A study protocol for the cardiac effects of a single dose of either oxytocin 2.5 IU or carbetocin 100 µg after caesarean delivery: a prospective randomized controlled multi-centre trial in Norway.

Background: Both oxytocin and carbetocin are used to prevent uterine atony and post-partum haemorrhage after caesarean delivery in many countries, including Norway. Oxytocin causes dose-dependent ST-depression, troponin release, prolongation of QT-time and arrythmia, but little is known about myocardial effects of carbetocin. We have previously demonstrated comparable vasodilatory effects of oxytocin and carbetocin and are now undertaking a Phase 4 trial to investigate whether carbetocin causes similar changes to myocardial markers compared with oxytocin. Methods: Our randomized controlled trial will be conducted at three obstetrics units at Oslo University Hospital and Akershus University Hospital, Norway. Planned enrolment will be of 240 healthy, singleton pregnant women aged 18 to 50 years undergoing planned caesarean delivery. Based on pilot study data, each participant will receive a one-minute intravenous injection of either oxytocin 2.5 IU or carbetocin 100 µg during caesarean delivery. The prespecified primary outcome is the change from baseline in high-sensitive troponin I plasma concentrations at 6-10 hours after study drug administration. Secondary outcomes include uterine tone grade at 2.5 and five minutes after study drug administration, adverse events for up to 48 hours after study drug administration, estimated blood loss within eight hours of delivery, need for rescue treatment and direct/indirect costs. Enrolment and primary analysis are expected to be completed by the end of 2021. Discussion: Women undergoing caesarean delivery should be assessed for cardiovascular risk particularly as women with an obstetric history of pregnancy induced hypertension, gestational diabetes mellitus, preterm birth, placental abruption, and stillbirth are at increased risk of future cardiovascular disease. Any additional ischaemic myocardial risk from uterotonic agents will need to be balanced with the benefit of reducing the risk of postpartum haemorrhage. Any potential cardiotoxicity difference between oxytocin and carbetocin will help inform treatment decisions for pregnant women. Registration: Clinicaltrials.gov NCT03899961 (02/04/2019).

Long-term outcome after pregnancy-related venous thrombosis.

There is limited knowledge of the long-term outcomes after pregnancy-related venous thrombosis (VT). Cohort studies monitoring long-term complications have never been conducted in this population, and the present evidence is based on data from a few observational studies. The risk of post-thrombotic syndrome (PTS) as a long-term complication after deep vein thrombosis (DVT) in pregnancy is considerable. It is most pronounced in women with a proximal DVT occurring postpartum. Quality of life (QOL) is reduced, but limited to women who develop PTS. Mortality is higher than in the general population during the first year after acute thrombosis, but not thereafter, and the long-term risk of cancer does not seem to be increased. The long-term risk of recurrent VT, subsequent arterial thrombosis, or chronic thromboembolic pulmonary hypertension is unknown and more research is highly warranted.

Adaptation of trustworthy guidelines developed using the GRADE methodology: a novel five-step process.

BACKGROUND: Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting. METHODS: Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process. RESULTS: We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future. CONCLUSIONS: This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

Applying new strategies for the national adaptation, updating, and dissemination of trustworthy guidelines: results from the Norwegian adaptation of the Antithrombotic Therapy and the Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. We describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination. METHODS: A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updated the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using the web-based Making GRADE the Irresistible Choice Guideline Authoring and Publication Platform. RESULTS: We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9 and condensed and restructured them into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best-practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates, and reevaluation of the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013. CONCLUSIONS: New strategies for adapting, updating, and disseminating trustworthy guidelines proved feasible and will provide Norwegian health-care professionals and patients with up-to-date guidance tailored to national circumstances.