitalaria en pacientes añosos internados con insuficiencia cardíaca / Cardio-renal syndrome at admission as a predictor of worse in hospital outcome in elderly patients hospitalized with heart failure / Síndrome cardio-renal como um preditor de pior evolução intra-hospitalar em pacientes idosos hospitalizados com insuficiência cardíaca

Introducción. Existe una alta prevalencia de disfunción renal en la población de pacientes con insuficiencia cardíaca (IC). El término síndrome cardiorrenal (SCR) define el proceso por el que la disfunción de uno de los órganos induce la disfunción del otro. El objetivo es evaluar si la presencia de SCR al ingreso hospitalario es un factor pronóstico de mala evolución intrahospitalaria (MEIH) en pacientes añosos internados por IC. Material y métodos. Se incluyeron en forma retrospectiva los pacientes de una población añosa internados desde Junio de 2009 a Marzo de 2011 en la Unidad Coronaria con diagnóstico de IC. Se separaron en 2 grupos: con SCR, definido como creatininemia mayor de 1,5 mg/dL y uremia mayor de 55 mg/dL, y sin SCR. Se consideró disfunción sistólica del ventrículo izquierdo (DSVI) a la fracción de eyección menor del 45%. Se analizaron los antecedentes, datos de ingreso y evolución intrahospitalaria. El punto final MEIH se definió como muerte intrahospitalaria, requerimiento de inotrópicos por más de 48 horas o la necesidad de asistencia respiratoria mecánica. La necesidad de diálisis o ultrafiltración no se incluyó en la MEIH para descartar una posible relación directa entre dicha complicación y el SCR. Los resultados se enuncian como media ± desvío estándar, las comparaciones se realizaron de acuerdo al tipo de variable y el análisis multivariado se llevó a cabo mediante regresión logística. Resultados. Se analizaron en total 196 pacientes (107 mujeres) con una edad de 78 ± 8,3 años, 45 con SCR (23%). Los pacientes con SCR presentaron una uremia de 125 ± 56 mg/dL y una creatininemia de 2,91 ± 2,0 mg/dL. A su vez, los 151 pacientes sin SCR tuvieron una uremia de 53 ± 23 mg/dL y una creatinina de 0,98 ± 0,29 mg/ dL. En el grupo con SCR, el 60% (27 pacientes) fueron hombres vs el 41% (62 pacientes) en el grupo sin SCR (p<0,03). No hubo diferencias significativas entre los grupos con y sin SCR en los antecedentes de diabetes (31% vs 22%), hipertensión arterial (92% vs 86%), fibrilación auricular (38% vs 36%), infarto de miocardio previo (13% vs 11%), tabaquismo (10,5% vs 8,3%) y dislipidemia (40% vs 34%). Entre los pacientes con SCR, hubieron más antecedentes de anemia (47% vs 16%; p=0,0001) y menor hematocrito al ingreso (34% vs 38%; p<0,003). En tanto, no fueron significativas las diferencias entre los grupos con y sin SCR en los antecedentes de enfermedad pulmonar obstructiva crónica (EPOC) (16% vs 10%), en la frecuencia cardíaca al ingreso (90 ± 25 lpm vs 96± 26 lpm), en la presión arterial sistólica (151 ± 32 mm Hg vs 152 ± 34 mm Hg) y en la natremia (135 ± 7 mEq/L vs 136 mEq/L). Un total de 34 pacientes (17%) presentó MEIH, 15 en el grupo con SCR (33%) y 19 en el grupo sin SCR (13%), p=0,003. En el análisis multivariado, resultaron predictores independientes de MEIH la presencia de SCR (OR 2,89 1,23-6,79, p<0,02), la de EPOC (OR 4,88 1,63-14,56, p<0,005), la natremia (OR 0,93 0,87-0,99, p<0,03) y la frecuencia cardíaca (OR 0,98 0,96-0,99, p<0,04). La uremia y la creatininemia, que definen el SCR, fueron por su parte predictores independientes que tienden a cancelarse entre sí. Conclusión. En pacientes añosos internados por IC, el SCR, definido por la elevación simultánea de la uremia y la creatininemia, fue más frecuente en los hombres y se comportó como predictor independiente de MEIH, junto con el antecedente de EPOC, la hiponatremia y una menor frecuencia cardíaca. En tanto, el hematocrito, que se halló disminuido en el SCR, no se relacionó con la presencia de MEIH, como tampoco lo hicieron la edad avanzada ni la DSVI, tal como fuera definida en el estudio.

Background. There is a high prevalence of renal dysfunction in the population of patients with heart failure (HF). The term cardio-renal syndrome (CRS) defines the process by which a dysfunction of organs induces dysfunction of the other. The aim is to evaluate whether the presence of CRS at hospital admission is a predictor of worse in hospital outcome in elderly patients hospitalized with HF. Methods and material. Elderly patients admitted to the Coronary Care Unit with a diagnosis of heart failure between June 2009 and March 2011 were selected to be included in this analysis. They were divided into two groups: with definitive CRS, defined as blood creatinine more than 1.5 mg/dL and blood urea more than 55 mg/dL and without CRS. An ejection fraction less than 45% by echocardiography (Simpson) was considered as significant systolic dysfunction. The previous patient's clinical history, condition on admittance and in hospital progress were analyzed. Worse hospital outcome (WHO) end points were defined as death, need for inotropic for more than 48 hours or the need for mechanical ventilation. The need for dialysis or ultra filtration was not considered to avoid a possible bias with that complication and CRS. The results are presented as the median ± standard deviation, the comparisons' were performed according to the type of variable and the multivariate analysis was performed by logistic regression. Results. A total of 196 patients (107 women) with an average age of 78 ± 8.3 years were analyzed, 45 had CRS. Patients with CRS had a blood urea of 125 ± 56 mg/dl and a creatinine level of 2.91 ± 2.0 mg/dl. The 151 patients without CRS had a blood urea of 53 ± 23 mg/dl and a creatinine level of 0.98 ± 0.29 mg/dl. In the CRS 60% (27 patients) were men vs 41% (62 patients) in the group without CRS (p=0.03). There was no significant difference between both groups as far as diabetes (31% vs 22%), hypertension (92% vs 86%), atrial fibrillation (38% vs 36%), previous myocardial infarction (13% vs 11%), and smoking (10.5% vs 8.3%). In patients with CRS there were more with previous history of anemia and lower hematocrit at admittance (34% vs 38%, p=0.003). Whereas, there was no significant difference between the both groups in the presence of chronic obstructive pulmonary disease (COPD) (16% vs 10%), heart rate at entry (90 ± 25 bpm vs 96 ± 26 bpm), arterial systolic pressure (151 ± 32 mm Hg vs 152 ± 34 mm Hg) and blood sodium (135 ± 7 mEq/L vs 136 mEq/L). A total of 34 patients (17%) meets the criteria of WHO, 15 in the group with CRS (33%) and 19 (13%) in the non CRS, p=0.003. In the multivariate analysis independent predictors of WHO were the presence of CRS (OR 2.891.23-6.79, p=0.02), COPD (OR 4.88 1.63-14.56, p=0.005), blood sodium (OR 0.93 0.87-0.99, p=0.03) and heart rate (OR 0.98 0.96-0.99, p=0.04). Although blood urea and creatinine define CRS and were independent predictors, they tended to cancel themselves out. Conclusion. In elderly patients hospitalized because of heart failure CRS, defined by simultaneous increase of blood urea and creatinine, was more frequent in males and was an independent predictor of worse outcome, as was also COPD, hyponatremia and lower heart rate. Whereas hematocrit, which was found to be low in CRS, was not related to worse development, neither was advanced age or systolic dysfunction as defined in this study.

Introdução. Existe uma alta prevalência de disfunção renal na população de pacientes com insuficiência cardíaca (IC). O termo síndrome cardio-renal (SCR) define o processo pelo qual uma disfunção de órgãos induz disfunção do outro. O objetivo é avaliar se a presença de SCR na admissão é um preditor de pior evolução intra-hospitalar (PEIH) em pacientes idosos hospitalizados por insuficiência cardíaca. Material e métodos. Retrospectivamente foram incluídos pacientes idosos hospitalizados entre Junho de 2009 a Março de 2011 na Unidade de Terapia Coronariana com diagnóstico de insuficiência cardíaca. Foram separados em dois grupos: com SCR, definida como creatinina sérica > 1,5 mg/dL e uremia > 55 mg/dL, e sem SCR. Considerou-se disfunção sistólica ventricular esquerda (DSVE) para a fração de ejeção é inferior a 45%. Foram analisados os registros, entrada de dados e resultados hospital. O ponto final PEIH foi definido como morte intra-hospitalar, o uso de inotrópicos por mais de 48 horas ou a necessidade de ventilação mecânica. A necessidade de diálise ou ultrafiltração não foi incluída no PEIH para excluir uma relação direta entre esta complicação e SCR. Os resultados são expressos como média ± desvio padrão, as comparações foram feitas de acordo com o tipo de análise multivariada variável e foi realizada utilizando regressão logística. Resultados. Foram analisados de 196 pacientes (107 mulheres) com idades entre 78 ± 8,3 anos, 45 com SCR (23%). O PT apresentou com SCR uréia e creatinina 125 ± 56 2,91 ± 2,0. Por sua vez, os 151 pacientes com SCR sem uréia foi de 53 ± 23 e creatinina de 0,98 ± 0,29. No grupo com SCR 60% (27 pacientes) eram do sexo masculino, contra 41% (62 pacientes) no grupo sem SCR (p<0,03). Não houve diferenças significativas entre os grupos com e sem SCR na história do diabetes (31% vs 22%), hipertensão arterial (92% vs 86%), fibrilação atrial (38% vs 36%) infarto do miocárdio prévio (13% vs 11% ), tabagismo (10,5% vs 8,3%) e dislipidemia (40% vs 34%). Entre os pacientes com SCR tinha mais história de anemia (47% vs 16%, p=0,0001) e hematócrito abaixo de admissão (34% vs 38%, p<0,003). Entretanto, houve diferenças significativas entre os grupos com e sem SCR na história da doença pulmonar obstrutiva crônica (DPOC) (16% vs 10%), freqüência cardíaca no momento da admissão (90 ± 25 vs 96 ± 26), pressão arterial sistólica (151 ± 32 vs 152 ± 34) e sódio sérico (135 ± 7 vs 136). Um total de 34 pacientes (17%) teve MEIH, 15 no grupo com SCR (33%) e 19 no grupo sem SCR (13%), p=0,003. Na análise multivariada, os preditores independentes da PEIH foram a presença de SCR (OR 2,89 1,23-6,79, p<0,02), DPOC (OR 4,88 1,63-14,56, p<0,005), o sódio sérico (OR 0,93 0,87-0,99, p<0,03) e a freqüência cardíaca (OR 0,98 0,96-0,99, p<0,04). Á uréia e creatinina, que definem o SCR, foram preditores independentes, por sua vez tendem a anular-se mutuamente. Conclusão. Em pacientes idosos hospitalizados por insuficiência cardíaca, o SCR definido pela elevação simultânea de uréia e creatinina foi mais comum em homens e como um preditor independente de PEIH, juntamente com uma história de DPOC, hiponatremia e redução da freqüência cardíaca. Enquanto isso, o hematócrito foi encontrado diminuição no SCR, não relacionada com a presença de PEIH, e nem os idosos ou DSVE foi definida como no estudo.

Does age of onset of impairment impact on neuropsychological and personality features of adult ADHD?

The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n = 415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two ages of onset groups (before 7; n = 209 or from 7 to 12 years; n = 206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively P = 0.016 and P = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.

The role of a lifetime history of oppositional defiant and conduct disorders in adults with ADHD: implications for clinical practice.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is still under discussion. This study analyzes how the current clinical presentation of adult ADHD might be influenced by a lifetime history of CD and ODD. METHODS: We compared three groups of patients: ADHD without history of CD/ODD (n = 178), ADHD + history of ODD (n = 184), and ADHD + history of CD (n = 96). RESULTS: A history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. CONCLUSION: Past CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the importance of actively assessing the developmental history of adult ADHD patients.

Smoking and ADHD: an evaluation of self medication and behavioral disinhibition models based on comorbidity and personality patterns.

OBJECTIVE: The prevalence of smoking is significantly increased among adults with Attention-Deficit/Hyperactivity Disorder (ADHD), and this association has a significant impact in both disorders, ascribed to either self-medication or behavioral disinhibition hypotheses. However, little is known about clinical variables associated with cigarette smoking among patients with ADHD. The present study evaluates comorbidity, demographic and personality profiles of patients with ADHD in relation to smoking status. METHODS: Patients (n422) were evaluated in the adult ADHD outpatient clinic of Hospital de Clínicas de Porto Alegre. Diagnoses were based on DSM-IV criteria and interviews were performed with Portuguese version of K-SADS-E for ADHD and Oppositional-Defiant Disorder. Axis I psychiatric comorbidities were evaluated with the SCID-I and smoking behavior with Fagerström Test for Nicotine Dependence (FTND). Personality was evaluated with Cloninger's Temperament and Character Inventory (TCI). RESULTS: The presence of smoking was strongly associated with externalizing characteristics as antisocial personality disorder (OR4.2) and substance dependence (OR6.5), but not with internalizing disorders. Moreover, smoking was associated with higher novelty seeking and lower harm avoidance scores. CONCLUSIONS: Smoking initiation among patients with ADHD is consistent with a behavioral disinhibition profile beyond the possible role of self-medication in smoking persistence. Smoking in these patients is strongly associated with externalizing comorbid disorders.