Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Presence of the partner in the operating room during a category 1 cesarean section: a prospective explorative study.

BACKGROUND: Little information exists regarding attitudes related to the presence of the partner in the operation room (OR) during category 1 emergency cesarean section (cat. 1 CS). We investigated how cat. 1 CS under general anesthesia is experienced, both by partners present in the OR and those not. METHODS: An explorative prospective cohort trial, with qualitative elements, involving all cat. 1 CS in 2022 in two hospitals. At site 1 the partner was present in the OR during cat. 1 CS, whereas at site 2 the partner was not. Parents and staff answered questionnaires following each cat. 1 CS and semi-structured interviews with partners were held three months after surgery. Qualitative data were analyzed using content analysis. The primary outcome was the partner's answer to the question: "Would you have preferred not being present/being present in the OR?" respectively. RESULTS: Seventeen and eight cat. 1 CS occurred at each site respectively. All parents agreed to participate. No partners in site 1 would have preferred to wait outside, and all evaluated the experience very positively. Partners at site 2 also evaluated not being present positively. Overarching themes from the qualitative analysis were "Being the family witness" and "Experience of being the partner". Mothers and staff from site 1 were very positive about their partners' presence. CONCLUSION: Partners present in the OR during cat. 1 CS under general anesthesia evaluated this very positively. Most partners, who had not been present in the OR, also evaluated this positively. No partners had post-traumatic stress.

Inflammatory response in patients undergoing uterine artery embolization as compared to patients undergoing conventional hysterectomy.

BACKGROUND: Uterine fibroids are benign tumors seen in 20-40% of women of childbearing age, and these fibroids are usually treated by hysterectomy. During the last decade, embolization of the uterine arteries with polyvinyl alcohol microparticles has become an alternative treatment. PURPOSE: To investigate whether uterine artery embolization generates a reduced inflammatory response as compared with conventional hysterectomy. MATERIAL AND METHODS: 40 women, 20 in each group, entered this prospective, non-randomized study. The two groups were comparable concerning age, comorbidity, and body-mass index (BMI). RESULTS: We found a significant difference between the inflammatory responses in women undergoing embolization compared with the inflammatory response in women having an abdominal hysterectomy. Women undergoing embolization were subjected to a much smaller inflammatory burden, their total morphine consumption was lower, and their return to work was faster than women subjected to conventional hysterectomy. CONCLUSION: Uterine artery embolization generates a reduced inflammatory response compared with conventional hysterectomy.

The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia.

BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity. We investigated the effect of high-volume CVVH for 24 h on the cell-mediated immunity following endotoxin infusion. METHODS: Thirty pigs were divided into three groups. Ten pigs received 30 microg/kg of Escherichia coli endotoxin. These pigs were treated with CVVH (replacement 35 ml/kg/h) over the following 24 h. Ten pigs received the same bolus of endotoxin and ten pigs served as a control group. The adhesion molecules CD18, CD44 and CD62L and the ability to respond with an oxidative burst were measured. The number of neutrophils was counted in blood and lung tissue. The lymphoproliferative response and cytokines interleukin-6 and interleukin-10 were measured. RESULTS: The infusion of endotoxin was followed by initial granulocytopenia and, later, granulocytosis, activation of CD18 and CD62L, and increased oxidative burst. The cytokine level was increased. CVVH had no effect on the adhesion molecules or cytokine level and did not reduce the number of granulocytes in the lung significantly. CVVH, however, reduced the oxidative burst activity of neutrophils after 2 h of treatment. CONCLUSION: In the first few hours after endotoxaemia, high-volume CVVH reduced the oxidative burst activity of neutrophils. However, in the long term, CVVH was unable to modify the endotoxin-induced changes in cell-mediated immunity.