Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities.

BACKGROUND: Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management. METHODS: In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin. RESULTS: Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference - 1.1%; 95% CI - 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified. CONCLUSIONS: Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.

BACKGROUND: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS: There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02559310.

Vulnerability, Harm, and Compromised Ethics Revealed by the Experiences of Queer Birthing Women in Rural Healthcare.

Phenomenological interviews with queer women in rural Nova Scotia reveal significant forms of trauma experienced during labour and birth. Situating the accounts of participants within both phenomenological and intersectional analyses reveals harms enabled by structurally embedded heteronormative and homophobic healthcare practices and policies. Our account illustrates the breadth and depth of harm experienced and outlines how these violate core ethical principles and values in healthcare.

Rendering LGBTQ+ Visible in Nursing: Embodying the Philosophy of Caring Science.

Although health care institutions continue to address the importance of diversity initiatives, the standard(s) for treatment remain historically and institutionally grounded in a sociocultural privileging of heterosexuality. As a result, lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities in health care remain largely invisible. This marked invisibility serves as a call to action, a renaissance of thinking within redefined boundaries and limitations. We must therefore refocus our habits of attention on the wholeness of persons and the diversity of their storied experiences as embodied through contemporary society. By rethinking current understandings of LGBTQ+ identities through innovative representation(s) of the media, music industry, and pop culture within a caring science philosophy, nurses have a transformative opportunity to render LGBTQ+ visible and in turn render a transformative opportunity for themselves.

'High-risk' pregnancy after perinatal loss: understanding the label.

OBJECTIVE: to explore women's experience of living with a 'high-risk' pregnancy following a perinatal loss. DESIGN: a feminist phenomenological methodology provided the framework for the research study. PARTICIPANTS AND SETTING: the experience of 'high-risk' pregnancy following perinatal loss of seven women receiving care at a tertiary health centre in Atlantic Canada was explored by way of conversational interviews and reflective journaling. FINDINGS: four themes emerged through thematic analysis and researcher interpretation: (1) understanding the meaning in the label of 'high-risk' pregnancy, (2) relational engagement with the unborn infant, (3) insight and acceptance of the influence of previous loss, and (4) essentiality of information. Taken together, these four themes represent the storied text embedded in the research study. The focus of attention in this article is based solely on the first theme, understanding the meaning in the label of 'high-risk' pregnancy, in so far as this fosters an ability to attend to the interpretive text in the methodological manner appropriate to phenomenological inquiry. CONCLUSIONS AND IMPLICATIONS: although previous research indicates that the label of 'high-risk' in pregnancy is often associated with increased anxiety and fear, findings from this study suggest that a 'high-risk' pregnancy following perinatal loss results in women embracing the 'high-risk' label. By recognising the possibility that women experiencing 'high-risk' pregnancy following perinatal loss may perceive the label of 'high-risk' pregnancy in a positive way, nurses, midwives and other health-care providers may begin to alter their practices when caring for these women in current health-care environments.

Wise women: mentoring as relational learning in perinatal nursing practice.

AIMS AND OBJECTIVES: The focus of this paper is on one of four themes from a study exploring mentoring relationships between nurses in the intrapartum setting. The theme, relational learning, highlights how perinatal nurses engage with each other and engage with birthing women on a journey of learning in perinatal nursing practice. BACKGROUND: Few studies have explored the contextual, lived experiences of informal mentoring relationships within nursing, particularly within perinatal nursing. DESIGN: A qualitative feminist phenomenological study that considered a gender-centred, embodied exploration of human lived experiences was conducted. METHOD: Five registered nurses practicing on a tertiary level labour and delivery unit in eastern Canada were purposefully recruited. Data were collected by phenomenological interviews, practice observations in the clinical setting and reflective journaling. RESULTS: Four themes emerged through thematic analysis and researcher interpretation: the meaning of nurse-to-nurse mentoring, mentoring as relational learning, mentoring as embodied learning and a contextual understanding of nurse-to-nurse mentoring. Relational learning came to be understood through feminist phenomenological analysis, which revealed that expert perinatal nursing knowledge develops within positive mentoring relationships between perinatal nurses practicing with birthing women. This learning extends beyond tasks to a holistic understanding of clinical situations within specific health and social contexts. The mentor models positive perinatal nursing practices and creates a sense of enthusiasm that harnesses the raw passion new nurses often have for practice. CONCLUSION: The findings in this study aim to promote the understanding of the importance of relational, experiential learning for perinatal nurses' professional development. RELEVANCE TO CLINICAL PRACTICE: The results from this study will encourage nurses and nurse leaders to support mentoring by providing adequate resources and positive feedback for mentoring relationships. This will foster and sustain expert nurses to support novice nurses in perinatal practice. The findings also offer insight for perinatal practices beyond nursing, including midwifery.

Feminist and queer phenomenology: a framework for perinatal nursing practice, research, and education for advancing lesbian health.

A queer phenomenology would involve an orientation toward queer, a way to inhabit the world that gives "support" to those whose lives and loves make them appear oblique, strange, and out of place. (Ahmed, 2006) The climate of the health care system is a reflection of society, which often hesitates to support individuals who choose paths other than those, that are heteronormatively constructed. Consequences of such limited directedness include fear, misunderstanding, avoidance, and discrimination on the part of nurses toward individuals involved in same-sex partnerships (Goldberg, 2005/2006). A feminist and queer phenomenological framework offers an approach for perinatal nurses to advance lesbian health and, in particular, lesbian couples' experiences of birthing, in the context of nursing practice, research, and education.

Embodied trust within the perinatal nursing relationship.

OBJECTIVES: to explore an experiential understanding of the relationships that perinatal nurses fostered with birthing women within their clinical practices. DESIGN: a feminist phenomenology provided the methodological framework for the research study. PARTICIPANTS/SETTING: interviews were conducted with eight perinatal nurses and eight postpartum women from a low-risk obstetrical hospital in Western Canada. Participant observation was also conducted with the eight nurses after their interviews. FINDINGS: embodied trust, one of the major themes reflected in the research, highlighted the ways in which a trusting relationship with a perinatal nurse simultaneously established a birthing woman's self-trust, thus enabling her to develop her own bodily abilities to birth her baby into the world. CONCLUSIONS: because feminist phenomenology takes seriously the embodied practices of the female subject, this research attends to the practices of women and nurses in ways that other non-feminist or non-experiential methods dismiss or reject. Future research is needed, however, to further explore these relationships in other situations, particularly in places of difference. Only then will nurses, midwives and other perinatal health-care providers have the knowledge required to work with women in empowering and embodying ways during their experiences of birth.

Rethinking the birthing body: Cartesian dualism and perinatal nursing.

AIM OF THE PAPER: This paper highlights the pervasive influence of a Cartesian metaphysics on the medical paradigm and its profound impact on the practice of perinatal nursing in North America. BACKGROUND: Modern perinatal health care practices are founded on a Cartesian metaphysics that reduce birthing women to the status of object. Such practices deny the holistic aims of perinatal nursing. METHODS: A philosophical inquiry informs the tenets of this metaphysical discussion regarding the foundations of perinatal nursing practices. FINDINGS: Although perinatal health care is founded on a Cartesian metaphysics, an alternative paradigm of embodied practice is suggested as a way of viewing birthing women as embodied subjects. CONCLUSION: If the foundations of health care, which have been built on a Cartesian metaphysics, are not re-examined, perinatal nurses will be providing care that further reduce women to the status of object.