Center for Klinisk Forskning

Principal investigator: Julie Kristine Knudsen
Supervisors: Suzette Sørensen (Main supervisor), René Ernst Nielsen (Co-supervisor) and Simon Hjerrild (Co-supervisor)

Depression is a complex psychiatric disease with both mental, cognitive, emotional and somatic symptoms. Many patients have gastrointestinal issues, which there does not appear to be any medical reasons for. One hypothesis is that intestinal bacteria, known as the gut microbiota, in patients with depression may be involved in the pathology, and this may be the reason why they suffer from gastrointestinal symptoms. Antidepressant treatments have antibacterial properties, which may be why the gastrointestinal issues resolve, and the symptoms are alleviated on antidepressant medication, other than its neurological effects.

This Ph.D. project wished to establish if the effect of antidepressants on patients with depression can be associated with the loss or gain of specific gut bacteria. The project is split in a clinical and a preclinical part.

The clinical part of the study focussed on patients with depression. Newly diagnosed, antidepressant treatment-naïve patients aged 18-24 were recruited from the psychiatric departments of Aalborg University Hospital and Horsens Regional Hospital. Simultaneously, healthy controls aged between 18-30 were recruited through the North Denmark Regional Hospital. These participants were followed for twelve weeks, where they delivered faecal and blood samples at baseline, four and twelve weeks. Patients were instructed to begin antidepressant treatment after collection of the baseline sample. Additionally, all participants fulfilled questionnaires about their mental wellbeing, dietary habits, and gastrointestinal symptoms.

The preclinical part of the study focussed on the development of depressive-like behaviour in rats. Faecal samples collected from patients and healthy individuals was transplanted into rats to evaluate whether the bacteria could induce depressive-like behavior. Animals underwent behavioural analyses, and was then euthanised for tissue collection.

The project was finalized in the end of 2020, and the data is currently being analysed.

Ph.d. student, MSc.med. Caspar Bundgaard-Nielsen
Supervisors: Suzette Sørensen, Mette Nyegaard, Søren Hagstrøm

Background and aim

The neurodevelopmental disorders Attention Deficit Hyperactivity Disorder (ADHD) and autism spectrum disorder is common childhood disorders, with potentially severe social and emotional outcomes. While both disorders have clear genetic involvement, genetics alone fails to accurately predict the risk of the disorders, and thus external factors are believed to be involved. For both disorders, gastrointestinal problems like constipation and stomach pain are common, suggesting an involvement of the gut in the disorders.

The human gastrointestinal tract is known to contain several bacteria, termed the gut microbiota. These bacteria are involved in several normal functions of the body, and thus disturbances of the gut microbiota have been linked to several disorders. Lately, studies have revealed a bidirectional interaction between the gut microbiota and the brain. This gut-brain axis has been shown to be affected in both ADHD and autism, suggesting that the gut microbiota may be an important component. The exact microbial composition associated with these disorders are poorly described, while the mechanisms by which these bacteria can affect the brain and thus play a role in ADHD and autism are unclear.

The aim of this project is, to describe the gut microbiota associated with ADHD and autism, as well as how these bacteria influence the immune system of the affected children. Secondly, since both ADHD and autism have a high degree of comorbidity, we plan to compare the two disorders with each other, to examine whether the same variations are behind both disorders.

Methods

To this end, we have invited children diagnosed with ADHD and/or autism to participate in the study. As controls, we have included non-affected siblings or non-related children. The families were invited through the Child Psychiatric Department at Aalborg University Hospital, as well as through social medias and patient organizations.

All children delivered fecal, urine and blood samples, with the following purpose:

• Fecal samples were used for investigating the microbiota composition, using a technique known as 16S ribosomal RNA gene sequencing. This technique allows us to describe the bacterial composition of the gut.
• Blood samples are used to investigate immune signals, genetic involvement as well as to test for the presence of gut microbiota products in the blood. This allows us to investigate whether the immune system is becoming excessively active in ADHD and autism, and how the gut microbiota may impact this.
• Finally, urine samples are used to measure the level of the stress hormone cortisol.

Time schedule

The study is running in the period September 1^st, 2017 and is expected to finish August 31^st, 2021. Recruitment of study participants was initiated January 2018 and ended during the spring of 2020. Currently, the data is being analyzed and articles are being finalized. 

Ph.D. student, MD, Mette Krogh Pedersen
Supervisors: Steen Kåre Fagerberg, Mads Lumholdt, Søren Mikkelsen, Kjeld Damgaard, Peter Leutscher

Background

Aim

To examine a specific hospital-used blood sample for additional use in the prehospital setting. More specified, the project examines the quality and stability of the venous blood gas sample and its feasibility within the prehospital work scene.   

Method

The project includes three clinical studies. One study focuses on time delay and cooling in a controlled hospital setting and includes critical ill patients admitted to the intensive care unit (ICU). The following two studies focus on the prehospital environment and include transport by either ambulance or helicopter. The prehospital studies include critical ill or injured patients assisted by a mobile emergency care unit (MECU) or the helicopter emergency medical service (HEMS). Samples are analysed using i-STAT (Abbott, USA) or ABL90/800 FLEX (Radiometer, Denmark) for pH, pCO2, pO2, HCO3, lactate, glucose, haemoglobin and potassium. We combine all analyses into a general evaluation of the venous blood gas sample.

Time plan

The data collection of the study that includes ICU patients ended January 2021, we expect to present the result spring 2021. The two studies in collaboration with the MECU and HEMS are in the start-up phase and partly on pause because of the COVID-19 situation. Data collection is expected to be carried out during 2021. The overall PhD project will end winter/spring 2023.

Ninna Rysholt Poulsen, PhD-student, MSc.
Supervisors: Peter Leutscher, Professor, PhD, MD; Mona Kyndi Pedersen PhD, MSc, RN; Morten Breinholt Søvsø, PhD, MD; Liv Marit Valen Schougaard, PhD, MSc, RN.

Background

Patient Reported Outcome Measures (PROM) collected by means of a questionnaire may provide a unique opportunity to obtain and document more complete health-related information directly from the patient. As a result, the communication could be improved and add to shared decision-making between the patient and the healthcare professionals. Further, the clinical assessment and interpretative evaluation of signs and symptoms may turn out more valid.

Aim and method

The aim of the project is to develop, validate and evaluate the clinical use of a PROM based questionnaire, named PROMED. PROMED is intended to individualize and optimize the care for the patients in the ED.

The specific objective is to develop the PROMED questionnaire which will be given to the patients when they are admitted to the ED. The collected health-related information will be sent directly to the electronic patient journal and be used by physicians and nurses prior to the consultation with the patient.

Following the development of the PROMED questionnaire, it will be tested for feasibility and finally evaluated in a pragmatic RCT-study. The hypothesis is that PROMED will increase patient satisfaction, decrease non-specific diagnoses and proportion of re-admittances.

Time schedule

Rune Sejer Jakobsen, Cand.Polyt. in Biomedical Engineering and Informatics, Ph.D. student
Supervisors: Peter Leutscher, Centre for Clinical Research, Kristoffer Koch, Department of Infectious Diseases, Aalborg University Hospital, Thomas Dyhre Nielsen, Aalborg University, Institute for Computer Science

Background

Hospital-acquired infections (HAI) remain the most common adverse outcome within a hospital setting. Management of HAI is complex and relies on proper hygienic preventive measures and treatment with antibiotic therapy. To assist in the complex HAI management, we develop models from machine learning for early and accurate identification of patients at high risk of acquiring HAI. ML enables the utilization of patterns from huge datasets, hence big data, which also enables predictions and classification of patients at risk of experiencing HAI. We also sought to address dimensions of interpretability. Our models may lead to targeted prevention measures in the future.

The project includes a collaboration between the Centre for Clinical Research at North regional Hospital, the Business Intelligence Unit (BI) in the North region of Denmark and the Institute for Datalogi at Aalborg University.

Regionshospital Nordjylland har en vigtig opgave indenfor den kliniske misbrugstestning. Klinisk Biokemisk afdeling har et af landets førende hospitalslaboratorier, når det gælder udbuddet af analyser og support til rekvirenter af misbrugsanalyser. Ledende overlæge Peter Hindersson og Hospitalskemiker Torben Breindahl har ansvaret for disse aktiviteter. De anvendte analyseteknikker er primært højtryksvæskekromatografi og gaskromatografi koblet til massespektrometre (HPLC-MS, GC-MS).

Forbundet hermed er en række udviklings- og forskningsområder, hvor misbrugslaboratoriet har gjort sig gældende. Det har tidligere omfattet analyse af nye psykoaktive stoffer og undersøgelse af hvorvidt deres metabolitter kan benyttes som potentielle biomarkører. Laboratoriet råder også over validerede metoder til bestemmelse af cannabinoider i serum og urin. Disse metoder anvendes i øjeblikket til forskningsformål, bl.a. inden for medicinsk Cannabis. Herudover er laboratoriet aktiv i debatten om patientsikkerhed i misbrugstestningen, som indeholder en række risici for de testede borgere, i form af fejlfortolkninger og manglende, specifik lovgivning på området.

Det er misbrugslaboratoriets vision for fremtiden at kunne tilbyde et ph.d. studium i analytisk, kliniske misbrugsanalyser, og udvikle værktøjer til forskning i prævalensen for nye psykoaktive stoffer i sårbare miljøer, såsom psykiatrien. Projektpartnere er derfor velkomne til at kontakte afdelingen med henblik på tværfagligt samarbejde.