Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine

Rationale

Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD). Although animal models have provided evidence that brain-derived neurotrophic factor (BDNF) is involved in the effects of ATX in the brain, there are no studies of BDNF in ADHD patients undergoing treatment with ATX.

Objectives

The aim of this study was to evaluate the possible changes in serum levels of BDNF in adults treated with ATX and its relationship with clinical improvement.

Methods

A total of 54 adults with ADHD (age 33.43?±?8.99 years) without any medical or psychiatric comorbidities were treated with ATX for 3 months; 35 of them completed the protocol. The clinical data for ADHD diagnosis, including Conners’ ADHD Rating Scale and blood samples, were collected at baseline (V1) and at the end of the treatment (V2).

Results

Adults with ADHD who completed ATX treatment for 3 months showed a significant improvement in their clinical symptoms. No significant differences were found in BDNF levels before and after treatment with ATX in the whole group of patients (p?=?0.15). The inattentive subgroup of ATX responders showed a decrease of serum BDNF after 3 months of ATX treatment (p?=?0.05) not present in the combined subtype (p?=?0.82).

Conclusions

These results suggest that BDNF is not directly involved in the neurobiological mechanisms of ATX-induced improvement of clinical symptoms of ADHD. The differences between the combined and inattentive subtypes in serum BDNF changes suggest selective ATX-induced effects in the function of brain circuitry.     

Theoretical and Experimental Identification of Frequency Characteristics and Control Signals of a Dynamic System in the Process of Turning

The article presents the results of the experimental validation of the developed static, time and frequency characteristics under interference and longitudinal feed control of a dynamic system in the process of turning axisymmetric parts. The experiments were conducted on a test bench, consisting of a 16B16P center lathe, a measuring system and a PC with a measurement card. The experiments were carried out to verify the assumptions of the baseline model of the turning process. As part of the study, we determined the static characteristics of the machining process, the time characteristics of the object under interference and under longitudinal feed rate control, and the frequency characteristics of the machine tool system under longitudinal feed rate control. During the experiments, we recorded the observed input and output signal curves and the observed characteristics of the interferences acting on the object, as well as the numerical values of the parameters of the equations describing the model, and in particular the gain of the elastic system, which is difficult to determine by analytical methods. The positive results of the experiments confirm the effectiveness of the proposed models and their usefulness for automation of machining processes.     

Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus infection in transplanted patients

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.     

Sarcoidosis in patients with chronic hepatitis C virus infection: analysis of 68 cases

We describe the clinical characteristics, the patterns of association, and the role of antiviral therapies in patients with sarcoidosis associated with chronic hepatitis C virus (HCV) infection. Sixty-eight patients were included in the current study, 56 cases identified in the literature search plus 12 unpublished cases from our department. In 50 HCV patients, sarcoidosis appeared after starting antiviral therapy. Antiviral therapy associated with triggered sarcoidosis consisted of alpha-interferon monotherapy in 20 cases and combined therapy with alpha-interferon and ribavirin in 30. Sarcoidosis appeared during the first 6 months after starting therapy in 66% of patients. The clinical picture of sarcoidosis included predominantly pulmonary disease in 38 (76%) patients and cutaneous sarcoidosis in 30 (60%). Antiviral therapy was discontinued in 60% of patients and continued or adjusted in 14%, while sarcoidosis appeared after completed therapy in the remaining cases. Specific therapy for sarcoidosis was started in only 21 patients, mainly with oral corticosteroids. The outcome of patients was detailed in 46 cases: remission or improvement was observed in 38/46 (83%) patients, stabilization of sarcoidosis in 5/46 (11%), and reactivation of sarcoidosis after an initial improvement in 3/46 (6%). Finally, 18 treatment-naive HCV patients presented sarcoidosis, with 14/18 (87%) patients presenting with pulmonary involvement and 8/18 (44%) with cutaneous involvement.In summary, sarcoidosis may be observed in HCV patients in 2 different situations: triggered by antiviral therapy (in 75% of cases) and unrelated to treatment. Sarcoidosis during antiviral therapy may present mainly as cutaneous or pulmonary disease, with a benign, uncomplicated evolution in more than 85% of cases. However, more complicated cases are observed, especially in HCV patients with preexisting sarcoidosis and/or with previous antiviral treatment. Clinicians should be aware of the possibility that sarcoidosis may initially manifest or be reactivated during or shortly after treatment with antiviral therapy in patients with chronic HCV infection.     

Prevalencia de las potenciales interacciones medicamentosas entre los antivirales de acción directa pangenotípicos y la medicación concomitante asociada a los pacientes con infección del virus de la hepatitis C crónica en España

ObjectiveTo determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain.MethodsRetrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (< 50 and ≥ 50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P < .05.Results3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18–49 years (28.9%) and ≥ 50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥ 50 years (8.6%, 43.8% and 12.4%, respectively, P < .001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P < .001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P < .001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P < .001) compared to GLE/PIB and SOF/VEL/VOX, respectively.ConclusionsPatients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions.     

Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial

OBJECTIVES: To evaluate further in a phase III, double blind trial the efficacy of infliximab in patients with active psoriatic arthritis (PsA), as observed in the smaller IMPACT trial. METHODS: 200 patients with active PsA unresponsive to previous treatment were randomised to infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22. Patients with inadequate response entered early escape at week 16. The primary measure of clinical response was ACR20. Other measures included Psoriatic Arthritis Response Criteria (PsARC), Psoriasis Area and Severity Index (PASI), and dactylitis and enthesopathy assessments. RESULTS: At week 14, 58% of patients receiving infliximab and 11% of those receiving placebo achieved an ACR20 response and 77% of infliximab patients and 27% of placebo patients achieved PsARC (both p<0.001). Among the 85% of patients with at least 3% body surface area psoriasis involvement at baseline, 53/83 (64%) patients receiving infliximab had at least 75% improvement in PASI compared with 2/87 (2%) patients receiving placebo at week 14 (p<0.001). These therapeutic effects were maintained through the last evaluation (week 24). Fewer infliximab patients than placebo patients had dactylitis at week 14 (18% v 30%; p = 0.025) and week 24 (12% v 34%; p<0.001). Fewer infliximab patients (22%) than placebo patients (34%) had active enthesopathy at week 14 (p = 0.016); corresponding figures at week 24 were 20% and 37% (p = 0.002). Infliximab was generally well tolerated, with a similar incidence of adverse events in each group. CONCLUSIONS: Infliximab 5 mg/kg through 24 weeks significantly improved active PsA, including dactylitis and enthesopathy, and associated psoriasis.