Ethics approval and consent to participate
Participants in both RCTs received written and oral information, and they or their next of kin was consulted to provide written informed consent on their behalf. Participants and/or next of kin were informed that they could withdraw at any time with no repercussion. The RCTs were approved by the Regional Ethical Review Board in Umeå, Sweden (Dnr 00–137 and Dnr 08-053 M), and amendments for this study was approved by the Swedish Ethical Review Authority (Dnr 2021–00024 and Dnr 2021–00681). All methods were performed in accordance to the Declaration of Helsinki.