COVID MED - An Early Pandemic Trial of Losartan for Hospitalized COVID-19 Patients

Background ACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19. Methods COVID MED was quadruple-blinded, placebo-controlled, multicenter randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint was the NCOSS slope of change. Slow enrollment prompted early stopping. Results Of 432 screened patients, 14 were enrolled (3.5%), 9 received losartan and 5 combined control (lopinavir/ritonavir [N=2], placebo [N=3]); 1 hydroxychloroquine arm patient was excluded. Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in NCOSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan. Conclusions In this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.

Lubricant for Reducing Perineal Trauma: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background Different techniques have been reported to prevent perineal lacerations, but the effects of the use of lubricant have been unclear and is still subject of debate. Objective To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. Search strategy PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang databases, ClinicalTrials.gov in 25 June 2021. Selection criteria Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care in women with cephalic presentation at vaginal delivery were included . Data collection and analysis Two independent reviewers selected eligible trials and extracted data on perineal trauma, duration of the second-stage labor, postpartum hemorrhage and Apgar score for meta-analysis. Main results Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (RR 0.84, 95%CI 0.76 to 0.93), second-degree perineal laceration (RR 0.72, 95%CI 0.64 to 0.82) and episiotomy (RR 0.77, 95%CI 0.62 to 0.96), had a shorter duration of the second-stage labor (MD -13.72 minutes, 95%CI -22.68 to -4.77). Subgroup analysis indicated that women with obstetric gel had a shorter duration of the second-stage (MD -16.9 minutes, 95%CI -27.03 to -6.78 vs MD -8.38 minutes, 95%CI -11.11 to -5.65; P interaction=0.02) when compared with liquid wax. Conclusions Compared with standard care, lubricants could reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor.

Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)—protocol for a randomized clinical trial

Background It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. Design and methods The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. Discussion The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation—patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible—however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Trial registration ISRCTN ISRCTN11536318. Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Nurse-led self-management support after organ transplantation—protocol of a multicentre, stepped-wedge randomized controlled trial

Background Recipients of an organ transplantation face a number of challenges and often need to change their health behaviour. Good self-management skills are essential for optimal clinical outcomes. However, few interventions are available to support post-transplant self-management. To fill this gap, we developed a self-management support intervention offered by nurse practitioners. The primary aim of the study is to implement and test the effectiveness of the ZENN intervention in promoting self-management skills among heart, kidney liver and lung transplant recipients in comparison to standard care. The secondary aim is to assess the self-management support skills of nurse practitioners who will deliver the intervention. Methods This multi-centre stepped-wedge randomized controlled trial will take place from September 2020 until May 2023. All departments will commence with inclusion of patients in the control period. Each department will be randomly assigned to a start date (step in the wedge) to commence the experimental period. Patients in the control period will receive standard care and will be asked to complete questionnaires at baseline (T0), 6 months (T1) and 12 months (T2), to assess self-management, self-regulation, quality of life and adherence. During the experimental period, patients will receive standard care plus the ZENN intervention and receive the same set of questionnaires as participants in the control period. Nurse practitioners will complete a baseline and follow-up questionnaire to assess differences in self-management support skills. Video recordings of outpatient clinic consultations during the control and experimental periods will determine the differences in nurses’ needs-thwarting and needs-supporting skills between the control and experimental period. Discussion The ZENN intervention could be a useful approach to support patients’ self-management skills after organ transplantation and thus promote clinical outcomes as well as avoid adverse events. Trial registration Dutch Trial Register NL8469. Registered on March 19, 2020.

Impact of a mobile application for tracking nausea and vomiting during pregnancy (NVP) on NVP symptoms, quality of life, and decisional conflicts regarding NVP treatments: the MinSafeStart randomized controlled trial (Preprint)

BACKGROUND Pregnant women are active users of mobile applications (app) for health purposes. These apps may improve self-management of health-related conditions. Up to 70% of pregnant women experience nausea and vomiting (NVP). Even mild NVP can significantly reduce the quality of life (QoL), and it can become an economic burden for both the woman and society. NVP often occurs before the first maternal care visit; therefore, apps can potentially play an important role in empowering pregnant women to recognize, manage, and seek appropriate treatment for NVP, when required. OBJECTIVE This study investigated whether the MinSafeStart mobile application (MSS app) could impact NVP-related symptoms, QoL, and decisional conflicts regarding NVP treatment. METHODS This randomized controlled trial enrolled 222 pregnant women with NVP in Norway from 2019-2020. The intervention group had access to the MSS app, which could be used to track NVP symptoms and access tailored advice. NVP severity was rated with the Pregnancy Unique Quantification of Emesis (PUQE) score. The control group followed standard maternal care. We collected data on maternal baseline characteristics, NVP severity, QoL, and decisional conflicts with two sets of online questionnaires. One set of questionnaires was completed at enrollment, and the other was completed after two weeks. We performed linear regression analyses to explore whether the use of the MSS app was associated with NVP severity, QoL, or decisional conflicts. RESULTS Among the 222 women enrolled in the study, 192 (86.5%) completed the baseline questionnaires and were randomized to either the intervention (n=89) or the control group (n=103). In the intervention group, 88 women downloaded the app, and 468 logs were recorded. In both groups, women were enrolled at a median of 8 gestational weeks. At baseline, the average PUQE scores were 4.9 and 4.7; the average QoL scores were 146 and 149; and the average decisional conflict scores were 40 and 43, in the intervention and control groups, respectively. The app had no impact on NVP severity (aβ: 0.6, 95% Cl: -0.1, 1.2), QoL (aβ: -5.3; 95% Cl: -12.5, 1.9), or decisional conflicts regarding NVP treatment (aβ: -1.1, 95% Cl -6.2, 4.2), compared to standard care. CONCLUSIONS Tracking NVP symptoms with the MSS app was not associated with improvements in NVP symptoms, QoL, or decisional conflicts after two weeks, compared to standard care. Future studies should include a process evaluation to improve our understanding of how pregnant women use the app and how to optimize its utility within maternity care. Specifically, studies should focus on how digital tools might facilitate counseling and communication between pregnant women and health care providers, regarding NVP management during pregnancy. CLINICALTRIAL This trial was registered at ClinicalTrails.gov (identifier: NCT04719286, registration date: January 22, 2021).

Impact of an Ambulatory Monitoring System on Deterioration Detection and Clinical Outcomes in Hospitalised Patients. A Feasibility Randomised Controlled Trial Protocol.

BackgroundDespite the exponential growth of wearable technology, previous research indicates a lack of statistically significant evidence to support the hypothesis that implementation of wearable ambulatory vital sign monitoring systems impact early patient deterioration detection and clinical outcomes. This highlights the need for large, rigorous studies to address this gap. The objective of this feasibility trial is to assess the impact of an ambulatory monitoring system (AMS) on deterioration detection and clinical outcomes in hospitalised patients, compared to standard care. As a secondary objective we will assess the feasibility of conducting a full randomised controlled trial (RCT).MethodsBetween 120 and 240 patients will be recruited and randomised equally to either an AMS or standard care group. Wearable devices will include a pulse oximeter (monitoring pulse rate and oxygen saturation), a chest patch (monitoring heart rate, respiratory rate and temperature) and a wireless blood pressure cuff (monitoring systolic and diastolic blood pressure). Both groups will wear the devices during their ward length of stay, however only data and alerts from the AMS group will be visible to clinical staff.DiscussionRecruitment of participants is expected to start in January 2022, with an anticipated completion date of December 2022. This feasibility RCT will test the early impact of our AMS implementation in a non-intensive care ward and provide data to support the design and deployment of a full RCT which will provide much-needed evidence of the impact of AMS on early deterioration detection and clinical outcomes.

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were ‘Alive without type 2 diabetes’, ‘Alive with type 2 diabetes’ and ‘Dead’. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.