Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark: A nationwide observational study.

BACKGROUND: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status. METHODS: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant. RESULTS: Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10-19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%. CONCLUSIONS: In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.

Psychological wellbeing of Australian community health service staff during the COVID-19 pandemic: a longitudinal cohort study.

BACKGROUND: Hospital clinical staff have reported poor psychosocial wellbeing during the COVID-19 pandemic. Little is known about community health service staff who undertake various roles including education, advocacy and clinical services, and work with a range of clients. Few studies have collected longitudinal data. The aim of this study was to assess the psychological wellbeing of community health service staff in Australia during the COVID-19 pandemic at two time points in 2021. METHODS: A prospective cohort design with an anonymous cross-sectional online survey administered at two time points (March/April 2021; n = 681 and September/October 2021; n = 479). Staff (clinical and non-clinical roles) were recruited from eight community health services in Victoria, Australia. Psychological wellbeing was assessed using the Depression, Anxiety and Stress Scale (DASS-21) and resilience using the Brief Resilience Scale (BRS). General linear models were used to measure the effects of survey time point, professional role and geographic location on DASS-21 subscale scores, adjusting for selected sociodemographic and health characteristics. RESULTS: There were no significant differences in respondent sociodemographic characteristics between the two surveys. Staff's mental health declined as the pandemic continued. Adjusting for dependent children, professional role, general health status, geographic location, COVID-19 contact status and country of birth; depression, anxiety and stress scores were significantly higher for respondents in the second survey than the first (all p < 0.001). Professional role and geographic location were not statistically significantly associated with scores on any of the DASS-21 subscales. Higher levels of depression, anxiety and stress were reported among respondents who were younger, and had less resilience or poorer general health. CONCLUSIONS: The psychological wellbeing of community health staff was significantly worse at the time of the second survey than the first. The findings indicate that the COVID-19 pandemic has had an ongoing and cumulative negative impact on staff wellbeing. Staff would benefit from continued wellbeing support.

Attendance at, and experiences of, urban hospital outpatient appointments: informing a new model of care for urban-dwelling Aboriginal and Torres Strait Islander patients.

Objectives To compare outpatient attendance rates for Aboriginal and Torres Strait Islander ('Aboriginal') and non-Aboriginal patients at a large metropolitan health service in Melbourne, Australia, and to describe the barriers and enablers experienced by urban-dwelling Aboriginal patients in attending hospital outpatient appointments. Methods This study used a mixed-method approach. Proportions of referred patients who booked and attended outpatient appointments were extracted from a health service database. Aboriginal versus non-Aboriginal cohorts were compared using chi-squared tests. Eleven patients, one parent of a patient and two community nurses were interviewed by telephone to investigate perceived barriers and enablers to attending outpatient appointments among Aboriginal patients. Results Outpatient referrals were greater among Aboriginal than non-Aboriginal people; however, referrals were significantly less likely to result in an outpatient clinic booking and attendance for Aboriginal compared to non-Aboriginal people. Interview participants reported several barriers to attending appointments, related to logistical, quality of care and cultural factors. Suggested facilitators to make appointment attendance easier included: provision of transport support, improving clinic scheduling, utilising a variety of appointment reminder formats, providing food in waiting rooms, flexible appointment timing options, outreach services, access to Aboriginal support workers, improving communication and relationships with Aboriginal people, cultural awareness training for staff and the provision of culturally appropriate spaces. Conclusion Some barriers faced by Aboriginal patients in attending hospital outpatient appointments in urban areas can be addressed through implementation of enablers suggested by participants. Data have informed the development of a tailored, inclusive, culturally and consumer-focused appropriate hospital outpatient service model of care.

Association between days alive without life support/out of hospital and health-related quality of life.

BACKGROUND: Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health-related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with HRQoL is uncertain. We thus aimed to assess the associations between DAWOLS and DAOOH and long-term HRQoL. METHODS: Secondary analysis of the COVID STEROID 2 trial including adults with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial including adult intensive care unit patients with acute hypoxaemic respiratory failure. Associations between DAWOLS and DAOOH at day 28 and 90 and long-term HRQoL (after 6 or 12 months) using the EuroQol 5-dimension 5-level survey (EQ VAS and EQ-5D-5L index values) were assessed using flexible models and evaluated using measures of fit and prediction adequacy in both datasets (comprising internal performance and external validation), non-parametric correlation coefficients and graphical presentations. RESULTS: We found no strong associations between DAWOLS or DAOOH and HRQoL in survivors at HRQoL-follow-up (615 and 1476 patients, respectively). There was substantial variability in outcomes, and predictions from the best fitted models were poor both internally and externally in the other trial dataset, which also showed inadequate calibration. Moderate associations were found when including non-survivors, although predictions remained uncertain and calibration inadequate. CONCLUSION: DAWOLS and DAOOH were poorly associated with HRQoL in adult survivors of severe or critical illness included in the COVID STEROID 2 and HOT-ICU trials.

Lower or higher oxygenation targets for acute Hypoxaemic respiratory failure: Protocol for an individual patient data meta-analysis.

BACKGROUND: Supplemental oxygen therapy is central to the treatment of acute hypoxaemic respiratory failure, a condition which remains a major driver for morbidity and mortality in intensive care. Despite several large randomised clinical trials comparing a higher versus a lower oxygenation target for these patients, significant differences in study design impede analysis of aggregate data and final clinical recommendations. METHODS: This paper presents the protocol for conducting an individual patient data meta-analysis where full individual patient data according to the intention-to-treat principle will be pooled from the HOT-ICU and HOT-COVID trials in a one-step procedure. The two trials are near-identical in design. We plan to use a hierarchical general linear mixed model that accounts for data clustering at a trial and site level. The primary outcome will be 90-day all-cause mortality while the secondary outcome will be days alive without life-support at 90 days. Further, we outline 14 clinically relevant predefined subgroups which we will analyse for heterogeneity in the intervention effects and interactions, and we present a plan for assessing the credibility of the subgroup analyses. CONCLUSION: The presented individual patient data meta-analysis will synthesise individual level patient data from two of the largest randomised clinical trials on targeted oxygen therapy in intensive care. The results will provide a re-analysis of the intervention effects on the pooled intention-to-treat populations and facilitate subgroup analyses with an increased power to detect clinically important effect modifications.

Impact of the COVID-19 pandemic on Australian community health service staff's occupational and personal lives: a longitudinal study.

BACKGROUND: Little is known about the impact of the coronavirus disease 2019 (COVID-19) pandemic on community health service staff. The aim of this study was to assess the immediate and longer-term psychosocial impacts of COVID-19 on community health service staff in Australia. METHODS: A prospective cohort design with an anonymous cross-sectional online survey that was administered at two time points (March-April 2021; n=681 and September-October 2021; n=479). Staff (clinical and non-clinical) were recruited from eight community health services in Victoria, Australia. Study-specific questions evaluated the impact of COVID-19 on respondents' work and personal lives. Space was provided at the end of the surveys for free-text comments. RESULTS: There were no significant differences in respondent characteristics between the two surveys. At both survey time points, respondents were mostly concerned about their family's health. Compared to the first survey, survey two respondents were significantly more likely to report concerns about infecting family members (48.8% vs 41.6%, P=0.029), clients having COVID-19 (43.2% vs 36.2%, P=0.035), getting COVID-19 at work (53.7% vs 45.6%, P=0.014), not being prepared to care for clients with COVID-19 (27.5% vs 18.8%, P=0.006) and feeling more stress at work (63.7% vs 50.8%, P<0.001). A significantly greater proportion of respondents indicated they were considering transitioning into another sector at the time of the second survey compared to the first (24.8% vs 18.7%, P=0.026). CONCLUSIONS: The COVID-19 pandemic has had a considerable impact on the work and personal lives of community health service staff. Staff would benefit from continued and targeted initiatives that address their wellbeing and concerns.

Thromboembolic and bleeding events in ICU patients with COVID-19: A nationwide, observational study.

BACKGROUND: Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic. METHODS: This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90-day mortality were estimated using Cox regression analyses. RESULTS: We included 1369 patients in this sub-study; 158 (12%, 95% confidence interval 10-13) had a thromboembolic event in ICU and 309 (23%, 20-25) had a bleeding event, among whom 81 patients (6%, 4.8-7.3) had major bleeding. We found that mechanical ventilation and increased D-dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91-2.01, p = .14], whereas bleeding events were 1.55 [1.18-2.05, p = .002]). CONCLUSIONS: Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID-19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.

Worsening general health and psychosocial wellbeing of Australian hospital allied health practitioners during the COVID-19 pandemic.

ObjectiveTo describe self-reported general and psychological health for allied health practitioners at an Australian acute public health service over three time points within the coronavirus disease 2019 (COVID-19) pandemic.MethodsThis study collected data from cross-sectional online surveys at three time points: May-June 2020 (T1), October-November 2020 (T2) and November-December 2021 (T3). The self-report questionnaire consisted of demographic questions, a general health question and the 21-item version of the Depression Anxiety Stress Scales (DASS-21).ResultsA total of 308 responses were received (T1 n = 135, T2 n = 78, T3 n = 95) from representatives of eight allied health professions. The proportion of allied health practitioners reporting poor general health significantly increased over time, as did mean scores on all DASS-21 sub-scales. General health status was also significantly associated with DASS-21 subscale scores. Anxiety scores increased significantly between T1 and T2, while depression scores increased significantly between T2 and T3. Significant increases in stress scores were recorded across all time intervals. Between T1 and T3, the proportion of allied health practitioners reporting moderate, severe, or extremely severe symptoms increased for depression (10.3-30.9%), anxiety (5.2-18.2%) and stress (13.3-36.3%).ConclusionThe general and psychological health of allied health practitioners appears to be worsening as the COVID-19 pandemic continues. Organisational strategies to support the health of the allied health workforce in acute care settings must address the cumulative effects of prolonged pressure on their general and psychosocial health. Support strategies need to be responsive to changes in psychological wellbeing at different phases of the pandemic.

Beyond the case numbers: Social determinants and contextual factors in patient narratives of recovery from COVID-19.

OBJECTIVE: This study aimed to describe and contextualise COVID-19 recovery from the perspective of patient-lived experience, to inform the evolving public health response to the pandemic. METHODS: Narrative interviews were completed with 37 adult Australians between six and 10 months following their COVID-19 diagnosis. Verbatim transcripts were analysed thematically and trustworthiness was supported by multiple strategies to ensure rigour. RESULTS: Three themes were identified: 1) trajectories of recovery, 2) back to 'some sort of normal' and 3) the importance of work. Resumed participation in activities of daily life, the influence of social determinants of health and the impact of contextual factors were prominent features in the recovery narratives. CONCLUSIONS: The COVID-19 pandemic presents both challenges and opportunities for public health systems to formulate appropriate responses and make improvements. Behind the case numbers, patient narratives described the uncertainty, diversity and multiple pathways to recovery that need to inform public health policy. IMPLICATIONS FOR PUBLIC HEALTH: Looking beyond the case numbers reveals a complex landscape characterised by uncertainty, diversity and multiple pathways to recovery. The pandemic presents challenges and opportunities for public health in Australia and New Zealand, lived experience expertise is crucial to the formulation of an effective response.

Nurse, midwife and patient perspectives and experiences of diabetes management in an acute inpatient setting: a mixed-methods study.

BACKGROUND: In an acute hospital setting, diabetes can require intensive management with medication modification, monitoring and education. Yet little is known about the experiences and perspectives of nursing/midwifery staff and patients. The aim of this study was to investigate diabetes management and care for patients with diabetes in an acute care setting from the perspectives of nursing/midwifery staff and patients. METHODS: A convergent mixed-methods study design. Patients with diabetes (Type 1, Type 2 or gestational diabetes) recruited from a public health service in Melbourne, Australia completed a survey and nurses and midwives employed at the health service participated in focus groups. Descriptive statistics were used to summarise the survey data. Thematic analysis was used for the free-text survey comments and focus group data. RESULTS: Surveys were completed by 151 patients. Although more than half of the patients were satisfied with the diabetes care they had received (n = 96, 67.6%), about a third felt the hospital nursing/midwifery staff had ignored their own knowledge of their diabetes care and management (n = 43, 30.8%). Few reported having discussed their diabetes management with the nursing/midwifery staff whilst in hospital (n = 47, 32.6%) or thought the nurses and midwives had a good understanding of different types of insulin (n = 43, 30.1%) and their administration (n = 47, 33.3%). Patients also reported food related barriers to their diabetes management including difficulties accessing appropriate snacks and drinks (n = 46, 30.5%), restricted food choices and timing of meals (n = 41, 27.2%). Fourteen nurses and midwives participated in two focus groups. Two main themes were identified across both groups: 1. challenges caring for patients with diabetes; and 2. lack of confidence and knowledge about diabetes management. CONCLUSIONS: Patients and nursing/midwifery staff reported challenges managing patients' diabetes in the hospital setting, ensuring patients' optimal self-management, and provision of suitable food and timing of meals. It is essential to involve patients in their diabetes care and provide regular and up-to-date training and resources for nursing/midwifery staff to ensure safe and high-quality inpatient diabetes care and improve patient and staff satisfaction.

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark.

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID-19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID-19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalised patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.

Long-term cognitive and functional status in Danish ICU patients with COVID-19.

BACKGROUND: ICU admission due to COVID-19 may result in cognitive and physical impairment. We investigated the long-term cognitive and physical status of Danish ICU patients with COVID-19. METHODS: We included all patients with COVID-19 admitted to Danish ICUs between March 10 and May 19, 2020. Patients were the contacted prospectively at 6 and 12 months for follow-up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6- and 12-month mortality, health-related quality of life (HRQoL) assessed by EQ-5D-5L, functional status (Barthel activities of daily living and Lawton-Brody instrumental activities of daily living), and fatigue (Fatigue Assessment Scale). The study had no information on pre-ICU admission status for the participants. RESULTS: A total of 326 patients were included. The 6- and 12-month mortality was 37% and 38%, respectively. Among the 204 six-month survivors, 105 (51%) participated in the 6-month follow-up; among the 202 twelve-month survivors, 95 (47%) participated in the 12-month follow-up. At 6 months, cognitive scores indicated impairment for 26% (95% confidence interval [CI], 11.4-12.4) and at 12 months for 17% (95% CI, 12.0-12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4-3.9) at 6 months, and for 18% (95% CI, 3.3-3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months. CONCLUSION: Long-term cognitive, functional impairment was found in up to one in four of patients surviving intensive care for COVID-19. Fatigue was present in nearly half the survivors at both 6 and 12 months. However, pre-ICU admission status of the patients was unknown.

Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial.

BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO2 /FiO2 ratio in patients with COVID-19 and severe respiratory insufficiency. METHODS: Investigator-initiated, randomized, open-label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID-19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO2 /FiO2 ratio at 72 h. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non-invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7-71.2). The primary outcome, PaO2 /FiO2 ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference -5.1 kPa [95% CI -10.2, -0.04] p = .05). The 28-day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06-2.07, p = .26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO2 /FiO2 ratio at 72 h with no differences for other outcomes.

Hospital clinicians' psychosocial well-being during the COVID-19 pandemic: longitudinal study.

BACKGROUND: Hospital clinicians report poor psychosocial well-being during the COVID-19 pandemic. Few studies have reported data at more than one time point. AIMS: To compare psychosocial well-being among hospital clinicians at two different time points during the COVID-19 pandemic in 2020. METHODS: Participants included doctors, nurses, midwives and allied health clinicians at a multi-site, public health service in Melbourne, Australia. Data were collected via two cross-sectional, online surveys: May to June (wave 1; n = 638) and October to December 2020 (wave 2; n = 358). The Depression, Anxiety and Stress Scale (DASS-21) assessed psychological well-being in the past week. Investigator-devised questions assessed COVID-19 concerns and perceived work impacts. General linear models were used to assess impact of wave on psychological distress. RESULTS: There were no significant demographic differences between the two groups. Both positive (e.g. learning experience) and negative (e.g. risk of getting COVID-19) impacts were reported. In both waves, staff were most concerned about health risks to family members. Wave 2 respondents were significantly more likely than wave 1 respondents to indicate concerns about colleagues having COVID-19, increased workloads, leave cancellation and increased conflict at work (all P < 0.001). Adjusting for sex, age, self-rated health and discipline group, depression, anxiety and stress scores were significantly higher for respondents in the second than the first wave (all P < 0.001). CONCLUSIONS: Psychological well-being of hospital clinicians was significantly worse during the second wave of the COVID-19 pandemic than the first. Sustained occupational and psychosocial support is recommended even when immediate COVID-19 concerns and impacts resolve.

Patient preferences using telehealth during the COVID-19 pandemic in four Victorian tertiary hospital services.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has had a major impact on healthcare services with many changes to telehealth care delivery. More information is needed about the patient perspective of telehealth in hospital services and the potential costs and benefits for patients. AIM: To measure patients' evaluation of telehealth, preferences for telehealth versus in-person appointments, and potential cost savings by patient characteristics. METHODS: A cross-sectional online survey (including patient and appointment characteristics, telehealth evaluation, preferences for care and costs) of adult patients using video telehealth in four metropolitan tertiary hospital services in Melbourne, Victoria. RESULTS: A total of 1045 patients (median age 44 years; interquartile range 29-59) participated with an overall response rate of 9.2%. For 98.7% patients, telehealth was convenient, 96.4% stated that it saved time, 95.9% found telehealth acceptable to receive care and 97.0% found that telehealth improved their access to care. Most (62.6%) preferred in-person consultations, although 86.9% agreed that telehealth was equivalent to an in-person consultation. Those in regional and rural areas were less likely to prefer in-person consultations. Patients attending for medical reasons were less likely to prefer in-person consultation compared with patients with surgical reasons. Patient preference to telehealth was independent of level of education, appointment type, self-rated health status and socio economic status. Patients saved an average of A$120.9 (standard deviation A$93.0) per appointment, with greater cost savings for patients from low and middle socio economic areas and regional or rural areas. CONCLUSION: Telehealth video consultations were largely evaluated positively with most patients considering the service to be as good as in-person. Understanding patient preference is critical to consider when implementing telehealth as mainstream across hospital health services.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

Guided self-determination intervention versus attention control for people with type 2 diabetes in outpatient clinics: a protocol for a randomised clinical trial.

INTRODUCTION: In the management of type 2 diabetes, autonomy-supporting interventions may be a prerequisite to achieving more long-term improvement. Preliminary evidence has shown that the guided self-determination (GSD) method might have an effect on haemoglobin A1c and diabetes distress in people with type 1 diabetes. Previous trials were at risk of uncertainty. Thus, the objective is to investigate the benefits and harms of a GSD intervention versus an attention control group intervention in adults with type 2 diabetes. METHODS AND ANALYSIS: This trial protocol is guided by the The Standard Protocol Items: Recommendations for International Trials Statement. We describe the protocol for a pragmatic randomised, dual-centre, parallel-group, superiority clinical trial testing a GSD intervention versus an attention control for people with type 2 diabetes in outpatient clinics. The participants (n=224) will be recruited from two diverse regions of Denmark. The experimental stepped-care intervention will consist of three to five GSD sessions lasting up to 1 hour with a trained GSD facilitator. The sessions will be conducted face to face, by video conference or over the telephone. The attention controls will receive three to five sessions lasting up to an hour with a communication-trained healthcare professional provided face to-face, by video conference, or over the telephone. Participants will be included if they have type 2 diabetes,>18 years old, are not pregnant. Participants will be assessed before randomisation, at 5-month, and 12-month follow-up, the latter being the primary. The primary outcome is diabetes distress. Secondary outcomes are quality of life, depressive symptoms and non-serious adverse events. Exploratory outcomes are haemoglobin A1c, motivation and serious adverse events. Data will be collected using REDCap and analysed using Stata V.16. ETHICS AND DISSEMINATION: The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its latest form, International Harmonisation of Good Clinical Practice guidelines and the applicable regulatory requirement(s). The trial has been approved by the Danish Data Protection Agency (P-2020-864). The Ethics Committee of the Capital Region of Denmark reviewed the trial protocol, but exempted the trial protocol from full review (H-20003638). The results of the trial will be presented at the outpatient clinics treating people with type 2 diabetes, at national and international conferences as well as to associations for people with diabetes and their relatives. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04601311.

Higher versus lower oxygenation targets in COVID-19 patients with severe hypoxaemia (HOT-COVID) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Respiratory failure is the main cause of mortality and morbidity among ICU patients with coronavirus disease 2019 (COVID-19). In these patients, supplemental oxygen therapy is essential, but there is limited evidence the optimal target. To address this, the ongoing handling oxygenation targets in COVID-19 (HOT-COVID) trial was initiated to investigate the effect of a lower oxygenation target (partial pressure of arterial oxygen (PaO2 ) of 8 kPa) versus a higher oxygenation target (PaO2 of 12 kPa) in the ICU on clinical outcome in patients with COVID-19 and hypoxaemia. METHODS: The HOT-COVID is planned to enrol 780 patients. This paper presents the protocol and statistical analysis plan for the conduct of a secondary Bayesian analysis of the primary outcome of HOT-COVID being days alive without life-support at 90 days and the secondary outcome 90-day all-cause mortality. Furthermore, both outcomes will be investigated for the presence heterogeneity of treatment effects based on four baseline parameters being sequential organ failure assessment score, PaO2 /fraction of inspired oxygen ratio, highest dose of norepinephrine during the 24 h before randomisation, and plasma concentration of lactate at randomisation. CONCLUSION: The results of this pre-planned secondary Bayesian analysis will complement the primary frequentist analysis of the HOT-COVID trial and may facilitate a more nuanced interpretation of the trial results.