Christian Gluud

Copenhagen Trial Unit · Centre for Clinical Intervention Research

Background Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks o...

Background Chronic pain in adults is a frequent clinical symptom with a significant impact on patient well-being. Therefore, sufficient pain management is of utmost importance. While tramadol is a commonly used pain medication, the quality of evidence supporting its use has been questioned considering the observed adverse events. Our objective will...

Background: Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal mor...

Background: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carri...

Objectives To assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients. Setting Outpatient treatment. Participants Participants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespect...

Background: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants’ lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage i...

Introduction It is essential to choose a realistic anticipated intervention effect when calculating a sample size for a randomised clinical trial. Unfortunately, anticipated intervention effects are often inflated, when compared with the ‘true’ intervention effects. This is documented for mortality in critical care trials. A similar pattern might e...

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on...

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed...

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks’ postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonata...

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours afte...

When conducting randomised clinical trials, the choice of methodology and statistical analyses will influence the results. If the planned methodology is not of optimal quality and predefined in detail, there is a risk of biased trial results and interpretation. Even though clinical trial methodology is already at a very high standard, there are man...

Background: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict ra...

Background: Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small...

Background: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on...

Background: Endoscopic retrograde cholangiography (ERC) with stone extraction and papillotomy with subsequent laparoscopic cholecystectomy-the two-step approach-is the standard treatment of common bile duct stones in many countries. However, ERC is associated with a high risk of complications and more than half of patients require multiple ERCs. M...

Background: The evidence on the effects of metformin and insulin in type 2 diabetes patients on quality of life, patient satisfaction, and cardiovascular outcomes is unclear. Methods: The Copenhagen Insulin and Metformin Therapy (CIMT) trial is an investigator-initiated multicentre, randomised, placebo-controlled trial with a 2 × 3 factorial des...

Objectives: To assess the benefits and harms of cannabinoids in participants with pain. Design: Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data sources: The Cochrane Library, MEDLINE, Embase, Science C...

Background: Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU...

Introduction Coronary artery bypass grafting can be conducted using the radial artery as a bypass graft. However, it remains unclear which harvesting method is superior, i.e. endoscopic or open radial artery, and which site for proximal anastomosis of the radial artery has the greatest benefits? Methods The NEO Trial is a single site randomised cl...

Background: Non-suicidal self-injury (NSSI) is common in adolescents receiving psychiatric treatment and is a significant risk factor for suicidal behavior. There are few randomised clinical trials assessing interventions for NSSI in youth, and knowledge about internet-delivered interventions is limited. Objective: We assessed the feasibility of...

Introduction Neurodevelopmental disorders are a group of disorders thought to be associated with the functioning of the brain and the nervous system. Children with neurodevelopmental disorders often have sleep-related comorbidities that may negatively affect quality of life for both the children and their families. Melatonin is one of the most used...

Background Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different lev...

Background: Clinical practice guidelines (CPGs) contain recommendations intended to aid clinicians in providing optimal care for patients and should be derived from the best quality evidence available. The highest quality evidence is obtained through systematic reviews using Cochrane methodology. This exploratory study aimed to determine the propor...

Background Deep brain stimulation has been used since the 1980s for neurological disorders and the USA and Europe have now approved it for Parkinson’s disease, essential tremor, dystonia, and epilepsy. Previous reviews have assessed the effects of deep brain stimulation on different neurological disorders. These reviews all had methodological limit...

Background Autonomy supporting interventions, such as self-determination theory and guided self-determination interventions, may be a prerequisite to achieve long-term improvements in people with diabetes. Such interventions have never been systematically reviewed assessing benefits and harms and controlling the risks of random errors using trial s...

Background Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder which affects up to 3% of children and adolescents. OCD in children and adolescents is generally treated with cognitive behavioural therapy (CBT), which, in more severely affected patients, can be combined with antidepressant medication. The TECTO trial aims to co...

Background: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of go...

Objective To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. Design Systematic review and network meta-analysis. Data sources Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries,...

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of liver support systems for adults with acute liver failure. Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Introduction Coronary artery bypass grafting can be conducted using the radial artery as a bypass graft. However, it remains unclear, which harvesting method is superior, i.e. endoscopic or open radial artery, and which site for proximal anastomosis of the radial artery has the greatest benefits? Methods The NEO Trial is a single site randomised cl...

Background: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. Methods: We conducted a systematic review with...

Background Adequately conducted systematic reviews with meta-analyses are considered the highest level of evidence and thus directly defines many clinical guidelines. However, the risks of type I and II errors in meta-analyses are substantial. Trial Sequential Analysis is a method for controlling these risks. Erroneous use of the method might lead...

Objectives To assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development. Design Systematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Recommendations Assessment, Development and Evalua...

Background: Control interventions in randomised trials provide a frame of reference for the experimental interventions and enable estimations of causality. In the case of randomised trials assessing patients with mental health disorders, many different control interventions are used, and the choice of control intervention may have considerable imp...

Purpose: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the inte...

Abstract Background Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions rega...

The risks of type I and type II errors are often not considered in systematic reviews and meta-analyses, especially the errors due to too few data or due to repetitive meta-analysis during updates. Turner et al. showed that 70% of all Cochrane reviews had less than 50% power in their analysis to detect a 30% relative risk reduction leading to subst...

Background Cerebral oxygenation monitoring utilising near-infrared spectroscopy (NIRS) is increasingly used to guide interventions in clinical care. The objective of this systematic review with meta-analysis and Trial Sequential Analysis is to evaluate the effects of clinical care with access to cerebral NIRS monitoring in children and adults versu...

Background COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Methods and findings Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL...

Background Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this con...

Background Data monitoring of clinical trials is a tool aimed at reducing the risks of random errors (e.g. clerical errors) and systematic errors, which include misinterpretation, misunderstandings, and fabrication. Traditional ‘good clinical practice data monitoring’ with on-site monitors increases trial costs and is time consuming for the local i...

Introduction In the management of type 2 diabetes, autonomy-supporting interventions may be a prerequisite to achieving more long-term improvement. Preliminary evidence has shown that the guided self-determination (GSD) method might have an effect on haemoglobin A1c and diabetes distress in people with type 1 diabetes. Previous trials were at risk...

Background: Subarachnoid haemorrhage has an incidence of up to nine per 100,000 person-years. It carries a mortality of 30% to 45% and leaves 20% dependent in activities of daily living. The major causes of death or disability after the haemorrhage are delayed cerebral ischaemia and rebleeding. Interventions aimed at lowering blood pressure may re...

Objectives To assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure. Design A systematic review with meta-analysis and trial sequential analysis. Eligibility criteria Randomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants wi...

Introduction Intensive care for patients with severe acute brain injury aims both to treat the immediate consequences of the injury and to prevent and treat secondary brain injury to ensure a good functional outcome. Sedation may be used to facilitate mechanical ventilation, for treating agitation, and for controlling intracranial pressure. Ketamin...

PurposeWe compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bay...

Background: Cardiovascular disease is the number one cause of death globally. According to the World Health Organization (WHO), 7.4 million people died from ischaemic heart disease in 2012, constituting 15% of all deaths. Beta-blockers are recommended and are often used in patients with heart failure after acute myocardial infarction. However, it...

Background Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up...

Formation of reactive oxygen species has been linked to the development of diabetes complications. Treatment with metformin has been associated with a lower risk of developing diabetes complications, including when used in combination with insulin. Metformin inhibits Complex 1 in isolated mitochondria and thereby decreases the formation of reactive...

In the age of information technology development, healthcare professionals around the world have the opportunity to simultaneously access advanced scientific developments, modern achievements, and the results of new clinical trials. The clinical guidelines of the international medical communities are based on the results of meta-analyses of clinica...

Background: Adequately conducted systematic reviews with meta-analyses are considered the highest level of evidence and thus directly defines many clinical guidelines. However, the risk of type I and II errors in meta-analyses are substantial. Trial Sequential Analysis is a method for controlling these risks. Erroneous use of the method might lead...

Background Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect...

Objectives To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker’s clinical utility requires c...

Objective: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in increasing proportions of children and adolescents. The psychostimulant methylphenidate has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years. Considering recent publications...

Background: Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases. Objectives: To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases. Search methods: We searched the C...

Background Non-suicidal self-injury (NSSI) has a lifetime prevalence of 17% in adolescents in the general population and up to 74% in adolescents with psychiatric disorders. NSSI is one of the most important predictors of later suicidal behaviour and death by suicide. The TEENS feasibility trial was initiated to assess the feasibility and safety of...

Background Major depression significantly impairs quality of life, increases the risk of suicide, and poses tremendous economic burden on individuals and societies. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed antidepressant. The effects of duloxetine have, however, not been sufficiently assessed in earlier syst...

Background In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred...