Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Factors Related to the Professional Management of Early Breastfeeding Problems: Perspectives of Lactation Consultants

Addressing the sub-optimal breastfeeding initiation and duration rates has become a national priority. Inadequate support for addressing early breastfeeding challenges is compounded by a lack of collaboration between providers such as lactation professionals, nurses, pediatricians, and the family. The purpose of this exploratory study was to understand International Board Certified Lactation Consultants\u27 (IBCLCs) perceived barriers to managing early breastfeeding problems. This qualitative study was guided by the symbolic interactionist framework through a grounded theory methodological approach. In-depth interviews were conducted with 30 IBCLCs from across Florida. IBCLCs were from a range of practice settings, including hospitals, WIC clinics, private practice, and pediatric offices. Data were digitally recorded, transcribed, and analyzed in Atlas.ti. A range of barriers were identified and grouped into the following categories: indirect barriers such as social norms, knowledge, attitudes; direct occupational barriers such as institutional constraints, lack of coordination, and poor service delivery; and direct individual barriers including social support and mother\u27s self-efficacy. A model was developed to illustrate the factors that influence the role enactment of IBCLCs in terms of managing breastfeeding problems. IBCLCs overwhelmingly wish to be perceived as valued members of a health care team, but often find interprofessional collaboration is a struggle. However, IBCLCs find creative strategies to navigate challenges and describe their role as pivotal in empowering mothers and their families to meet their breastfeeding goals. Though rarely actualized, IBCLCs place strong value on coordinated, team approaches to breastfeeding management that employ transparent communication between providers and focus on empowering and educating mothers. Strategies for better collaboration and communication between IBCLCs and other providers are needed. Findings provide insight into the management issues of early breastfeeding problems and may lead to future interventions to reduce early weaning, thus increasing the lifelong health benefits of breastfeeding to the infant and mother

A Feminist Perspective on the Precautionary Principle and the Problem of Endocrine Disruptors under Neoliberal Globalization Policies

Industrialization and development during the last 200 years have led to an increase of pesticides, an intensified use of synthetic chemicals, higher levels of environmental pollution, and more exposure to hazardous working conditions. Environmental toxins, many of which are endocrine disruptors, are stored in fat tissue, increasing reproductive health risks for both women and men. Women’s bodies are particularly vulnerable as sites for creating, growing, feeding, and nurturing the next generation. And yet, women’s lives are consistently devalued, especially in a capitalist economy, so that a woman’s rights to her own reproductive health are no longer guaranteed. In this thesis I first review ecological destruction, environmental policies, and food safety/security issues for women. I then examine neoliberal globalization as an active participant in the destruction of the environment and an attack on global health. I discuss how utilizing feminist theory effectively, and actively, will ensure women the right to their health. I employ postmodern feminist and refigured ecofeminist theory to demonstrate how a feminist perspective is necessary in the development of policies that address the problem of endocrine disruptors in terms of women’s reproductive health and the health of future generations. Finally, I suggest that the precautionary principle must include a feminist perspective to fully succeed

Listening to Voices and Visualizing Data in Qualitative Research

One of the tenets of qualitative research is the emphasis and honoring of the participants’ own words as generative of meaning and knowledge; yet it is rare to hear the actual voices of the research participants in a presentation or in text. Qualitative research dissemination has relied on dense transcribed text; these “mountains of words” do not lend themselves to the space limitations of academic journals or condensed visual elements such as summary charts, tables, or graphs. Technological advancements have the potential to revolutionize dissemination efforts, especially for qualitative research. The use of audio clips in poster and oral presentations, as well as embedded within written manuscripts plays with the interstices between the research participants and the observer. Infograms are effective ways of conveying a story visually. We demonstrate how combining audio clips and infographics can be a unique hypermodal dissemination possibility for qualitative results

Lactation Consultants’ Perceived Barriers to Providing Professional Breastfeeding Support

Background: Addressing suboptimal breastfeeding initiation and duration rates is a priority in the United States. To address challenges to improving these rates, the voices of the providers who work with breastfeeding mothers should be heard. Research Aim: The purpose of this study was to explore lactation consultants’ perceived barriers to managing early breastfeeding problems. Methods: This qualitative study was conducted with a grounded theory methodological approach. In-depth interviews were conducted with 30 International Board Certified Lactation Consultants across Florida. Lactation consultants were from a range of practice settings, including hospitals, Special Supplemental Nutrition Program for Women, Infants, and Children clinics, private practice, and pediatric offices. Data were digitally recorded, transcribed, and analyzed in Atlas.ti. Results: A range of barriers was identified and grouped into the following categories/themes: indirect barriers (social norms, knowledge, attitudes); direct occupational barriers (institutional constraints, lack of coordination, poor service delivery); and direct individual barriers (social support, mother’s self-efficacy). A model was developed illustrating the factors that influence the role enactment of lactation consultants in managing breastfeeding problems. Conclusion: Inadequate support for addressing early breastfeeding challenges is compounded by a lack of collaboration among various healthcare providers and the family. Findings provide insight into the professional management issues of early breastfeeding problems faced by lactation consultants. Team-based, interprofessional approaches to breastfeeding support for mothers and their families are needed; improving interdisciplinary collaboration could lead to better integration of lactation consultants who are educated and experienced in providing lactation support and management of breastfeeding problems