| 1. |
- Friesgaard, Kristian Dahl, et al.
(författare)
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Opioids for Treatment of Pre-hospital Acute Pain : A Systematic Review
- 2022
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Ingår i: Pain and Therapy. - : Springer. - 2193-8237 .- 2193-651X. ; 11:1, s. 17-36
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Forskningsöversikt (refereegranskat)abstract
- Introduction Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. Methods The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. Results A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. Conclusions Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.
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| 2. |
- Sandberg, Marten, et al.
(författare)
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Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm
- 2020
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 10:11
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Forskningsöversikt (refereegranskat)abstract
- BackgroundFew publications have addressed prehospital use of ketamine in analgesic doses. We aimed to assess the effect and safety profile of ketamine compared with other analgesic drugs (or no drug) in adult prehospital patients with acute pain.MethodsA systematic review of clinical trials assessing prehospital administration of ketamine in analgesic doses compared with other analgesic drugs or no analgesic treatment in adults. We searched PubMed, EMBASE, Cochrane Library and Epistemonikos from inception until 15 February 2020, including relevant articles in English and Nordic languages. We used the Cochrane and Grading of Recommendations Assessment, Development and Evaluation methodologies and exclusively assessed patient-centred outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias.ResultsWe included eight studies (2760 patients). Ketamine was compared with various opioids given alone, and intranasal ketamine given with nitrous oxide was compared with nitrous oxide given alone. Four randomised controlled trials (RCTs) and one cluster randomised trial included 699 patients. One prospective cohort included 27 patients and two retrospective cohorts included 2034 patients. Five of the eight studies had high risks of bias. Pain score with ketamine is probably lower than after opioids as demonstrated in a cluster-RCT (308 patients) and a retrospective cohort (158 patients) study, Delta visual analogue scale -0.4 (-0.8 to 0.0) and Delta numeric pain rating scale -3.0 (-3.86 to -2.14), respectively. Ketamine probably leads to less nausea and vomiting (risk ratio (RR) 0.24 (0.11 to 0.52)) but more agitation (RR 7.81 (1.85 to 33)) than opioids.ConclusionsThis systematic literature review finds that ketamine probably reduces pain more than opioids and with less nausea and vomiting but higher risk of agitation. Risk of bias in included studies is high.OtherScandinavian society of anaesthesiology and intensive care medicine funded meetings and software. The Norwegian Air Ambulance Foundation funded publication. Otherwise this research received no grant from any agency in the public, commercial or not-for-profit sectors.PROSPERO registration numberCRD42018114399.
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| 3. |
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| 4. |
- Arvidsson, Per I., et al.
(författare)
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Institutional profile : the national Swedish academic drug discovery & development platform at SciLifeLab
- 2017
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Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 3:2
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.
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| 5. |
- Arvidsson, Per I., et al.
(författare)
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Open for collaboration : an academic platform for drug discovery and development at SciLifeLab
- 2016
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:10, s. 1690-1698
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Forskningsöversikt (refereegranskat)abstract
- The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.
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| 6. |
- Chivukula, Indira V, et al.
(författare)
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Decoding breast cancer tissue-stroma interactions using species-specific sequencing.
- 2015
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Decoding transcriptional effects of experimental tissue-tissue or cell-cell interactions is important; for example, to better understand tumor-stroma interactions after transplantation of human cells into mouse (xenografting). Transcriptome analysis of intermixed human and mouse cells has, however, frequently relied on the need to separate the two cell populations prior to transcriptome analysis, which introduces confounding effects on gene expression.
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| 7. |
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| 8. |
- Drobin, Kimi, et al.
(författare)
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Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
- 2019
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 25:2, s. 306-316
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.
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| 9. |
- Holmer, Mattias, et al.
(författare)
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Determining Heart Activity Present in the Pressure Sensors of a Dialysis Machine
- 2013
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Ingår i: Computing in Cardiology. - 2325-8861. ; , s. 217-220
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Konferensbidrag (refereegranskat)abstract
- Determination of heart status during dialysis can im- prove patient monitoring. Pressure sensors in the dialysis machine measures the heart pulses that propagates in the body and enter the extracorporeal blood circuit. A peri- staltic blood pump, located in the same circuit, introduces strong periodic pressure pulses that interfere with the much weaker cardiac component. These signal characteristics make the extraction of the heart activity challenging. In the present study, we explore the possibility to extract and analyze the cardiac component using simulated data. The accuracy of the timing of each heartbeat is analyzed. Ad- ditionally, the heart component is extracted from patient pressure recordings, and compared to the heart rate com- puted from a photoplethysmogram. The results show that heart timings can be accurately determined using the pres- sure sensors of a dialysis machine.
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| 10. |
- Holmer, Mattias, et al.
(författare)
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Extracting a Cardiac Signal From the Extracorporeal Pressure Sensors of a Hemodialysis Machine
- 2015
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 62:5, s. 1305-1315
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Tidskriftsartikel (refereegranskat)abstract
- Although patients undergoing hemodialysis treatment often suffer from cardiovascular disease, monitoring of cardiac rhythm is not performed on a routine basis. Without requiring any extra sensor, this study proposes a method for extracting a cardiac signal from the built-in extracorporeal venous pressure sensor of the hemodialysis machine. The extraction is challenged by the fact that the cardiac component is much weaker than the pressure component caused by the peristaltic blood pump. To further complicate the extraction problem, the cardiac component is difficult to separate when the pump and heart rates coincide. The proposed method estimates a cardiac signal by subtracting an iteratively refined blood pump model signal from the signal measured at the extracorporeal venous pressure sensor. The method was developed based on simulated pressure signals, and evaluated on clinical pressure signals acquired during hemodialysis treatment. The heart rate estimated from the clinical pressure signal was compared to that derived from a photoplethysmographic reference signal, resulting in a difference of 0.07 +/- 0.84 beats/min. The accuracy of the heartbeat occurrence times was studied for different strengths of the cardiac component, using both clinical and simulated signals. The results suggest that the accuracy is sufficient for analysis of heart rate and certain arrhythmias.
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| 11. |
- Holmer, Mattias, et al.
(författare)
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Heart Rate Estimation from Dual Pressure Sensors of a Dialysis Machine
- 2015
-
Ingår i: 2015 Computing in Cardiology Conference (CinC). - 2325-8861. ; 42, s. 29-32
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Konferensbidrag (refereegranskat)abstract
- Dialysis patients often suffer from cardiovascular dis- eases, motivating the use of continuous monitoring of car- diac activity in clinical routine. Cardiac pressure pulses propagate through the vascular system and enter the ex- tracorporeal blood circuit of a dialysis machine, where the pulses are captured by pressure sensors. The cardiac pulses are obscured by the much stronger pressure pulses originating from the peristaltic blood pump. We have pre- viously shown that a cardiac signal can be extracted from the venous pressure signal. However, that method has been found to perform less well at very low cardiac pressure pulse amplitudes. In the present study, we propose a novel method which addresses this issue by using the signals from both the arterial and the venous pressure sensors. The method is compared to the previous method on clini- cal data using a photoplethysmogram as reference. The re- sults suggests that heart rate can be estimated more accu- rately from pressure signals with lower cardiac signal am- plitude when both arterial and venous pressure are used, compared to when only the venous signal is used.
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| 12. |
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| 13. |
- Luttens, Andreas, et al.
(författare)
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Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses
- 2022
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:7, s. 2905-2920
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Tidskriftsartikel (refereegranskat)abstract
- Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site. One hundred top-ranked compounds were tested in binding and enzymatic assays. Second, a fragment discovered by crystallographic screening was optimized guided by docking of millions of elaborated molecules and experimental testing of 93 compounds. Three inhibitors were identified in the first library screen, and five of the selected fragment elaborations showed inhibitory effects. Crystal structures of target-inhibitor complexes confirmed docking predictions and guided hit-to-lead optimization, resulting in a noncovalent main protease inhibitor with nanomolar affinity, a promising in vitro pharmacokinetic profile, and broad-spectrum antiviral effect in infected cells.
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| 14. |
- Orhan, F., et al.
(författare)
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Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
- 2016
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 84:5, s. 262-271
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Tidskriftsartikel (refereegranskat)abstract
- Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.
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| 15. |
- Raatiniemi, Lasse, et al.
(författare)
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Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis
- 2020
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 64:8, s. 1038-1047
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Forskningsöversikt (refereegranskat)abstract
- Background Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. Methods A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. Results Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. Conclusions Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.
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| 16. |
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| 17. |
- Sandberg, Frida, et al.
(författare)
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Estimation of Respiratory Information from the Built-In Pressure Sensors of a Dialysis Machine
- 2014
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Ingår i: [Host publication title missing]. - 0276-6574. ; 41, s. 853-856
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Konferensbidrag (refereegranskat)abstract
- The purpose of the present study is to determine the feasibility of estimating respiratory information from the built-in pressure sensors of a dialysis machine. The study database consists of simultaneous recordings of pressure signals and capnographic signals from 6 patients during 7 hemodialysis treatment sessions. Respiration rates were estimated using respiratory induced variations in the beat- to-beat interval series of the cardiac component of the pressure signal and respiratory induced baseline varia- tions in the pressure signal, respectively. The estimated respiration rates were compared to a reference respira- tion rate determined from the capnograhpic signal. The root-mean-square error of the estimated respiration rate from the baseline variations of the pressure signal was 2.10 breaths/min; the corresponding error of the estimated res- piration rate from the beat-to-beat interval series of the cardiac component was 4.95 breaths/min. The results sug- gest that it is possible to estimate respiratory information from the pressure sensors.
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| 18. |
- Sandberg, Frida, et al.
(författare)
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Prediction of hypotension in hemodialysis patients
- 2014
-
Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 35:9, s. 1885-1898
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Tidskriftsartikel (refereegranskat)abstract
- Intradialytic hypotension (IDH) is the most common adverse complication during hemodialysis. Its early prediction and prevention will dramatically improve the quality of life for patients with an end stage renal disease. In a recent study, changes in the normalized envelope of the test statistic of the photoplethysmograpic (PPG) signal were found to predict acute symptomatic IDH. In the present study, the PPG-based predictor is generalized to include a patient-dependent threshold which incorporates on-line information on heart rate variability and heart rate turbulence. From datasets with patients prone and resistant to IDH, the results show that symptomatic IDH could be correctly predicted in 9 out of 14 cases, while 5 out of 24 were falsely predicted. In a subset of the data containing only patients prone to IDH, acute symptomatic IDH could be correctly predicted in 5 out of 5 cases, with one false prediction out of 14. When testing the robustness of the predictor, no significant changes were observed in the test statistic when controlled changes occurred in dialysis fluid temperature, ultrafiltration rate and body position.
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| 19. |
- Sandberg, Frida, et al.
(författare)
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Prediction of intradialytic hypotension using PPG and ECG
- 2013
-
Ingår i: 2013 Computing in Cardiology. - 9781479908844 ; 40, s. 1227-1230
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Konferensbidrag (refereegranskat)abstract
- Intradialytic hypotension (IDH) is the most common complication during hemodialysis; early prediction and prevention of IDH would dramatically improve the living conditions for patients with end stage renal disease. A recently published study suggests that a decrease in the envelope of the photoplethysmograpy (PPG) signal can be used for predicting acute symptomatic IDH. In the present study, the PPG based method is extended by introducing a patient dependent detection threshold, which involves information on heart rate variability (HRV) and heart rate turbulence (HRT) from the current dialysis session. This is motivated since several studies have found significant differences in HRV and HRT between hypotension-prone and hypotension-resistant patients. Recordings from 15 patients during 38 hemodialysis sessions were used to evaluate the method. Symptomatic IDH was correctly predicted in 9 out of 14 cases, while 5 out of 24 cases were falsely predicted. The performance was better for acute symptomatic IDH, 5 out of 5 cases were correctly predicted. The present method represents a novel approach to combining information derived from ECG and PPG signals.
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| 20. |
- Shalaly, Nancy Dekki, et al.
(författare)
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Positive Modulation of the Glycine Receptor by Means of Glycine Receptor-Binding Aptamers
- 2015
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Ingår i: Journal of Biomolecular Screening. - : Sage Publications. - 1087-0571 .- 1552-454X. ; 20:9, s. 1112-1123
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Tidskriftsartikel (refereegranskat)abstract
- According to the gate control theory of pain, the glycine receptors (GlyRs) are putative targets for development of therapeutic analgesics. A possible approach for novel analgesics is to develop a positive modulator of the glycine-activated Cl- channels. Unfortunately, there has been limited success in developing drug-like small molecules to study the impact of agonists or positive modulators on GlyRs. Eight RNA aptamers with low nanomolar affinity to GlyR1 were generated, and their pharmacological properties analyzed. Cytochemistry using fluorescein-labeled aptamers demonstrated GlyR1-dependent binding to the plasma membrane but also intracellular binding. Using a fluorescent membrane potential assay, we could identify five aptamers to be positive modulators. The positive modulation of one of the aptamers was confirmed by patch-clamp electrophysiology on L(tk) cells expressing GlyR1 and/or GlyR1. This aptamer potentiated whole-cell Cl- currents in the presence of low concentrations of glycine. To our knowledge, this is the first demonstration ever of RNA aptamers acting as positive modulators for an ion channel. We believe that these aptamers are unique and valuable tools for further studies of GlyR biology and possibly also as tools for assay development in identifying small-molecule agonists and positive modulators.
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| 21. |
- Sörnmo, Leif, et al.
(författare)
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Noninvasive techniques for prevention of intradialytic hypotension
- 2012
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 5, s. 45-59
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Tidskriftsartikel (refereegranskat)abstract
- Episodes of hypotension during hemodialysis treatment constitutes an important clinical problem which has received considerable attention in recent years. Despite the fact that numerous approaches to reducing the frequency of intradialytic hypotension (IDH) have been proposed and evaluated, the problem has not yet found a definitive solution--an observation which, in particular, applies to episodes of acute, symptomatic hypotension. This overview covers recent advances in methodology for predicting and preventing IDH. Following a brief overview of well-established hypotension-related variables, including blood pressure, blood temperature, relative blood volume, and bioimpedance, special attention is given to electrocardiographic and photoplethysmographic (PPG) variables and their significance for IDH prediction. It is concluded that cardiovascular variables which reflect heart rate variability, heart rate turbulence, and baroreflex sensitivity are important to explore in feedback control hemodialysis systems so as to improve their performance. The analysis of hemodialysis-related changes in PPG pulse wave properties hold considerable promise for improving prediction.
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| 22. |
- Törnblom, Oskar, et al.
(författare)
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Increasingly complex organizational design as an explicit and implicit driver for leadership development
-
Tidskriftsartikel (refereegranskat)abstract
- More organizations need to adapt to increasingly complex contexts and this often calls for more collective forms of leadership. The purpose of this study was to explore and analyze the relationship between increasingly complex organizational design and collective leadership development and individual leader development. The study used a comparative case study design and data were collected with multiple qualitative methods in two technology-, knowledge-, and project-intensive organizations. The results demonstrate that increasingly complex organizational design fosters (1) collective leadership development, (2) new opportunities for leader development, and (3) operational improvements. The study contributes to organizational design and leadership development studies and their intersection. The results illustrate the value for both researchers and practitioners in viewing collective leadership development and leader development from an organizational design perspective. Finally, the results may support practitioners in enabling leadership development in connection with the implementation of new organizational design.
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| 23. |
- Törnblom, Oskar, 1970-
(författare)
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Organizational Design and Leadership Development: The Role of Increasing Complexity
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many organizations need to adapt to increasingly complex environments. New forms of organizational design and leadership are called for and, under some circumstances, more collective leadership practices are needed. Furthermore, values and beliefs in some societal contexts foster a general positive bias for collective leadership. Paradoxically, many investment decisions regarding leadership development activities do not pay off. At the same time, the research fields of collective leadership development and on-the-job leader development are underutilized. The research field of leadership is in need of consolidation and integration within and between research areas. There has been much less research done on collective leadership development compared with leader development, and research on leadership development has been focused more on individual and collective change rather than on contextual facilitating factors such as organizational design.To address these theoretical and practical challenges, the aim of the thesis was to explore organizational design and leadership development in terms of increasing complexity in the empirical context of technology-, knowledge-, and project-intensive organizations. The research design was centered around two studies that were part of a larger interactive research project and two conceptual studies that jointly investigated (1) organizational design and increasing complexity, (2) leadership development and increasing complexity, (3) how increasingly complex organizational design can foster leadership development. The interactive research project had four goals in terms of creating common learning for the project partners involved, new academic knowledge, and organizational development not only for the participating organizations but also for organizations in general.The thesis contributes to the research fields of organizational design and leadership development as well as their intersection. It adds to theory by providing a more fine-grained definition of ways of understanding leadership development according to increasing complexity. Furthermore, it adds to the understanding of how increasingly complex organizational design can foster leadership development, especially collective leadership, thus demonstrating empirical examples of leadership development without traditional leadership development investments.The thesis proposes future research on emerging technology as an accelerator for leadership development and interactive research in partnership with organizations in order to further integrate the research fields of organizational design and leadership development. In terms of managerial contributions, a number of suggestions are offered to support better knowledge creation and decision-making regarding organizational design, on-the-job leader development, and especially collective leadership development. Furthermore, a shift from a psychology-centered leadership development approach toward more of a systemic and organizational design-centered leadership development approach that includes both individual and collective dimensions is called for. This shift will potentially change the leadership development industry, making many of the contemporary investments in leadership development obsolete.
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