Prospective evaluation of hydroxychloroquine in pediatric interstitial lung diseases

Background: Interstitial lung diseases in children (chILD) are rare and consist of many different entities that affect the parenchyma of the lungs, leading to a chronic lung disease. The natural course of many of these diseases is connected with a high morbidity and significant mortality. Symptomatic treatment consists of oxygen supplementation, adequate nutrition adapted to the high energy demand generated by the disease due to the increased breathing effort required, as well as immunization against respiratory pathogens to prevent exacerbations through respiratory infections. No proven pharmacological treatments are available to date. This placebo-controlled study aims to evaluate the efficacy and safety of the mid-term use of hydroxychloroquine in chILD. Methods and design: The study is an explorative, prospective, randomized, double-blind, placebo-controlled investigation of hydroxychloroquine (HCQ) in chILD. Patients can be included into the trial when diagnosed with a chronic (≥ 3 weeks' duration) diffuse parenchymal lung disease (chILD) (1) genetically defined, (2) histologically defined or (3) diagnosed with idiopathic pulmonary hemorrhage (hemosiderosis). The study contains of two different study blocks, a START and a STOP block, which can be initiated in any sequence. Each patient can participate in each block only once. In the START block subjects are randomized to parallel groups for 4 weeks treatment, then the placebo group is switched to the active drug. In the STOP block, subjects taking HCQ are randomized into parallel groups treated with placebo or HCQ. Discussion: This study is the first international, investigator-initiated, prospective and controlled investigation of a pharmacological treatment in chILD. The block design was selected as it has the advantage of accommodating patients who are initiating or withdrawing from HCQ therapy, thus allowing the participation of those who were previously started on off-label HCQ. The cross-over design and selected outcome parameters enables us to include appropriate numbers of patients of all age groups from neonates to adults suffering from these rare diseases. Trial registration: This is an exploratory, Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multinational study investigating the initiation or withdrawal of hydroxychloroquine in subjects with chILD. Study title: Hydroxychloroquine in pediatric ILD: START randomized controlled in parallel groups, then switch placebo to the active drug, and STOP randomized controlled in parallel groups to evaluate the efficacy and safety of hydroxychloroquine (HCQ). Short title: HCQ in pediatric ILD, particularly 4surfdefect. EudraCT, ID: 2013-003714-40. Registered on 2 July 2013. ClinicalTrials.gov, ID: NCT02615938. Registered on 8 November 2015. IZKS trial code: 2013-006; Sponsor: University Hospital, Ludwig-Maximilians University of Munich. Responsible Party: Prof. Dr. med. Matthias Griese, University Hospital, Ludwig-Maximilians University of Munich, Germany

Nabelvenenkatheter- und periphere zentrale katheterassoziierte Komplikationen bei Frühgeborenen mit einem Geburtsgewicht < 1250 g : Ergebnisse einer Umfrage in Österreich und Deutschland

Background and objective Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight < 1250 g and associated rates of catheter-related adverse events. Methods Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). Results In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1–10 days were bacterial infection: 4.2 ± 3.4% (range 0–10%); thrombosis: 7.3 ± 7.1% (0–20%); emboli: 0.9 ± 2.0% (0–5%); organ injury: 1.1 ± 1.9% (0–5%); cardiac arrhythmia: 2.2 ± 2.5% (0–5%); and dislocation: 5.4 ± 8.7% (0–30%); and for PICCs with a dwell time of 1–14 days bacterial infection: 15.0 ± 3.4% (range 2.5–30%); thrombosis; 4.3 ± 3.5% (0–10%); emboli: 0.8 ± 1.6% (0–5%); organ injury: 1.5 ± 2.3% (0–5%); cardiac arrhythmia: 1.5 ± 2.3% (0–5%), and dislocation: 8.5 ± 4.6% (0–30%). Conclusion The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.Hintergrund und Ziel Nabelvenenkatheter („umbilical venous catheters“ [UVC]) und periphere zentrale Venenkatheter (PICC) werden häufig bei Frühgeborenen eingesetzt, sind jedoch mit einer Reihe von schwerwiegenden Komplikationen verbunden. In Österreich und Deutschland wurde eine Umfrage durchgeführt, um die Verwendung von UVC und PICC bei Frühgeborenen mit einem Geburtsgewicht < 1250 g und die damit verbundenen Raten von katheterbedingten unerwünschten Ereignissen zu bewerten. Methoden Elektronische Befragung der teilnehmenden Zentren der NeoVitaA-Studie. Hauptergebnisparameter waren die gemeldeten Raten von UVC- und PICC-assoziierten Komplikationen (Infektion, Thrombose, Embolie, Organverletzung, Arrhythmie, Dislokation, Sonstiges). Ergebnisse Insgesamt wurden 20 neonatale Intensivstationen (NICU) mit maximaler Intensivpflege in Österreich und Deutschland (Level I) kontaktiert, wobei 12/20 (60 %) von leitenden Neonatologen beantwortet wurden. Die gemeldeten Raten für UVC mit einer Verweildauer von 1 bis 10 Tagen waren bakterielle Infektionen: 4,2 ± 3,4 % (Bereich: 0–10 %); Thrombose: 7,3 ± 7,1 % (0–20 %); Embolie: 0,9 ± 2,0 % (0–5 %); Organverletzung: 1,1 ± 1,9 % (0–5 %); Herzrhythmusstörungen: 2,2 ± 2,5 % (0–5 %); und Dislokation: 5,4 ± 8,7% (0–30 %); und bei PICC mit einer Verweildauer von 1 bis 14 Tagen bakterielle Infektionen: 15,0 ± 3,4 % (Bereich: 2,5–30 %); Thrombose: 4,3 ± 3,5 % (0–10 %); Embolie: 0,8 ± 1,6 % (0–5 %); Organverletzung: 1,5 ± 2,3 % (0–5 %); Herzrhythmusstörungen: 1,5 ± 2,3 % (0–5 %) und Verrenkungen: 8,5 ± 4,6 % (0–30 %). Schlussfolgerung Die in dieser Umfrage berichteten katheterbedingten Komplikationsraten unterschieden sich zwischen UVC und PICC und waren höher als die in der Literatur berichteten. Um zuverlässigere Daten zu diesem klinisch wichtigen Thema zu erhalten, ist eine große prospektive, multizentrische, randomisierte, kontrollierte Studie geplant, in der die Nichtunterlegenheit einer verlängerten UVC-Verweildauer (bis zu 10 Tage) gegenüber dem frühen Wechsel (bis zu 5 Tage) zu einem PICC untersucht werden soll

Transfer of manualized Short Term Psychodynamic Psychotherapy (STPP) for social phobia into clinical practice: study protocol for a cluster-randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Psychodynamic psychotherapy is frequently applied in the treatment of social phobia. Nevertheless, there has been a lack of studies on the transfer of manualized treatments to routine psychodynamic practice. Our study is the first one to examine the effects of additional training in a manualized Short Term Psychodynamic Psychotherapy (STPP) procedure on outcome in routine psychotherapy for social phobia. This study is an extension to a large multi-site RCT (N = 512) comparing the efficacy of STPP to Cognitive-Behavioral Therapy (CBT) of Social Phobia.</p> <p>Methods/Design</p> <p>The manualized treatment is designed for a time limited approach with 25 individual sessions of STPP over 6 months. Private practitioners will be randomized to training in manualized STPP vs. treatment as usual without a specific training (control condition). We plan to enrol a total of 105 patients (84 completers). Assessments will be conducted before treatment starts, after 8 and 15 weeks, after 25 treatment sessions, at the end of treatment, 6 months and 12 months after termination of treatment. The primary outcome measure is the Liebowitz Social Anxiety Scale. Remission from social phobia is defined scoring with 30 or less points on this scale.</p> <p>Discussion</p> <p>We will investigate how the treatment can be transferred from a controlled trial into the less structured setting of routine clinical care. This question represents Phase IV of psychotherapy research. It combines the benefits of randomized controlled and naturalistic research. The study is genuinely designed to promote faster and more widespread dissemination of effective interventions. It will answer the questions whether manualized STPP can be implemented into routine outpatient care, whether the new methods improve treatment courses and outcomes and whether treatment effects reached in routine psychotherapeutic treatments are comparable to those of the controlled, strictly manualized treatment of the main study.</p> <p>Trial Registration</p> <p>German Clinical Trials Register (DRKS) DRKS00000570</p

Cognitive behavioural therapy in elderly type 2 diabetes patients with minor depression or mild major depression: study protocol of a randomized controlled trial (MIND-DIA)

<p>Abstract</p> <p>Background</p> <p>The global prevalence of diabetes among adults will be 6.4% in 2010 and will increase to 7.7% by 2030. Diabetes doubles the odds of depression, and 9% of patients with diabetes are affected by depressive disorders. When subclinical depression is included, the proportion of patients who have clinically relevant depressive symptoms increases to 26%. In patients aged over 65 years, the interaction of diabetes and depression has predicted increased mortality, complications, disability, and earlier occurrence of all of these adverse outcomes. These deleterious effects were observed even in minor depression, where the risk of mortality within 7 years was 4.9 times higher compared with diabetes patients who did not have depressive symptoms. In this paper we describe the design and methods of the Minor Depression and Diabetes trial, a clinical trial within the 'Competence Network for Diabetes mellitus', which is funded by the German Federal Ministry of Education and Research.</p> <p>Methods/Design</p> <p>Patients' inclusion criteria are: Type 2 diabetes mellitus, 65 to 85 years of age, 3 to 6 depressive symptoms (minor depression or mild major depression). Our aim is to compare the efficacy of diabetes-specific cognitive behavioural therapy adapted for the elderly vs. intensified treatment as usual vs. a guided self-help intervention regarding improvement of health related quality of life as the primary outcome. The trial will be conducted as a multicentre, open, observer-blinded, parallel group (3 groups) randomized controlled trial. Patients will be randomized to one of the three treatment conditions. After 12 weeks of open-label therapy in all treatment conditions, both group interventions will be reduced to one session per month during the one-year long-term phase of the trial. At the one-year follow-up, all groups will be re-examined regarding the primary and secondary parameters, for example reduction of depressive symptoms, prevention of moderate/severe major depression, improvement of glycaemic control, mortality, and cost effectiveness. Depending on additional funding, the sample will be continuously observed as a prospective cohort; the primary outcome will be changed to mortality for all subsequent follow-up measurements.</p> <p>Trial registration</p> <p>Current Controlled Trials Register (ISRCTN58007098).</p

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)