Per Winkel

Copenhagen Trial Unit

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...

Background: Internet-based cognitive behavioural self-help psychotherapy (ICBT) can be an important alternative or supplement to ordinary face-to-face therapy. Aim: To assess effectiveness of ICBT for adults with an anxiety disorder. Methods: Sixty-four participants were randomised to 9 weeks with the FearFighter ICBT program (n = 32) or no interve...

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...

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...

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: We aimed to describe the exposure to blood transfusions and mortality among patients with septic shock. Methods: We did a retrospective cohort study of two cohorts - patients with septic shock registered in a Danish ICU database (2008-2010) and patients from the Transfusion Requirements in Septic Shock (TRISS) trial (2011-2013). We e...

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...

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...

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...

Current guidelines advocate to limit red-cell transfusion during surgery, but the feasibility and safety of such strategy remains unclear as the majority of evidence is based on postoperative stable patients. We assessed the effects of a protocol aiming to restrict red-cell transfusion throughout hospitalization for vascular surgery. Fifty-eight pa...

BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain. METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial...

Background Sexual dysfunction is common in patients with either ischaemic heart disease (IHD) or implantable cardioverter defibrillator (ICD) and has a negative impact on quality of life. Non-pharmacological treatment options are lacking. The purpose of this trial was to assess the effect of sexual rehabilitation versus usual care for males with er...

Objective To characterise the long-term prognosis of patients with stable coronary artery heart disease by means of ‘standard predictors’ defined as demographic, clinical and biochemical quantities routinely available in general practices and ascertained at an interview not prompted by renewed cardiac complaints. Methods This is an observational s...

Background and aims: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. Methods: The CLARICOR trial is a randomised,...

Background: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease. Methods and results: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Dise...

Table S1. Standard Predictors Adjusted for in Model D Table S2. Logistic Regression Analyses for Outcomes That Violated the Proportional Hazard Assumption for Age for the Fully Adjusted Model (model D) Table S3. Accelerated Failure Regression Analyses for Outcomes That Violated the Proportional Hazard Assumption for Age for the Fully Adjusted Mod...

Objectives: Rehabilitation of patients following coronary artery bypass grafting (CABG) has been widely studied; however, research into early rehabilitation after CABG is sparse. The aim of this trial was to assess the impact of early rehabilitation, compared with usual care in patients following CABG. Design: Randomized controlled trial. Patie...

Background Missing data may seriously compromise inferences from randomised clinical trials, especially if missing data are not handled appropriately. The potential bias due to missing data depends on the mechanism causing the data to be missing, and the analytical methods applied to amend the missingness. Therefore, the analysis of trial data with...

Background Cooling may reduce infarct size and improve neurological outcomes in patients with ischaemic stroke. In phase II trials, cooling awake patients with ischaemic stroke has been shown to be feasible and safe, but the effects in functional outcomes has not yet been investigated in an adequately sized randomised clinical trial. Methods/desig...

Objective Occupational hand eczema has adverse health and socioeconomic impacts for the afflicted individuals and society. Prevention and treatment strategies are needed. This study aimed to assess the effectiveness of an educational intervention on sickness absence, quality of life and severity of hand eczema. Methods PREVEX (PreVention of EXema)...

Background Sickness absence in hand eczema patients has been associated with stress rather than disease severity, indicating that personal aspects regarding hand eczema should be investigated further. Objectives To examine whether patient education vs treatment as usual can influence behaviour and knowledge regarding skin protection and care, as w...

Background: Head-to-head trials to guide antipsychotic treatment choices for paediatric psychosis are urgently needed because extrapolations from adult studies might not be implementable. In this superiority trial with two-sided significance testing, we aimed to compare the efficacy and safety of quetiapine-extended release (quetiapine-ER) versus...

Prospective parents widely use education to gain information about, e.g., labour and parenting skills. It is unknown if antenatal education in small classes is more beneficial for parenting stress and parenting alliance compared with other types of antenatal education. In the present randomised trial, we examined the effect of antenatal education i...

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Background The purpose of the predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC) study is exploratory and hypothesis generating. We want to identify biochemical quantities which—conditionally on the values of available standard demographic, anamnestic, and biochemical data—may improve the prediction of cardiovas...

Objective: To investigate the effect of client feedback in group psychotherapy on attendance and treatment outcome for patients with eating disorders. Method: We conducted a randomized clinical trial with central randomization stratified for diagnosis and treatment type according to a computer-generated allocation sequence concealed to the inves...

Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome w...

The SafeBoosC Phase II protocol. (PDF)

Consort 2010 Checklist. (DOC)

Introduction Patients undergoing coronary artery bypass graft surgery often experience a range of symptoms. Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation have a positive physiological and psychological effect in early outpatient rehabilitation. The SheppHeartCABG trial will investigate the eff...

Background: Internet-based self-help psychotherapy (IBT) could be an important alternative or supplement to ordinary face-to-face therapy. The findings of randomised controlled trials indicate that the effects of various IBT programmes for anxiety disorders seem better than no intervention and in some instances are equivalent to usual therapy. In...

PurposeWe assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock. Methods We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction gro...

Purpose: We assessed the predefined long-term outcomes in patients randomised in the Transfusion Requirements in Septic Shock (TRISS) trial. Methods: In 32 Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin of 9 g/dl or less to receive single units of leuko-reduced red cells when haemoglobin level was 7 g/dl or less...

Background: To assess the effects of comprehensive cardiac rehabilitation compared with usual care on physical activity and mental health for patients treated with catheter ablation for atrial fibrillation. Methods: The patients were randomized 1:1 stratified by paroxysmal or persistent atrial fibrillation and sex to cardiac rehabilitation consi...

Objective To examine the effect of an antenatal education programme in small classes versus standard auditorium-based lectures. Design Randomised trial using random-generated web-based 1:1 allocation. Setting The largest birth site in the Capital Region of Denmark, from August 2012 to May 2014. Participants 1766 pregnant women. Inclusion criteria ≥...

Background Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed as first-line drugs for the treatment of depression. However, the mechanisms of action for SSRIs are unclear and besides neurotransmitter modulation may depend on modulation of the hypothalamic-pituitary-adrenal (HPA) system. The glucocorticoid receptor (GR) isoform α...

Background: The SafeBoosC phase II multicentre randomised clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline versus no NIRS-data and treatment as usual in the control group during the first 72 hours of life. The trial demonst...

Objective: Brain-derived neurotrophic factor (BDNF) seems to play an important role in the course of depression including the response to antidepressants in patients with depression. We aimed to study the effect of an antidepressant intervention on peripheral BDNF in healthy individuals with a family history of depression. Methods: We measured c...

Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However, no randomized clinical trials have tested a comprehensive reha...

We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised to prolonged-release melatonin 2 mg daily versus matching placebo and were c...

Choosing the best model for analysis of count data in randomised clinical trials is complicated. In this paper, we review count data analysis with different parametric and non-parametric methods used in randomised clinical trials, and we define procedures for choosing between the two methods and their subtypes. We focus on analysis of simple count...

Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 20...

Background and aims Extremely preterm infants have a high risk of moderate to severe long-term neurodevelopmental impairment. Hypoxic or hyperoxic brain injury may be a contributing factor. The SafeBoosC trial investigated if it is possible to stabilise the cerebral oxygenation of extremely preterm infants. Methods This was a phase II randomised, s...

Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. Methodologies for assessing statistical and clinical significance of interventio...

Background: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. Methods: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin c...

Background: Providing care for adolescents with type 1 diabetes is complex, demanding, and often unsuccessful. Guided self-determination (GSD) is a life skills approach that has been proven effective in caring for adults with type 1 diabetes. To improve care, GSD was revised for adolescents, their parents, and interdisciplinary healthcare provider...

Objective: To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants. Setting: The trial was conducted at an outpatient psychiatric clinic for non-psychotic patients in Roskilde, Denmark. Participants: 44 consecutive adult participants diagnosed with major d...

Objectives: To elucidate the prognostic power of serum osteoprotegerin (OPG) in patients with stable coronary artery disease (CAD). Methods: Serum OPG levels were measured in the CLARICOR trial cohort of 4063 patients with stable CAD on blood samples drawn at randomization. The follow-up was 2.6 years for detailed cardiovascular events and 6 yea...

Rationale Cooling reduced infarct size and improved neurological outcomes in animal studies modeling ischemic stroke, and also improved outcome in randomized clinical trials in patients with hypoxic-ischemic brain injury after cardiac arrest. Cooling awake patients with ischemic stroke has been shown feasible in phase II clinical trials. Primary a...

We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate. This was an investigator-initiated, parallel-grouped, blinded randomised trial using computer-generated allocation sequence and centralised allocation data that included 804 patients with severe sepsis...

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Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alterna...

Objective: To investigate the effects of social-skills training and a parental training program on children with ADHD as measured by the children's attachment competences. Method: The SOSTRA trial is a randomized, parallel-group, outcome-assessor-blinded, superiority trial evaluating 8 weeks social-skills training and parental training plus stan...

Aims:The aim of this randomised clinical trial was to assess a comprehensive cardiac rehabilitation intervention including exercise training and psycho-education vs 'treatment as usual' in patients treated with an implantable cardioverter defibrillator (ICD).Methods:In this study 196 patients with first time ICD implantation (mean age 57.2 (standar...

Serious illness will inevitably lead to a fundamental emotional reaction. Traditionally, in interventional treatment or rehabilitation trials, the psychological status of patients with implantable cardioverter defibrillators has been evaluated with anxiety and depression as outcome measures. In caring for these patients, the aim of nursing is to he...

Background: Instructor feedback reduces the number of repetitions and time to reach proficiency during laparoscopic simulator training. The objective of this study was to examine the effect of instructor feedback on long-term skill retention. Methods: A 6-month follow-up of a randomized trial. Participants were surgical novices (medical students...

The incidence of occupational hand eczema is approximately 0.32 per 1,000 person years. The burden of the disease is high, as almost 60% has eczema-related sick leave during the first year after notification, and 15% are excluded from the workforce 12 years after disease onset. New treatments and prevention strategies are needed.Methods/design: Tri...

Background: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temper...

Sexuality is an important part of people's physical and mental health. Patients with heart disease often suffer from sexual dysfunction. Sexual dysfunction has a negative impact on quality of life and well-being in persons with heart disease, and sexual dysfunction is associated with anxiety and depression. Treatment and care possibilities seem to...

We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES). In post hoc analyses, we examined the associations between fluid assignment, hemostatic variables, bleeding events, transfusions, and death among 798 patients with severe sepsis randomized to fluid resuscitation with HES 130/0...

Objectives To examine the efficacy and cost-effectiveness of group based antenatal education for improving childbirth and parenting resources compared to auditorium based education. Methods Participants: 2350 Danish pregnant women and their partners ⩾18 years old, recruited before 20 + 0 gestational weeks. Population-based individually randomised...

Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups...

Aims: Low prevalence of detectable cardiac troponin in healthy people and low-risk patients previously curtailed its use. With a new high-sensitive cardiac troponin assay (hs-cTnT), concentrations below conventional detection may have prognostic value, notably in combination with N-terminal pro-B-type natriuretic peptide (NT-pro-BNP). Methods and...

Background Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to exam...

OBJECTIVE: To investigate the impact of instructor feedback versus no instructor feedback when training a complex operational task on a laparoscopic virtual reality simulator. BACKGROUND: Simulators are now widely accepted as a training tool, but there is insufficient knowledge about how much feedback is necessary, which is useful for sustainable i...

Background: Graves' hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects on autoimmune hypothyroidism and on Gra...

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment o...