Janus Christian Jakobsen

Rigshospitalet | rigshospitalet · Copenhagen Trial Unit

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...

Background Psychotherapy for borderline personality disorder is often extensive and resource-intensive. Mentalisation-based therapy is a psychodynamically oriented treatment option for borderline personality disorder, which includes a case formulation, psychoeducation, and group and individual therapy. The evidence on short-term compared with long-...

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 Internet-b...

Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo ta...

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 Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of t...

Background and Purpose The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as comp...

Background Multiple clinical conditions are associated with cerebral hypoxia/ischaemia and thereby an increased risk of hypoxic-ischaemic brain injury. Cerebral near-infrared spectroscopy monitoring (NIRS) is a tool to monitor brain oxygenation and perfusion, and the clinical uptake of NIRS has expanded over recent years. Specifically, NIRS is used...

Background: Intensive rehabilitation of patients after severe traumatic brain injury aims to improve functional outcome. The effect of initiating rehabilitation in the early phase, in the form of head-up mobilization, is unclear. Objective: To assess whether early mobilization is feasible and safe in patients with traumatic brain injury admitted to...

Background COVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in...

Introduction Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Cont...

Background Non-suicidal self-injury (NSSI) has gained increased attention in recent years due to increased prevalence, especially among adolescents. Evidence-based interventions for NSSI are sparse. Emotion regulation individual therapy for adolescents (ERITA) is an online intervention that needs investigation. Non-randomised studies suggest ERITA...

Systematic reviews and meta-analyses (SRMAs) are increasing in popularity, but should they be used to inform clinical decision-making in anaesthesia? We present evidence that the certainty of evidence from SRMAs in anaesthesia (and in general) may be unacceptably low because of risks of bias exaggerating treatment effects, unexplained heterogeneity...

Background Existing self-management and behavioural interventions for diabetes vary widely in their content, and their sustained long-term effectiveness is uncertain. Autonomy supporting interventions may be a prerequisite to achieve ‘real life’ patient engagement and more long-term improvement through shared decision-making and collaborative goal...

Objectives In this sub-study of the ‘Paracetamol and Ibuprofen in Combination’ (PANSAID) trial, in which participants were randomised to one of four different non-opioids analgesic regimen consisting of paracetamol, ibuprofen, or a combination of the two after planned primary total hip arthroplasty, our aims were to investigate the distribution of...

Background: Non-suicidal self-injury (NSSI) has gained increased attention in recent years due to increased prevalence, especially among adolescents. Evidence-based interventions for NSSI are sparse. Emotion regulation individual therapy for adolescents (ERITA) is an online intervention that needs investigation. Non-randomised studies suggest ERITA...

Background: Non-suicidal self-injury (NSSI) has gained increased attention in recent years due to increased prevalence, especially among adolescents. Evidence-based interventions for NSSI are sparse. Emotion regulation individual therapy for adolescents (ERITA) is an online intervention that needs investigation. Non-randomised studies suggest ERITA...

Current guidelines recommend angiotensin receptor blocker neprilysin inhibitors (ARNI) (sacubitril/valsartan) as a replacement for angiotensin-converting-enzymeinhibitor (ACE-I) in heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy. The effects of ARNIs have not previously been assessed in a...

Background COVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in...

Background Multiple clinical conditions are associated with cerebral hypoxia/ischaemia and thereby an increased risk of hypoxic-ischaemic brain injury. Cerebral near-infrared spectroscopy monitoring (NIRS) is a tool to monitor brain oxygenation and perfusion, and the clinical uptake of NIRS has expanded over recent years. Specifically, NIRS is used...

Objective To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease. Methods We conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published...

Background: To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear. Methods/design: The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an...

Objectives: To study the extent of blinding in randomised clinical trials of psychological interventions and the interpretative considerations if randomised clinical trials are not blinded. Design: Retrospective study of trial reports published in six high impact factor journals within the field of psychiatry in 2017 and 2018. Setting: Trial repo...

Background: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. Methods and findings: This is the first edition of a living systematic review of randomized clinical trials comparing the effects...

Objective To assess if 12 novel circulating biomarkers, when added to ‘standard predictors’ available in general practice, could improve the 10-year prediction of cardiovascular events and mortality in patients with stable coronary heart disease. Design The patients participated as placebo receiving patients in the randomised clarithromycin for pa...

In a recent letter to the editor, a group of clinician-researchers posit that the conclusions in our published systematic review¹ on cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD) are based on inappropriate methodology. In this reply, we address the concerns expressed by Storch et al.

Importance Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and sub...

Background Existing self-management and behavioural interventions for diabetes vary widely in their content, and their sustained long-term effectiveness is uncertain. Autonomy supporting interventions may be a prerequisite to achieve ‘real life’ patient engagement and more long-term improvement through shared decision making and collaborative goal...

Background Existing self-management and behavioural interventions for diabetes vary widely in their content, and their sustained long-term effectiveness is uncertain. Autonomy supporting interventions may be a prerequisite to achieve ‘real life’ patient engagement and more long-term improvement through shared decision making and collaborative goal...

Background: COVID-19 is a rapidly spreading virus infection that has quickly caused extensive burden to individual, families, countries, and the globe. No intervention has yet been proven effective for the treatment of COVID-19. Some randomized clinical trials assessing the effects of different drugs have been published, and more are currently und...

Background and aims Elevated circulating levels of osteoprotegerin (OPG) are known to add to the prediction of cardiovascular mortality. Our objective was to clarify the long-term risk associated with serum OPG and the possible influence of diabetes and statins on OPG levels in patients with stable coronary artery disease (CAD). Methods We assesse...

Background The inflammatory biomarker YKL‐40 has previously been studied as a potential risk marker in cardiovascular disease. We aimed to assess the prognostic reclassification potential of serum YKL‐40 in patients with stable coronary artery disease. Methods and Results The main study population was the placebo group of the CLARICOR (Effect of C...

Aims The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8°C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and explo...

Background It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument’s poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depres...

Background: Acutely ill patients are at risk of stress-related gastrointestinal bleeding and prophylactic acid suppressants are frequently used. In this systematic review, we assessed the effects of stress ulcer prophylaxis (SUP) with proton pump inhibitors or histamine-2 receptor antagonists versus placebo or no prophylaxis in acutely ill hospita...

Background: The prevalence of overweight is increasing worldwide in children. Multi-component interventions incorporating diet, physical activity, and behavioural change have been shown to reduce body mass index (BMI). Whilst many children have their own smartphone, the clinical effects of using smartphone applications (apps) for overweight are un...

Background: Optimization of postoperative pain treatment is of upmost importance. Multimodal analgesia is the main postoperative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the 'DEXamethasone twice for pain treatment after TKA' trial, we aim to investigate the role of one or two doses of glucocorti...

When analysing and presenting results ofrandomised clinical trials, trialists rarely report if or how underlying statisticalassumptions were validated. To avoid data-driven biased trial results, it should be common practice to prospectively describe the assessments of underlying assumptions. In existing literature, there is no consensus onhow trial...

Introduction Retrospective studies conducted in psychiatric inpatient wards have shown a relation between the intensity of daylight in patient rooms and the length of stay, pointing to an antidepressant effect of ambient lighting conditions. Light therapy has shown a promising antidepressant effect when administered from a light box. The emergence...

Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical t...

Background: Retrospective studies conducted in psychiatric wards have indicated a shorter duration of stay for depressed inpatients in bright compared to dim daylight-exposed rooms, pointing to a possible antidepressant effect of daylight conditions. Dynamic LED lighting, aiming to mimic daylight conditions, are currently been installed in several...

Background: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment base...

Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This detailed statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation b...

Background: Cardiovascular disease is the number one cause of death globally. According to the World Health Organization, 7.4 million people died from ischaemic heart diseases in 2012, constituting 15% of all deaths. Acute myocardial infarction is caused by blockage of the blood supplied to the heart muscle. Beta-blockers are often used in patient...

Background: Hypertension, type 2 diabetes mellitus and cardiovascular disease are among the leading causes of mortality globally. Exercise is one of the commonly recommended interventions/preventions for hypertension, type 2 diabetes mellitus and cardiovascular disease. However, the previous reviews have shown conflicting evidence on the effects o...

Background: Sepsis is a major cause of morbidity and mortality among neonates and infants. Antibiotics are a central part of the first line treatment for sepsis in neonatal intensive care units worldwide. However, the evidence on the clinical effects of the commonly used antibiotic regimens for sepsis in neonates remains scarce. This systematic re...

Objective The objective of the Dutch Sildenafil therapy in dismal prognosis early onset fetal growth restriction (STRIDER) randomised clinical trial is to assess the beneficial and harmful effects of sildenafil versus placebo on fetal and neonatal mortality in pregnant women with severe early-onset fetal growth restriction. The objective of this de...

Background Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual....

Background: Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, and improving health-related quality of life. The Chinese herbal...

Background: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC-III trial is to investigate the benefits and harms of treatment based...

Introduction Fever is an integral part of the inflammatory response and has therefore likely a physiological role in fighting infections. Nevertheless, whether fever in itself is beneficial or harmful in adults is unknown. This protocol for a systematic review aims at identifying the beneficial and harmful effects of fever control interventions in...

Background: The mainstay treatment for hypoxaemia is oxygen therapy, which is given to the vast majority of adults admitted to the intensive care unit (ICU). The practice of oxygen administration has been liberal, which may result in hyperoxaemia. Some studies have indicated an association between hyperoxaemia and mortality, whilst other studies h...

Background: Heart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldoster...

Background: Haloperidol is the most frequently used drug to treat delirium in the critically ill patients. Yet, no systematic review has focussed on the effects of haloperidol in critically ill patients with delirium. Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials (RCTs) a...

Background: Despite increasing survival, cardiovascular disease remains the primary cause of death worldwide with an estimated 7.4 million annual deaths. The main symptom of ischaemic heart disease is chest pain (angina pectoris) most often caused by blockage of a coronary artery. The aim of coronary artery bypass surgery is revascularisation achi...

Disease-related mortality (eg, cardiovascular mortality or breast-cancer mortality) is often used as an outcome in randomised clinical trials and systematic reviews. The rationale why disease-related mortality might be used in addition to, or instead of, all-cause mortality seems to be that disease-related mortality may more readily detect the expe...

Objective: To assess benefits and harms of cognitive behavioral therapy (CBT) versus no intervention or versus other interventions for pediatric obsessive-compulsive disorder (OCD). Method: We searched for randomized clinical trials of CBT for pediatric OCD. Primary outcomes were OCD severity, serious adverse events, and level of functioning. Se...

Background: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and...

Introduction Pain is a frequent clinical symptom with significant impact on the patient’s well-being. Therefore, adequate pain management is of utmost importance. While cannabinoids have become a more popular alternative to traditional types of pain medication among patients, the quality of evidence supporting the use of cannabinoids has been quest...

Background Major depressive disorder is estimated by the WHO to affect more than 300 million people globally, making depression the leading cause of disability worldwide. Antidepressants are commonly used to treat depression. Objective The study aimed to provide an update on the evidence on the effects of antidepressants compared with placebo. Sho...

Background: Multimodal analgesia is considered the leading principle for postoperative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists. Aim: To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone as part of a multimodal analgesic regimen (paracetamol, NSAID and per...

Background: Chronic hepatitis B is a liver disease associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming to reduce the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, as well as to improve health-related quality of life....

Background: Psychiatric disorders are highly prevalent and associated with great symptomatic, functional, and health economic burdens. Psychotherapy is among the recommended and used interventions for most psychiatric disorders and is becoming widely accessible in mental health systems. The effects of specific forms of psychotherapy (e.g., psychod...

Background: Sepsis is a relatively common and deadly condition that constitutes a major challenge to the modern health care system. Quinolones are sometimes used in combination with beta-lactam antibiotics for sepsis, but no former systematic review has assessed the benefits and harms of quinolones in patients with sepsis. Methods: We will perfo...

In this response, we address point by point the additional issues raised by Hieronymus et al. in their second round of critique of our systematic review on selective serotonin reuptake inhibitors for major depression. We repulse that we are biased or mistaken in any major ways. We acknowledge that we missed a few small, mostly unpublished trials, a...

Background: Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may also have coinfections including HIV and other hepatitis viruses (hepatitis C or D), and coinfections may increase the risk of all-cause...

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

Objective and methods: It is rare that trialists report power estimations of non-primary outcomes. In the present article, we will describe how to define a valid hierarchy of outcomes in a randomised clinical trial, to limit problems with Type I and Type II errors, using considerations on the clinical relevance of the outcomes and power estimation...

Objectives: Risks of random type I and II errors are associated with false positive and false negative findings. In conventional meta-analyses, the risks of random errors are insufficiently evaluated. Many meta-analyses, which appear conclusive, might, in fact, be inconclusive because of risks of random errors. We hypothesize that, for interventio...

Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase...

Introduction: We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke. Patients and methods: In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were r...

Background Psychotherapy for borderline personality disorder is often lengthy and resource-intensive. However, the current length of outpatient treatments is arbitrary and based on trials that never tested if the treatment intensity could be reduced. As a result, there is insufficient evidence to inform the decision between short-term and long-term...

In order to ensure the validity of results of randomised clinical trials and under some circumstances to optimise statistical power, most statistical methods require validation of underlying statistical assumptions. The present paper describes how trialists in major medical journals report tests of underlying statistical assumptions when analysing...

Background: Hepatitis B virus (HBV) infection, a liver disease caused by hepatitis B virus, may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may have co-infections including HIV and other hepatitis viruses (hepatitis C or D), and co-infection may increase the risk of all-cause mortality. C...

Background Sepsis is the primary diagnosis in more than 8% of all critically ill children and sepsis is among the ten leading causes of death in children <10 years. Glucocorticosteroids are currently recommended in septic children with fluid or catecholamine resistant refractory shock. Glucocorticosteroids are widely used for severe sepsis in paedi...

Background Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC-III trial is to investigate the benefits and harms of treatment based...