FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer.

On July 26, 2021, the FDA granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple-negative breast cancer. Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared with the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively [HR: 0.63, 95% confidence interval (CI), 0.48-0.82, P = 0.00031]. Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI, 1.6-13.4). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit-risk assessment.

Music Therapy for Children with Oncology & Hematological Conditions and Their Families: Advancing the Standards of Psychosocial Care.

Background: Diagnosis and treatment of cancer and blood disorders in childhood, adolescence and young adulthood has a significant impact on patients and families. The Psychosocial Standards of Care project, initiated in 2012, resulted in 15 Psychosocial Standards (PSS) that guide the care patients and families receive throughout treatment. As members of the multidisciplinary psychosocial care team, music therapists play an important role in the advancing the PSS. Most surveys have focused on other commonly provided services (e.g., social work, child life), leaving gaps in our understanding about the availability and use of music therapy services to advance PSS. This paper offers an initial description of how music therapy services contribute to the provision of care under these Standards. Methods: We analyze how music therapy services promote PSS through synthesis of a music therapy clinical practice survey, published literature, and scope of practice documents. A brief overview of music therapy services structure, PSS that music therapy services currently address, and two clinical program descriptions are included. Results: Music therapy services address 9 of the 15 PSS and are well integrated within the larger program of psychosocial care. Findings suggest integration of music therapy services can help ensure personalized, comprehensive care and efficient use of often-limited psychosocial care resources. Discussion: Nurses, as members of the psychosocial and medical teams are uniquely positioned to identify patient and family care needs and refer patients for services. Understanding how music therapy services address PSS and most importantly, the needs of patients and families, will optimize their care.

Envelope characteristics in individuals who developed neutralizing antibodies targeting different epitopes in HIV-1 subtype C infection.

Broadly neutralizing antibodies (bNAbs) may constitute an essential component of a protective vaccine against HIV-1, yet no immunogen has been able to elicit them. To characterize the development of bNAbs in HIV-1 subtype C infected individuals, a panel of 18 Env-pseudotyped viruses was used to screen 18 study participants. The specificity of plasma neutralization was mapped against Env mutants and MPER chimeras. Envelope (env) gene sequence evolution was characterized by single genome amplification and sequencing. Three out of eighteen individuals developed broad plasma neutralizing activity (>60% breadth). Two of the three participants may target epitopes comprising glycans at position 276 of the D loop in the CD4 binding site and 332 glycan supersite, respectively. Deletion of these glycans was associated with neutralization resistance. Our study describes the kinetics of the development of plasma neutralizing activity and identified amino acid residue changes suggestive of immune pressure on putative epitopes. The study enhances our understanding of how neutralization breadth develops in the course of HIV-1 subtype C infection.

Music Therapist Experiences of a Randomized Controlled Trial as Clinician Researchers.

Music therapy clinicians bring an important perspective to the design and conduct of clinically meaningful studies. Unfortunately, there continue to be roadblocks that hinder clinician involvement in research and the development of successful partnerships between academic researchers and practicing clinicians. To help grow clinician involvement, it is important that research teams share their experiences. As such, the purpose of this qualitative study was to share music therapists' perspectives about their experience of working as a research clinician on a large multisite randomized controlled trial. 10 board-certified music therapists provided written responses to 6 data-generating questions about: (a) reasons for participating, (b) perceived challenges and benefits, (c) experiences of quality assurance monitoring, (d) professional growth, (e) value of research, and (f) advice for clinicians considering research involvement. Using thematic content analysis, we identified primary themes and subthemes for each question (20 themes; 30 subthemes). Qualitative analysis revealed not only common challenges, such as reconciling clinical and research responsibilities, but also benefits, including continued professional growth, greater understanding of research processes, and research participation as a way to advocate and advance the profession. Finally, for clinicians interested in becoming involved in research, therapists noted the importance of having workplace support from a mentor, supervisor, and/or administrator; seeking out available resources; and knowing roles and responsibilities before initiating research involvement. Findings offer important insight and recommendations to support the involvement of clinicians in research and support further exploration of clinician involvement in dissemination efforts to improve translation and uptake of research into practice.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer.

On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDx BRCA test (Foundation Medicine, Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation-associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 patients with ovarian cancer treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% [57/106; 95% confidence interval (CI), 44-64], and median duration of response was 9.2 months (95% CI, 6.6-11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (≥20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res; 23(23); 7165-70. ©2017 AACRSee related commentary by Kohn et al., p. 7155.

The nurse as bricoleur in falls prevention: learning from a case study of the implementation of fall prevention best practices.

BACKGROUND: Falls prevention in "real-life" clinical practice is a complex undertaking. Nurses play an active and essential role in falls prevention. AIM: This discussion paper presents a picture of the nurse as a bricoleur in falls prevention, requiring knowledge in many areas and the ability to perform multiple diverse tasks. METHODS: Building on a qualitative case study with nurses at various levels in three acute care facilities, this paper posits that the concept of nurse as bricoleur has the potential to broaden our understanding of the complexity of falls prevention. FINDINGS: The nurse as bricoleur within the Promoting Action Research in Health Services framework as the provider of person- or patient-centered evidence-based care is conceptualized. Within this framework, the nurse uses his or her professional knowledge or clinical experience while considering research, local data, and information, and the patient's experience and preferences to provide this care, the bricolage. Each of these areas is discussed as well as the impact on the nurse when a fall does occur. LINKING EVIDENCE TO ACTION: Recognizing this complexity of the nurses' world has important implications for both service delivery and education, including preparation of students, and the implementation of new organizational initiatives and supports for nurses when falls do occur despite the best efforts of all involved.

Using Stake's qualitative case study approach to explore implementation of evidence-based practice.

Although the use of qualitative case study research has increased during the past decade, researchers have primarily reported on their findings, with less attention given to methods. When methods were described, they followed the principles of Yin; researchers paid less attention to the equally important work of Stake. When Stake's methods were acknowledged, researchers frequently used them along with Yin's. Concurrent application of their methods did not take into account differences in the philosophies of these two case study researchers. Yin's research is postpositivist whereas Stake's is constructivist. Thus, the philosophical assumptions they used to guide their work were different. In this article we describe how we used Stake's approach to explore the implementation of a falls-prevention best-practice guideline. We focus on our decisions and their congruence with Stake's recommendations, embed our decisions within the context of researching this phenomenon, describe rationale for our decisions, and present lessons learned.

The real world journey of implementing fall prevention best practices in three acute care hospitals: a case study.

BACKGROUND: Globally, falls are the second leading cause of unintentional injury. In Canada, falls that occur in hospitals have been ranked second as an area of patient safety concern. Many Canadian hospitals seeking to achieve patient safety, accreditation and resource containment goals are implementing evidence-based practices in fall prevention. However, best practices are reported to be only variably effective in reducing hospital fall rates, indicating a potential gap in our understanding of the implementation process. This study was designed to provide insight into the real world of implementation of best practices in fall prevention in acute care Canadian hospitals. APPROACH: Using case study methodology, ninety-five administrative and point-of-care nurses at three hospitals participated in interviews or focus groups and provided documents and artifacts that described their implementation of a falls prevention guideline. FINDINGS AND IMPLICATIONS: Four recommendations with potential to guide others in fall prevention were identified: (1) the need to listen to and recognize the expertise and clinical realities of staff, (2) the importance of keeping the implementation process simple, (3) the need to recognize that what seems simple becomes complex when meeting individual patient needs, and (4) the need to view the process as one of continuous quality improvement.

Randomised controlled feasibility trial of an evidence-informed behavioural intervention for obese adults with additional risk factors.

BACKGROUND: Interventions for dietary and physical activity changes in obese adults may be less effective for participants with additional obesity-related risk factors and co-morbidities than for otherwise healthy individuals. This study aimed to test the feasibility and acceptability of the recruitment, allocation, measurement, retention and intervention procedures of a randomised controlled trial of an intervention to improve physical activity and dietary practices amongst obese adults with additional obesity related risk factors. METHOD: Pilot single centre open-labelled outcome assessor-blinded randomised controlled trial of obese (Body Mass Index (BMI)≥30 kg/m2) adults (age≥18 y) with obesity related co-morbidities such as type 2 diabetes, impaired glucose tolerance or hypertension. Participants were randomly allocated to a manual-based group intervention or a leaflet control condition in accordance to a 2∶1 allocation ratio. Primary outcome was acceptability and feasibility of trial procedures, secondary outcomes included measures of body composition, physical activity, food intake and psychological process measures. RESULTS: Out of 806 potentially eligible individuals identified through list searches in two primary care general medical practices N = 81 participants (63% female; mean-age = 56.56(11.44); mean-BMI = 36.73(6.06)) with 2.35(1.47) co-morbidities were randomised. Scottish Index of Multiple Deprivation (SIMD) was the only significant predictor of providing consent to take part in the study (higher chances of consent for invitees with lower levels of deprivation). Participant flowcharts, qualitative and quantitative feedback suggested good acceptance and feasibility of intervention procedures but 34.6% of randomised participants were lost to follow-up due to overly high measurement burden and sub-optimal retention procedures. Participants in the intervention group showed positive trends for most psychological, behavioural and body composition outcomes. CONCLUSIONS: The intervention procedures were found to be acceptable and feasible. Attrition rates were unacceptably high and areas for improvements of trial procedures were identified. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN90101501.

Re-hospitalizations after myocardial infarction on Prince Edward Island: analysis of the reasons.

In the province of Prince Edward Island (PEI), which has a small homogeneous population of approximately 140,000 people, cardiovascular disease is the leading cause of death accounting for 37% of the total deaths. Next to Newfoundland, this province ranks second highest in Canada for its incidence of cardiovascular disease. This high incidence of cardiovascular disease in this population has been attributed to smoking, physical inactivity, hypertension and obesity. In examining provincial comparisons across Canada, PEI has the highest proportion of physically inactive adults at 68%. PEI has the second highest proportion of adults, 15 years and older, who are daily or occasional smokers at 65% and who have high blood pressure at 12%. PEI has the third highest proportion of adults who are overweight. At the Queen Elizabeth Hospital in Charlottetown, PEI, where the researcher has conducted her study, during the period of January 1997 and December 1997, 192 patients were admitted with the diagnosis of acute myocardial infarction (AMI). The average length of stay in hospital for these patients was 10.3 days. This is high compared to the national average of 6.6 days in hospital. During a one year period, 111 of these 192 patients were re-admitted to hospital with a related cardiovascular diagnosis. This equates to a 57.8% readmission rate for post MI patients. These re-hospitalizations are both costly to health care and disruptive to the quality of life of the individual and his or her family. There is evidence that a portion, approximately 50% of these re-hospitalizations, are due mainly to psychosocial factors and not to unavoidable clinical reasons. A cross-sectional design representing this one year period was used in a chart audit with an analysis done to determine factors associated with re-hospitalization of post MI patients. This article will offer insight regarding the results of this analysis as well as future recommendations for patients being discharged home follow an AMI. The significance of the research lies in its collection of data focusing on behaviors and attitudes around cardiovascular risk factor modification which will enable effective planning and evaluation of health promotion programs, policies, and legislation.