Effects of a lower versus a higher oxygenation target in intensive care unit patients with chronic obstructive pulmonary disease and acute hypoxaemic respiratory failure: a subgroup analysis of a randomised clinical trial.

Background: Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established. Methods: This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [Pao2] of 8 kPa) vs a higher target (Pao2 of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD. Results: The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median Pao2 was 9.1 kPa (inter-quartile range 8.7-9.9) in the lower group vs 12.1 kPa (11.2-12.9) in the higher group. Data for arterial carbon dioxide (Paco2) were available for 497 patients (88%) with no between-group difference in time-weighted average; median Paco2 6.0 kPa (5.2-7.2) in the lower group vs 6.2 kPa (5.4-7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died vs 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82-1.17; P=0.67). No statistically significant differences were found in any secondary outcome. Conclusions: In ICU patients with COPD and acute hypoxaemia, a lower vs a higher oxygenation target did not reduce mortality. There were no between-group differences in Paco2 or in secondary outcomes. Clinical trial registration: NCT03174002, EudraCT number 2017-000632-34.

The digital divide in rural and regional communities: a survey on the use of digital health technology and implications for supporting technology use.

OBJECTIVE: A digital divide exists for people from rural and regional areas where they are less likely and confident to engage in digital health technologies. The aim of this study was to evaluate the digital health literacy and engagement of people from rural and regional communities, with a focus on identifying barriers and facilitators to using technology. RESULTS: Forty adults living in rural/regional areas completed a survey consisting of the eHealth Literacy Scale (eHEALS) with additional items surveying participants' experience with a range of digital health technologies. All participants had used at least one digital health technology. Most (80%) participants had an eHEALS score of 26 or above indicating confidence in online health information. Commonly reported barriers to digital health technology use centred on product complexity and reliability, awareness of resources, lack of trust, and cost. Effective digital health technology use is becoming increasingly important, there may be a need to prioritise and support people with lower levels of digital health literacy. We present opportunities to support community members in using and accessing digital health technology.

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery.

INTRODUCTION: Hypoxic pulmonary vasoconstriction (HPV) can be a challenging clinical problem. It is not fully elucidated where in the circulation the regulation of resistance takes place. It is often referred to as if it is in the arteries, but we hypothesized that it is in the venous side of the pulmonary circulation. METHODS: In an open thorax model, pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels. At the same time the lungs were ventilated with extreme variations of inspired air from 5% to 100% oxygen, making it possible to make combinations of high and low oxygen content through the pulmonary circulation. A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests. Under different combinations of oxygenation, pulmonary vascular resistance (PVR) was calculated. RESULTS: With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein, PVR was doubled. With more extreme hypoxia PVR suddenly decreased. Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins. DISCUSSION: The impact of hypoxia occurs from the alveolar level and forward with the blood flow. The experiments indicated that the regulation of PVR is mediated from the venous side.

Safety and Efficacy of Midline vs Peripherally Inserted Central Catheters Among Adults Receiving IV Therapy: A Randomized Clinical Trial.

Importance: Midline catheters (MCs) are widely used, but safety and efficacy compared with peripherally inserted central catheters (PICCs) has not been adequately evaluated. Objective: To compare the safety and efficacy of MCs with PICCs among adult patients with an anticipated intravenous therapy lasting from 5 to 28 days. Design, Setting, and Participants: This parallel, 2-group, open-label, randomized clinical trial (RCT) was conducted in Denmark from October 2018 to February 2022 at a single academic tertiary care center. Adult inpatients and outpatients were consecutively randomized. Intervention: Patients were randomized in a 1:1 ratio to either the MC group or the PICC control group. Main Outcomes and Measures: The primary outcome was catheter-related bloodstream infection (CRBSI), analyzed using the Fisher exact test. Secondary outcomes were symptomatic catheter-related thrombosis and catheter failure, including mechanical cause, phlebitis, infiltration, pain in relation to drug or fluid administration, and leaking from the puncture site. Incidence rate ratios (IRRs) were calculated to assess between-group failure rates over device dwell time using Poisson regression. An intention-to-treat analysis was performed. Results: A total of 304 patients (mean [SD] age, 64.6 [13.5] years; 130 [42.8%] female) were included in the analysis, and 152 patients were allocated to each catheter group. The incidence of CRBSI was low, with 0 in the MC group and 1 in the PICC control group (P > .99). The MC group had a higher catheter-related complication rate (20 [13.2%] vs 11 [7.2%]), and an IRR of 2.37 (95% CI, 1.12-5.02; P = .02) for complications compared with the PICC control group. In a post hoc analysis stratified by catheter dwell time, no significant difference in complication rate (IRR, 1.16; 95% CI, 0.50-2.68; P = .73) was found between the 2 groups for catheters used less than 16 days. Conclusions and Relevance: In this RCT with patients who received medium- to long-term intravenous therapy, the incidence of CRBSI was low, with no difference between MCs and PICCs. The use of MCs resulted in a higher incidence of catheter-related complications compared with use of PICCs. This finding should be balanced in the decision of type of catheter used at the individual patient level. Trial Registration: ClinicalTrials.gov Identifier: NCT04140916.

Long-term cognitive and pulmonary functions following a lower versus a higher oxygenation target in the HOT-ICU and HOT-COVID trials: A protocol update.

BACKGROUND: The Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial was a multicentre, randomised, parallel-group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO2 ] = 8 kPa) versus a higher oxygenation target (PaO2 = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure; the Handling Oxygenation Targets in coronavirus disease 2019 (HOT-COVID) tested the same oxygenation targets in patients with confirmed COVID-19. In this study, we aim to evaluate the long-term effects of these oxygenation targets on cognitive and pulmonary function. We hypothesise that a lower oxygenation target throughout the ICU stay may result in cognitive impairment, whereas a higher oxygenation target may result in impaired pulmonary function. METHODS: This is the updated protocol and statistical analysis plan of two pre-planned secondary outcomes, the long-term cognitive function, and long-term pulmonary function, in the HOT-ICU and HOT-COVID trials. Patients enrolled in both trials at selected Danish sites and surviving to 1 year after randomisation are eligible to participate. A Repeatable Battery for the Assessment of Neuropsychological Status score and a full-body plethysmography, including diffusion capacity for carbon monoxide, will be obtained. The last patient is expected to be included in the spring of 2024. CONCLUSION: This study will provide important information on the long-term effects of a lower versus a higher oxygenation target on long-term cognitive and pulmonary functions in adult ICU patients with acute hypoxaemic respiratory failure.

"I always felt like I wasn't supposed to be there". An international qualitative study of fathers' engagement in family healthcare during transition to fatherhood.

OBJECTIVE: Engagement of fathers in family health services confers benefits for the health and wellbeing of the whole family. The childbirth continuum is traditionally considered a feminine event, however, commensurate with the changing paradigm of gender equity in family healthcare worldwide, the role of fathers is in transformation. The aim of the study is to explore father's perceptions and experiences of healthcare engagement during pregnancy and early infant care. DESIGN: Qualitative free-text questions were embedded in a large multi-country, cross-sectional survey, to explored fathers' attendance, participation, and experience of health care during appointments with their pregnant partner and/or baby. SETTING AND PARTICIPANTS: Expectant and new fathers were recruited through Prolific®, an international paid online survey platform. FINDINGS: Qualitative responses (n=889) were provided by fathers from 28 countries, with experiences of a range of contexts and models of care; 46.8% of whose partners were pregnant and 53.2% had given birth since 2020. The findings suggest that although most fathers wanted to attend and participate in maternity and early parenting-related healthcare, multiple barriers were identified at the individual father, organisational context, and societal levels. Fathers reported negative social factors such as gender bias and restrictive gender norms as barriers to their healthcare engagement. In contrast, factors that enabled fathers to overcome barriers included the fathers' feelings of confidence in their partner's autonomy and decision-making skills, trusted professional relationships with clinicians, and clinicians with good interpersonal skills. KEY CONCLUSIONS: Multiple barriers restrict the participation of fathers in healthcare for childbearing and early parenting. Knowledge of these barriers can inform healthcare redesign to include more successful engagement strategies for fathers, to benefit fathers, mothers, and infants alike. IMPLICATIONS FOR PRACTICE: Health professionals consulting with the mother, father and infant triad are ideally placed to address the healthcare needs of both parents. Early engagement of fathers in family health care by use of inclusive interpersonal skills and the development of a trusted relationship has potential to improve paternal mental health, and may be associated with benefits for the health, wellbeing and safety of the whole family.

Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium.

PURPOSE: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. METHODS: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. RESULTS: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of - 6.4%-points (95% confidence interval [CI] - 12.8%-points to - 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI - 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI - 9.3 to 17.5; P = 0.142) for EQ VAS. CONCLUSIONS: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.

Investigating allied health professionals' attitudes, perceptions and acceptance of an electronic medical record using the Unified Theory of Acceptance and Use of Technology.

Objective This study aimed to investigate allied health professionals' (AHPs') perspectives pre- and post-implementation of an electronic medical record (EMR) in a tertiary health service in Australia and examine factors influencing user acceptance. Methods Data were collected pre- and post-EMR implementation via cross-sectional online surveys based on the Unified Theory of Acceptance and Usage of Technology (UTAUT). All AHPs at a large tertiary hospital were invited to complete the surveys. Data analysis included descriptive analysis, Mann-Whitney U tests for pre-post item- and construct-level comparison and content analysis of free-text responses. The theoretical model was empirically tested using partial least squares structural equation modelling. Results AHPs had positive attitudes toward EMR use both pre- and post-implementation. Compared to pre-implementation, AHPs felt more positive post-implementation about system ease of use and demonstrated decreased anxiety and apprehension regarding EMR use. AHPs felt they had adequate resources and knowledge to use EMR and reported real-time data accessibility as a main advantage. Disadvantages of EMR included an unfriendly user interface, system outages and decreased efficiency. Conclusions As AHPs increase EMR system familiarity, their positivity towards its use increases. An understanding of what influences AHPs when implementing new compulsory technology can inform change management strategies to improve adoption.

Higher versus lower oxygenation targets in adult ICU patients: A rapid practice guideline.

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) was to provide evidence-based clinical guidance about the use of higher versus lower oxygenation targets for adult patients in the intensive care unit (ICU). The guideline panel comprised 27 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines, including the use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and used the Evidence-to-Decision framework to generate recommendations. A recently published updated systematic review and meta-analysis constituted the evidence base. Through teleconferences and web-based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, equity, feasibility, acceptability, and research priorities. The updated systematic review and meta-analysis included data from 17 randomized clinical trials with 10,248 participants. There was little to no difference between the use of higher versus lower oxygenation targets for all outcomes with available data, including all-cause mortality, serious adverse events, stroke, functional outcomes, cognition, and health-related quality of life (very low certainty of evidence). The panel felt that values and preferences, costs and resources, and equity favored the use of lower oxygenation targets. The ICM-RPG panel issued one conditional recommendation against the use of higher oxygenation targets: "We suggest against the routine use of higher oxygenation targets in adult ICU patients (conditional recommendation, very low certainty of evidence). Remark: an oxygenation target of SpO2 88%-92% or PaO2 8 kPa/60 mmHg is relevant and safe for most adult ICU patients."

Danish men's experiences of cardiovascular screening and their views on preventive cardiovascular medication: A qualitative explorative nurse study.

OBJECTIVES: This study explored Danish men's experience of participating in a screening program for cardiovascular disease (CVD) and their perceptions of preventive medication for CVD before and after participation in the screening program. METHODS: An exploratory phenomenological-hermeneutical study. Fifteen men from a cardiovascular screening program for men aged 65-74 years participated. Semi-structured interviews were conducted before screening and one year later (2015-2017). The interviews were transcribed verbatim and analysed using Kvale and Brinkmann's approach to data analysis. RESULTS: Two main themes were identified: (i) seeking confirmation and control of health: familiarity with CVD; understanding the screening program; confirmation of health; perception of preventive medication, and (ii) sense of own health and prevention: experiences with the screening program; accept or denial of diagnosis and preventive medication. CONCLUSION: A minority of the men understood the nature of the diseases for which they were being examined. The invitation for screening and the outcome of the examinations must be communicated more skilfully. The health providers need to engage early in treatment after the screening and provide an individualised plan that addresses patients concerns and knowledge based on their needs.

Co-design of a question prompt list about pregnancy and childbearing for women with polycystic kidney disease: an exploratory sequential mixed-methods study.

BACKGROUND: Although women with polycystic kidney disease (PKD) generally have healthy pregnancies and babies, pregnancy is associated with a greater risk of maternal complications and requires planning and management of their condition. Given these possible complications, routine communication about childbearing between women with PKD and their treating team is important. A question prompt list (QPL), a structured list of questions used by patients during consultations with healthcare providers, may be beneficial in assisting women with PKD to discuss their childbearing concerns with, and seek related information from, their treating team. The aims of this study were to co-design a QPL about pregnancy and childbearing for women with PKD, and evaluate its comprehensibility, salience, and acceptability. METHODS: An exploratory sequential mixed-methods study of women of reproductive age with PKD living in Australia, using an experience-based co-design approach with two phases. Women were recruited from a metropolitan public health service and via social media and invited to complete an anonymous online survey about the development of the PKD QPL (phase one) and participate in an online discussion group about its refinement (phase two). RESULTS: Sixteen women completed the development survey and seven participated in the evaluation discussion group. Participants reported that women with PKD would value and use a QPL to prompt discussions with and seek further information about pregnancy and childbearing from their healthcare providers. Women identified four main topics for the QPL: 'thinking about having a baby', 'pregnancy', 'my medications' and 'after my baby is born'. Within each section a series of questions was developed. Based on the findings, a QPL about pregnancy and childbearing for women with PKD was co-designed. CONCLUSIONS: Women with PKD often find it difficult to access information and have discussions with their health care providers about pregnancy and childbearing. The PKD QPL co-designed in this study was perceived to be an acceptable tool which will, from the perspectives of participants, assist women with PKD to access information more easily about pregnancy, childbearing and PKD; ask more targeted questions of their treating team; and make informed childbearing decisions.

A low-carbohydrate diet in place of SGLT2i therapy in a patient with diabetic cardiomyopathy.

Summary: In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium-glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple 'traffic light' style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced. Learning points: Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes. Low-carbohydrate diets (LCD) mimic many effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i). LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM. LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM. Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

Health literacy among fathers and fathers-to-be: a multi-country, cross-sectional survey.

During pregnancy and early fatherhood, men are at higher risk of poor health, exacerbated by low engagement by healthcare services. Yet the transition to fatherhood presents an opportunity for men to improve their health and health behaviours. Health literacy refers to individuals' competence in accessing and applying health information. Poor health literacy is associated with poor health and low help-seeking. The aim of this study was to identify health literacy strengths, needs and profiles among fathers. Men who were expecting a baby ('antenatal') or had become fathers in the past 18 months ('postnatal') were recruited through an international, online paid survey platform. The survey included the nine-scale Health Literacy Questionnaire (HLQ). Of 889 survey respondents (n = 416, 46.5% antenatal; n = 473, 53.5% postnatal), 274 (31.0%) were residing in the USA and 239 (27.0%) in the UK. Relatively higher scores were reported for HLQ scales relating to having sufficient information and finding and understanding this information, as well as social support for health. Relatively lower scores were obtained for scales relating to actively managing one's own health and navigating the health care system. Three scale scores were significantly lower among nulliparous than multiparous men. Seven health literacy profiles were identified. In conclusion, while fathers have some health literacy strengths, they also experience some barriers, particularly first-time fathers. Awareness of diverse health literacy profiles among fathers may assist in developing strategies to strengthen health services' capacity to meet fathers' needs and reduce risks to their health at this critical juncture in families' lives.

Worsening psychological wellbeing of Australian hospital clinical staff during three waves of the coronavirus (COVID-19) pandemic.

Objective This study aimed to assess and compare the psychological wellbeing of Australian hospital clinical staff at three timepoints during the coronavirus disease 2019 (COVID-19) pandemic. Methods An anonymous, online, cross-sectional survey was conducted at three timepoints during the COVID-19 pandemic (T1: May-June 2020; T2: October-December 2020; T3: November 2021-January 2022). The surveys were completed by nurses, midwives, doctors and allied health staff employed at a large metropolitan tertiary health service located in Melbourne, Australia. The Depression, Anxiety and Stress Scale (DASS-21) assessed respondents' psychological wellbeing in the past week. General linear models were used to measure the effects of survey timepoint on DASS-21 subscale scores, adjusting for selected sociodemographic and health characteristics. Results A total of 1470 hospital clinical staff completed at least one survey (T1: 668 (14.7%), T2: 358 (7.9%) and T3: 444 (9.8%)). Respondents' sociodemographic characteristics were similar across the three timepoints and within professional discipline groups. Respondents' psychological wellbeing was worse at T3 compared to the earlier survey timepoints. Adjusting for respondent characteristics, depression, anxiety and stress scores were significantly higher for respondents of the third survey compared to the first (P < 0.001). Conclusions There was a significant and persistent negative impact on the psychological wellbeing of hospital clinical staff in Australia across waves of the COVID-19 pandemic. Hospital clinical staff would benefit from ongoing and continued wellbeing support during and after pandemic waves.

Platform trials.

Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example.

Effects of a low carbohydrate diet on heart failure symptoms and quality of life in patients with diabetic cardiomyopathy: A randomised controlled trial pilot study.

BACKGROUND AND AIMS: Heart failure, insulin resistance and/or type 2 diabetes mellitus coexist in the syndrome that is diabetic cardiomyopathy. Patients with diabetic cardiomyopathy experience high symptom burden and poor quality of life. We tested the hypothesis that a low carbohydrate diet improves heart failure symptoms and quality of life in patients with diabetic cardiomyopathy. METHODS AND RESULTS: We conducted a 16-week randomised controlled pilot trial comparing the effects of a low carbohydrate diet (LC) to usual care (UC) in 17 adult patients with diabetic cardiomyopathy. New York Heart Association classification, weight, thirst distress and quality of life scores as well as blood pressure and biochemical data were assessed at baseline and at 16 weeks. Thirteen (n = 8 LC; n = 5 UC) patients completed the trial. The low carbohydrate diet induced significant weight loss in completers (p = 0.004). There was a large between-group difference in systolic blood pressure at the end of the study (Hedges's g 0.99[-014,2.08]). There were no significant differences in thirst or quality of life between groups. CONCLUSION: This is the first clinical trial utilising the low carbohydrate dietary approach in patients with diabetic cardiomyopathy in an outpatient setting. A low carbohydrate diet can lead to significant weight loss in patients with diabetic cardiomyopathy. Future clinical trials with larger samples and that focus on fluid and sodium requirements of patients with diabetic cardiomyopathy who engage in a low carbohydrate diet are warranted. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12620001278921. DATE OF REGISTRATION: 26th November 2020.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit.

BACKGROUND: This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'. Supplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been administered liberally, resulting in high proportions of patients with hyperoxemia (exposure of tissues to abnormally high concentrations of oxygen). This has been associated with increased mortality and morbidity in some settings, but not in others. Thus far, only limited data have been available to inform clinical practice guidelines, and the optimum oxygenation target for ICU patients is uncertain. Because of the publication of new trial evidence, we have updated this review. OBJECTIVES: To update the assessment of benefits and harms of higher versus lower fractions of inspired oxygen (FiO2) or targets of arterial oxygenation for adults admitted to the ICU. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, and LILACS. We searched for ongoing or unpublished trials in clinical trial registers and scanned the reference lists and citations of included trials. Literature searches for this updated review were conducted in November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared higher versus lower FiO2 or targets of arterial oxygenation (partial pressure of oxygen (PaO2), peripheral or arterial oxygen saturation (SpO2 or SaO2)) for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language. We excluded trials randomising participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, or PaO2 below 6 kPa) or to hyperbaric oxygen, and cross-over trials and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Four review authors independently, and in pairs, screened the references identified in the literature searches and extracted the data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events (SAEs), and quality of life. We analysed all outcomes at maximum follow-up. Only three trials reported the proportion of participants with one or more SAEs as a composite outcome. However, most trials reported on events categorised as SAEs according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single SAE with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with an SAE in each trial. Two trials reported on quality of life. Secondary outcomes were lung injury, myocardial infarction, stroke, and sepsis. No trial reported on lung injury as a composite outcome, but four trials reported on the occurrence of acute respiratory distress syndrome (ARDS) and five on pneumonia. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single lung injury event with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with ARDS or pneumonia in each trial. We assessed the risk of systematic errors by evaluating the risk of bias in the included trials using the Risk of Bias 2 tool. We used the GRADEpro tool to assess the overall certainty of the evidence. We also evaluated the risk of publication bias for outcomes reported by 10b or more trials. MAIN RESULTS: We included 19 RCTs (10,385 participants), of which 17 reported relevant outcomes for this review (10,248 participants). For all-cause mortality, 10 trials were judged to be at overall low risk of bias, and six at overall high risk of bias. For the reported SAEs, 10 trials were judged to be at overall low risk of bias, and seven at overall high risk of bias. Two trials reported on quality of life, of which one was judged to be at overall low risk of bias and one at high risk of bias for this outcome. Meta-analysis of all trials, regardless of risk of bias, indicated no significant difference from higher or lower oxygenation strategies at maximum follow-up with regard to mortality (risk ratio (RR) 1.01, 95% confidence interval (C)I 0.96 to 1.06; I2 = 14%; 16 trials; 9408 participants; very low-certainty evidence); occurrence of SAEs: the highest proportion of any specific SAE in each trial RR 1.01 (95% CI 0.96 to 1.06; I2 = 36%; 9466 participants; 17 trials; very low-certainty evidence), or quality of life (mean difference (MD) 0.5 points in participants assigned to higher oxygenation strategies (95% CI -2.75 to 1.75; I2 = 34%, 1649 participants; 2 trials; very low-certainty evidence)). Meta-analysis of the cumulated number of SAEs suggested benefit of a lower oxygenation strategy (RR 1.04 (95% CI 1.02 to 1.07; I2 = 74%; 9489 participants; 17 trials; very low certainty evidence)). However, trial sequential analyses, with correction for sparse data and repetitive testing, could reject a relative risk increase or reduction of 10% for mortality and the highest proportion of SAEs, and 20% for both the cumulated number of SAEs and quality of life. Given the very low-certainty of evidence, it is necessary to interpret these findings with caution. Meta-analysis of all trials indicated no statistically significant evidence of a difference between higher or lower oxygenation strategies on the occurrence of lung injuries at maximum follow-up (the highest reported proportion of lung injury RR 1.08, 95% CI 0.85 to 1.38; I2 = 0%; 2048 participants; 8 trials; very low-certainty evidence). Meta-analysis of all trials indicated harm from higher oxygenation strategies as compared with lower on the occurrence of sepsis at maximum follow-up (RR 1.85, 95% CI 1.17 to 2.93; I2 = 0%; 752 participants; 3 trials; very low-certainty evidence). Meta-analysis indicated no differences regarding the occurrences of myocardial infarction or stroke. AUTHORS' CONCLUSIONS: In adult ICU patients, it is still not possible to draw clear conclusions about the effects of higher versus lower oxygenation strategies on all-cause mortality, SAEs, quality of life, lung injuries, myocardial infarction, stroke, and sepsis at maximum follow-up. This is due to low or very low-certainty evidence.

Self-determination theory interventions versus usual care in people with diabetes: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes. METHODS: We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE. RESULTS: Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95% CI -4.85, 4.86, I2 = 0%; 225 participants, 3 trials, TSA-adjusted CI -11.83, 11.83), all-cause mortality, serious adverse events, diabetes distress, depressive symptoms, adverse events, glycated hemoglobulin A1c, or motivation (controlled). The certainty of the evidence was low to very low for all outcomes. We found beneficial effect on motivation (autonomous and amotivation; low certainty evidence). CONCLUSIONS: We found no effect of self-determination-based interventions on our primary or secondary outcomes. The evidence was of very low certainty. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181144.