Randomized Double-Blind Study of the Safety and Immunogenicity of Standard-Dose Trivalent Inactivated Influenza Vaccine versus High-Dose Trivalent Inactivated Influenza Vaccine in Adult Hematopoietic Stem Cell Transplantation Patients.

Hematopoietic stem cell transplantation (HCT) survivors are less likely than matched healthy controls to mount a strong immune response to trivalent inactivated influenza vaccine (TIV). High-dose (HD) or standard-dose (SD) TIV were given to adult HCT subjects 18 years or older at least 6 months after transplantation. Subjects were randomized 2:1 to receive either the HD (60 µg hemagglutinin [HA]/strain/dose) or the SD (15 µg HA/strain/dose) TIV. Injection-site and systemic reactions were documented after each vaccination and immune responses were measured before and after each vaccination. A total of 44 subjects were enrolled (25 in year 1 and 19 in year 2), with 15 in the SD group and 29 in the HD group. The median time to vaccination after transplantation was 7.9 months (range, 6 to 106 months), the median age was 50 years (range, 19.6 to 73 years), and 61% were male. No differences in demographic or lab data were noted between groups; however, the HD group had higher median baseline total IgG level (676 versus 469 mg/dL, P = .025). No differences in individual injection-site or systemic reactions were noted between groups; however, more events of any injection-site symptom combined were reported in the HD group. No serious adverse events were attributed to vaccination. After vaccination, the HD group had a higher percentage of individuals with titers ≥1:40 and a higher geometric mean titer (GMT) against the H3N2 strain compared with that of the SD group. HD and SD TIV were found to be safe and well tolerated in adult HCT recipients. However, the HD group had higher frequency of injection-site reactions but the majority of the reactions were mild and resolved. The HD group had a higher percentage of individuals with post-vaccination titer ≥ 1:40 and GMT for H3N2 antigen, indicating better immunogenicity. These data support the need for a phase II immunogenicity trial in HCT recipients.

Geographic distance is not associated with inferior outcome when using long-term transplant clinic strategy.

The optimal healthcare model for follow-up of allogeneic hematopoietic stem cell transplantation (HSCT) recipients after day 100 is not clear. We previously demonstrated that longitudinal follow-up at the transplant center using a multidisciplinary approach is associated with superior survival. Recent data suggest that increased distance from the transplant center is associated with inferior survival. A dedicated long-term transplant clinic (LTTC) was established in 2006 at our center. We hypothesized that geographic distance would not be associated with inferior outcome if patients are followed in the LTTC. We studied 299 consecutive patients who underwent HSCT and established care in an LTTC. The median distance from the transplant center was 118 miles (range, 1 to 1591). The 75th percentile (170 miles) was used as the cut-off to analyze the impact of distance from the center on outcome (219 patients ≤ 75th percentile; 80 patients >75th percentile). The 2 groups were balanced for pretransplant characteristics. In multivariate analyses adjusted for donor type, Center for International Blood and Marrow Transplant Research risk, and transplant regimen intensity, distance from transplant center did not impact outcome. Our study suggests that geographic distance from the transplant center is not associated with inferior outcome when follow-up care is delivered via a dedicated LTTC incorporating well-coordinated multidisciplinary care.

Decision-Making in Surgery.

Surgeons face unique challenges in perioperative decision-making and communication with patients and families. In cardiothoracic surgery, the stakes are high, life and death decisions must be made quickly, and surgeons often lack a longstanding relationship with patients and families prior to intervention. This review considers specific challenges in the preoperative period followed by those faced postoperatively. While preoperative deliberation and informed consent focus on reaching a decision between 2 or more alternative approaches, the most vexing postoperative decisions often involve the patient's discontent with the best-case outcome or how to ensure goal-concordant care when complications arise. This review explores the preoperative ethical and legal requirement for informed consent by describing the contemporary preferred method, shared decision-making. We also present a framework to optimize surgeon communication and promote patient and family engagement in the setting of high-risk surgery for older patients with serious illness. In the postoperative period the family is often tasked with deciding what to do about major complications when the patient has lost decision-making capacity. We discuss several examples and offer strategies for surgeons to navigate these challenging situations. We also explore the concepts of clinical heroism and futility in relation to communicating with patients and families about the outcomes of surgery. Persistent ethical challenges in decision-making suggest that surgeons should improve their skills in communicating with patients to better engage with them, both before and after surgery.

New allergies after cord blood transplantation.

BACKGROUND AIMS: Umbilical cord blood transplantation (CBT) is an effective treatment for benign and malignant diseases. Late effects of CBT are not well described in the literature. In the present study, we present our experience of new-onset allergies in long-term survivors after CBT. METHODS: After an initial patient had a severe peanut allergic reaction after CBT, all CBT patients were prospectively followed for new allergy development. Fifty patients received CBT between March 2006 and June 2011. RESULTS: The median follow-up after CBT was 447 days (range, 12-2022). At the time of analysis, 30 patients were alive, with 3-year survival of 55.5%; median follow-up of surviving patients was 910 days (range, 68-2022). The allergic syndrome developed in five patients, with the cumulative incidence of new allergies at 2 years of 18.4% (95% confidence interval, 10.8-26). The median time to onset of new allergy after transplantation was 298 days (range, 250-809). CONCLUSIONS: Allergy development has been linked to a delayed maturation of the immune system in several studies. We present the first case series of patients who had new allergies after CBT. Further study of this novel complication as well as counseling of patients after CBT would be important.

Menopause knowledge and education in women under 40: Results from an online survey.

BACKGROUND: All women experience the menopause, yet education around the topic is limited. Studies conducted in women aged over 40 show that women have limited knowledge about the menopause. OBJECTIVES: This study aims to understand what women under 40 know about the menopause, how they have acquired this knowledge and where they think menopause education should be taught. This data will help to determine how to effectively deliver menopause education. DESIGN: A survey was designed that asked women under 40 what they know of, and their attitudes to, the menopause, using Qualtrics XM software. METHODS: The survey was advertised for 5 weeks on social media. Six questions related to menopause education were analysed. Responses between age groups under 20, 21-30 and over 30 were compared using a chi-square test. A thematic-style analysis was also conducted on a free-text question where answers referred to education. RESULTS: A total of 738 women's responses were included in the analysis; over 80% had no knowledge or just some knowledge of the menopause. Women over 30 used official websites (p = 0.017) and scientific literature (p = 0.047) significantly more than other age groups to learn about the menopause, while women under 20 were more likely to learn from family members (p = 0.002). These women felt education should start in schools. CONCLUSION: Many women under 40 have limited education of the menopause. Women under 20 are more passive in their approach to learning about the menopause compared with those over 30, who are more proactive. Menopause education strategies must start at school and extend beyond schools adopting a multifaceted approach; it is recommended that the workplace, social media and public health campaigns are used to deliver menopause education moving forward.

Shared Decision-Making in Palliative Care: A Maternalistic Approach.

During goals of care conversations, palliative care clinicians help patients and families determine priorities of care and align medical care with those priorities. The style and methods of communicating with families and negotiating a care plan can range from paternalistic to entirely patient driven. In this paper, we describe a case in which the palliative care clinician approached decision-making using a paradigm that is intuitive to many clinicians and which seems conceptually sound, but which has not been fully explored in the bioethics literature. This paradigm, termed maternalism, allows the clinician to direct decision-making within a relationship such that best interests and autonomy are mutually reinforced, thus reflecting relational autonomy as opposed to individual autonomy. We explore whether this method is appropriate in this case and explain how it captures significant ethical features of the case that might be missed by other approaches.

Palliative Care and Rapid Emergency Screening Tool and the Palliative Performance Scale to Predict Survival of Older Adults Admitted to the Hospital From the Emergency Department.

BACKGROUND: The Palliative Care and Rapid Emergency Screening (P-CaRES) tool has been validated to identify patients in the emergency department (ED) with unmet palliative care needs, but no prognostic data have been published. The Palliative Performance Scale (PPS) has been validated to predict survival based on performance status and separately has been shown to predict survival among adults admitted to the hospital from the ED. OBJECTIVE: To concurrently validate the 6-month prognostic utility of P-CaRES with a replication of prior studies that demonstrated the prognostic utility of the PPS among adults admitted to the hospital from the ED. DESIGN: Prospective cohort study. SETTING/SUBJECTS: Adults >55 years admitted to the hospital from the ED at an urban academic hospital in South Carolina. MEASUREMENT: Baseline PPS score and P-CaRES status were evaluated within 51 hours of admission. Vital status at 6 months was evaluated by phone or chart review. RESULTS: 131 of 145 participants completed the study. Six-month survival was 79.2% of those with a PPS of 60-100 (22/106 died) and 48% of those with a PPS of 10-50 (13/25 died) (p = 0.0004). Six-month survival was 85.2% for P-CaRES negative (13/88 died) and 48.8% for P-CaRES positive (22/43 died) (p < 0.0001). The inferred hazard ratio (HR) for PPS 10-50, as compared to PPS 60-100 was 3.003 (95%CI (1.475, 6.112) p = 0.0024) and the HR for P-CaRES positive, as compared to P-CaRES negative was 4.186 (95%CI (2.052, 8.536) p < 0.0001). CONCLUSION: The P-CaRES tool and PPS can predict 6-month survival of older adults admitted from the ED.

Responsibility for Structural Racism in Medicine: Reflections and Recommendations from One Institution.

In this article, we draw upon recent ethical arguments by Zheng and Young to explain our experience applying the social connection model of responsibility to structural racism in medicine. We propose that taking responsibility for structural racism must begin with acknowledging, studying, and learning from localized, particular instances of racism. Such practices raise personal and institutional consciousness about racism and injustice, creating a knowledge base from which effective action is possible. We describe our experiences engaging with responsibility for structural racism as a small group of scholars dedicated to learning more about our institution's history and our own agency in altering its future trajectory. Our learning and introspection were developed over multiple sessions in the 2019-2020 academic year when the authors participated in a Medical Ethics Forum Fellowship.The Medical Ethics Forum Fellowship (the Forum) of the Medical University of South Carolina (MUSC) is composed of a diverse group of interdisciplinary faculty members, students, and practicing health professionals. The precise membership of the group changes every year, with a number of members continuing for multiple years. Each academic year the Forum focuses on a specific bioethical issue of current interest. Our focus for the academic year 2019-2020 was race and ethnicity in 21st century health care. This paper is the result of our year-long deliberations based on study of the relevant literature, monthly discussions, as well as personal presentations and discussions with nationally known scholars in this field.

Top Ten Tips Palliative Care Clinicians Should Know About Teaching Trainees How to Conduct a Family Meeting.

The family meeting is an essential component of effective palliative care (PC); however, medical students and junior doctors-in-training often consider leading a family meeting to be a daunting task. The old "see one, do one, teach one" axiom should not apply in preparing trainees to conduct a family meeting. After a review of the literature on established PC curricula, trainee perceptions of their PC educational experiences, and documented educational interventions in preparing trainees to conduct a family meeting, we have compiled a list of 10 tips for clinical educators to consider in assisting their students to feel better equipped to conduct productive family meetings.

Life, Love, Hope, Faith, and Death-Too Complex for Likert.

More research to examine factors contributing to health-care disparities at the end of life is greatly needed. This article outlines a failed attempt to quantify some of the motivators in medical decision-making for African American families faced with a decision to pursue or forego a percutaneous endoscopic gastrostomy in a loved one at the end of life. It explores the complexities of spirituality, history, culture, and death in our patient population in Charleston, South Carolina, where health-care disparities are well-documented, and distrust has deep historical roots. It outlines the need for qualitative research, where the defining role of the researcher is to practice the paramount palliative skill of listening.

Nebulized Fentanyl for Dyspnea: A Retrospective Chart Review.

Nebulized fentanyl is well established for analgesia but its use for dyspnea requires further investigation. The aim of our study was to determine the effectiveness of nebulized fentanyl in treating patients with dyspnea and to determine if there were harmful side effects described by patients or their providers. We used a convenience sample of patients from July 1 2014 to July 1 2018 and performed a retrospective chart review. We found that 360 doses of nebulized fentanyl were given to 73 patients during that time period. Of the 73 patients evaluated, 32 patients (43.8%) were female and forty-one were male (56.1%). The median age was 67 and the median length of stay was 9 days. There were no documented findings of bronchospasm, hypotension, or allergic reaction in any of the medical records reviewed. Patients treated with nebulized fentanyl for dyspnea showed a mean decreased respiratory rate of 4.3 breaths/min and a mean increased oxygen saturation of 2.3%. Also, 71% of patients with documented responses experienced an improvement in their dyspnea. Our preliminary data suggest that nebulized fentanyl has limited side effects and may have a role in the treatment of dyspnea. Further research is necessary to determine its efficacy.

Ethical and Clinical Considerations in Treating Infections at the End of Life.

Patients often affirm the goal to pursue comfort at the end of life, although clinicians may struggle with how best to provide comfort and face the ethical dilemma of treating or allowing a suspected infection to unfold. Treating an infection at the end of life does not allow for uniform improvement in symptoms and more time with family and friends. Additionally, there is potential for burden to the patient or health care system and treatment may occur to the exclusion of other comfort measures. Currently, the practice of providing or forgoing antibiotics at the end of life is variable, and literature supporting best practices can be contradictory. Data to support the use or withholding of treatment have been scant and vary across settings and patient populations. We review common obstacles providers face, prognostication tools that may assist in clinical decision making, the ethical support for withholding therapy, and how to factor in potential burdens of treatment. We propose that nurses, whether at the bedside in an acute care or nursing facility or in the home setting as a member of the interdisciplinary home hospice team, are uniquely qualified to help patients and families navigate this challenging clinical decision.

Palliative Care Leadership.

Palliative care is one of the newer health specialties and continues to mature. While there has been remarkable progression of clinical skills and education, there has been a lack of focus on palliative care interdisciplinary leadership or development of leadership skills. This article highlights the importance of interdisciplinary palliative leadership within the 5 realms of clinical practice, research, education, policy/advocacy, and administration. A definition of leadership is offered and discussion of successful leadership skills is described. A current review of leadership opportunities is provided.

The impact of SPARC on age-related cardiac dysfunction and fibrosis in Drosophila.

Tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen, accompanies cardiac ageing in humans and this is linked to an increased risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable to the study of cardiac ageing as well as collagen deposition; however it is unclear whether collagen accumulates in the ageing Drosophila heart. This work examined collagen deposition and cardiac function in ageing Drosophila, in the context of reduced expression of collagen-interacting protein SPARC (Secreted Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked with fibrosis. Heart function was measured using high frame rate videomicroscopy. Collagen deposition was monitored using a fluorescently-tagged collagen IV reporter (encoded by the Viking gene) and staining of the cardiac collagen, Pericardin. The Drosophila heart accumulated collagen IV and Pericardin as flies aged. Associated with this was a decline in cardiac function. SPARC heterozygous flies lived longer than controls and showed little to no age-related cardiac dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV (Viking) and Pericardin increased similarly. Over-expression of SPARC caused cardiomyopathy and increased Pericardin deposition. The findings demonstrate that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it ages. Although having no gross impact on collagen accumulation, reduced SPARC expression extended Drosophila lifespan and cardiac health span. It is proposed that cardiac fibrosis in humans may develop due to the activation of conserved mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle than gross accumulation of collagen.

Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation.

OBJECTIVE: Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and Drug Administration-required labeling. The purpose of this report was to determine whether freezing methacholine solutions in unit-dose syringes would allow less frequent preparation. DESIGN: Diluent containing 0.5% sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare 11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three milliliters of each dilution was placed into 5-mL polypropylene syringes and immediately frozen. Methacholine concentrations were determined using a validated high-performance liquid chromatography assay after preparation (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were allowed to thaw to room temperature. An additional set of each dilution was stored at room temperature for 24 h after thawing and then analyzed for methacholine. RESULTS: Samples > or = 0.062 mg/mL analyzed immediately after thawing retained > or = 90% of labeled potency for at least 6 months, while the 0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h after thawing lost potency. CONCLUSION: If prepared and stored in unit-dose syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be prepared at 4-month intervals. Once thawed, unused methacholine solutions should be discarded.