Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

Background: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment.

Algorithm-based modular psychotherapy vs. cognitive-behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof-of-concept randomized controlled trial.

Effect sizes of psychotherapies currently stagnate at a low-to-moderate level. Personalizing psychotherapy by algorithm-based modular procedures promises improved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular-based psychotherapy, using a personalized treatment algorithm, is lacking.

Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials.

Importance: For the large population of people with drug-refractory epilepsy, alternative treatment approaches are needed. Clinical trial outcomes of a novel stimulation device, which is newly available in Europe for the treatment of patients with a predominant seizure focus, are reported for the first time.

Objective: To perform a pooled analysis of the results of 2 prospective, multicenter, single-arm trials, A Pilot Study to Assess the Feasibility of Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (EASEE II) and A Pilot Study to Assess the Feasibility of Patient-Controlled Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (PIMIDES I), assessing the safety and efficacy of epicranial focal cortex stimulation (FCS) with a novel implantable device (EASEE [Precisis]) as adjunctive treatment for adult patients with drug-refractory focal epilepsy.

Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? - Additional clinical and neuroimaging evidence.

Background: Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution.

Objective: Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape.

Study Protocol for a Randomised Controlled Trial on Pulmonary Metastasectomy vs. Standard of Care in Colorectal Cancer Patients With ≥ 3 Lung Metastases (PUCC-Trial).

This is a multicentre prospective randomised controlled trial for patients with 3 or more resectable pulmonary metastases from colorectal carcinoma. The study investigates the effects of pulmonary metastasectomy in addition to standard medical treatment in comparison to standard medical treatment plus possible local ablative measures such as SBRT. This trial is intended to demonstrate an overall survival difference in the group undergoing pulmonary metastasectomy.

Modular-based psychotherapy (MoBa) versus cognitive-behavioural therapy (CBT) for patients with depression, comorbidities and a history of childhood maltreatment: study protocol for a randomised controlled feasibility trial.

Introduction: In depression treatment, most patients do not reach response or remission with current psychotherapeutic approaches. Major reasons for individual non-response are interindividual heterogeneity of etiological mechanisms and pathological forms, and a high rate of comorbid disorders. Personalised treatments targeting comorbidities as well as underlying transdiagnostic mechanisms and factors like early childhood maltreatment may lead to better outcomes.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

Objective: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET).

Materials And Methods: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation.

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial.

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose-response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

Background: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing.

Derivo embolization device in the treatment of unruptured intracranial aneurysms: a prospective multicenter study.

Background: Flow diverters (FD) are used regularly for the endovascular treatment of unruptured intracranial aneurysms. We aimed to assess the safety and effectiveness of the Derivo embolization device (DED) with respect to long-term clinical and angiographic outcomes.

Methods: A prospective multicenter trial was conducted at 12 centers.

Interpersonal Psychotherapy vs. Treatment as Usual for Major Depression Related to Work Stress: A Pilot Randomized Controlled Study.

Depressive disorders are among the leading causes of sick leave and long-term work incapacity in most modern countries. Work related stress is described by patients as the most common context of depression. It is vital to know what types of treatments are effective in improving work related problems and occupational health.

The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series.

Introduction: Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained.

Individualised stepwise adaptive treatment for 3-6-year-old preschool children impaired by attention-deficit/hyperactivity disorder (ESCApreschool): study protocol of an adaptive intervention study including two randomised controlled trials within the consortium ESCAlife.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a psychosocially impairing and cost-intensive mental disorder, with first symptoms occurring in early childhood. It can usually be diagnosed reliably at preschool age. Early detection of children with ADHD symptoms and an early, age-appropriate treatment are needed in order to reduce symptoms, prevent secondary problems and enable a better school start.

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression.

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported.

Objective: To give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD.

Combination of CT angiography and MRI in surgical planning of deep brain stimulation.

Purpose: For safe deep brain stimulation (DBS) planning, an accurate visualization and localization of vessels is mandatory. Contrast enhanced (ce) MRI depicts both arteries and veins. Computed tomography angiography (CTA) detects arteries with high geometric accuracy.

ESCAlate - Adaptive treatment approach for adolescents and adults with ADHD: study protocol for a randomized controlled trial.

Background: Over the last decade, a wide range of attention-deficit/hyperactivity disorder (ADHD) treatment approaches for adults, including both pharmacological interventions and psychosocial treatments, have been proposed and observed to be efficient. In practice, individual treatment concepts are based on results of clinical studies as well as international guidelines (NICE Guidelines) that recommend a step-by-step treatment approach. Since the evidence supporting this approach is limited, the aim of the present study is to determine an optimal intervention regarding severity levels of ADHD symptomatology conducting a randomized controlled trial.

Individualised short-term therapy for adolescents impaired by attention-deficit/hyperactivity disorder despite previous routine care treatment (ESCAadol)-Study protocol of a randomised controlled trial within the consortium ESCAlife.

Background: Despite the high persistence rate of attention-deficit/hyperactivity disorder (ADHD) throughout the lifespan, there is a considerable gap in knowledge regarding effective treatment strategies for adolescents with ADHD. This group in particular often shows substantial psychosocial impairment, low compliance and insufficient response to psychopharmacological interventions. Effective and feasible treatments should further consider the developmental shift in ADHD symptoms, comorbidity and psychosocial adversity as well as family dysfunction.

One Pass Thalamic and Subthalamic Stimulation for Patients with Tremor-Dominant Idiopathic Parkinson Syndrome (OPINION): Protocol for a Randomized, Active-Controlled, Double-Blinded Pilot Trial.

Background: Besides fluctuations, therapy refractory tremor is one of the main indications of deep brain stimulation (DBS) in patients with idiopathic Parkinson syndrome (IPS). Although thalamic DBS (ventral intermediate nucleus [Vim] of thalamus) has been shown to reduce tremor in 85-95% of patients, bradykinesia and rigidity often are not well controlled. The dentato-rubro-thalamic tract (DRT) that can directly be targeted with special diffusion tensor magnetic resonance imaging sequences has been shown as an efficient target for thalamic DBS.

ESCAschool study: trial protocol of an adaptive treatment approach for school-age children with ADHD including two randomised trials.

Background: The ESCAschool study addresses the treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) in a large multicentre trial. It aims to investigate three interrelated topics: (i) Clinical guidelines often recommend a stepped care approach, including different treatment strategies for children with mild to moderate and severe ADHD symptoms, respectively. However, this approach has not yet been empirically validated.

Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy.

Background And Purpose: New deep brain stimulation leads with electrode contacts that are split along their circumference allow steering of the electrical field in a predefined direction. However, imaging-assisted directional stimulation requires detailed knowledge of the exact orientation of the electrode array. The purpose of this study was to evaluate whether this information can be obtained by rotational 3D fluoroscopy.

Modeling Variables With a Spike at Zero: Examples and Practical Recommendations.

In most epidemiologic studies and in clinical research generally, there are variables with a spike at zero, namely variables for which a proportion of individuals have zero exposure (e.g., never smokers) and among those exposed the variable has a continuous distribution.

Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT): Study Protocol of a Randomized Controlled Feasibility Trial.

Background: Essential tremor is a movement disorder that can result in profound disability affecting the quality of life. Medically refractory essential tremor can be successfully reduced by deep brain stimulation (DBS) traditionally targeting the thalamic ventral intermediate nucleus (Vim). Although this structure can be identified with magnetic resonance (MR) imaging nowadays, Vim-DBS electrodes are still implanted in the awake patient with intraoperative tremor testing to achieve satisfactory tremor control.