Novel Enhanced Recovery After Surgery Pathway Reduces Length of Stay and Postoperative Opioid Usage in Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion.

PURPOSE: The goal of this study was to compare our institution's recently implemented enhanced recovery after surgery (ERAS) protocol to previous post-operative management for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion, specifically assessing length of stay, opioid consumption, and pain scores. METHODS: This is a retrospective analysis that compares the length of stay, opioid consumption, and pain scores of patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis. Patients were analyzed prior to the implementation of our ERAS protocol, deemed the traditional pain pathway (TPP), to those who underwent the ERAS pathway. All patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis were included. Patients were excluded if they weighed less than 40kg, had significant comorbidities, or had non-idiopathic causes of scoliosis. RESULTS: We examined 22 patients in the TPP cohort and 20 in the ERAS cohort. Length of stay in the ERAS cohort was significantly reduced compared to the TPP by 1.7 days (P<0.01). Overall opioid consumption was also significantly reduced in the ERAS with 1.4 ± 0.7 morphine equivalents (ME)/kg compared to the TPP 2.4 ± 1.1 ME/kg (P < 0.01). We found no difference in pain scores between the two groups. CONCLUSION: Implementation of an ERAS pathway at our institution significantly reduced length of stay and opioid consumption in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion. These outcomes reduce morbidity and costs associated with posterior spinal fusion and provide an overall improvement in the quality of care for our patients.

Procedural Pain Management: Clinical Practice Recommendations.

Undergoing potentially painful procedures is necessary among patients of all ages. Nurses are responsible to optimize safety and minimize harm for patients. The American Society for Pain Management Nursing (ASPMN) holds the position that all patients undergoing painful procedures have the right to safe and effective pain management throughout the phases of care, and that the interprofessional healthcare team ensures such ethical obligation is fulfilled within a framework of the patients or their designees' goals and preferences. From that position, all nurses, clinicians, and health care organizations are strongly encouraged to offer multimodal pain management that includes integrative interventions when managing procedure related pain.

Procedural Pain Management: Clinical Practice Recommendations American Society for Pain Management Nursing.

Throughout the life span procedures are common within health care and have the potential to cause pain. Nurses have an ethical responsibility involving the care of people with pain. The American Society for Pain Management Nursing holds the position that all patients undergoing painful procedures have the right to safe and effective pain management throughout the phases of care and that the interprofessional health care team ensures such ethical obligation is fulfilled within a framework of patients or their designees' goals and preferences. It is recommended that nurses, other health care providers, and health care organizations offer the use of integrative intervention for managing pain during procedures.

Development and evaluation of a teaching and learning approach in cross-cultural care and antidiscrimination in university nursing students.

BACKGROUND: Cross-cultural care and antidiscrimination are vital to ethical effective health systems. Nurses require quality educational preparation in cross-cultural care and antidiscrimination. Limited evidence-based research is available to guide teachers. OBJECTIVES: To develop, implement and evaluate an evidence-based teaching and learning approach in cross-cultural care and antidiscrimination for undergraduate nursing students. DESIGN: A quantitative design using pre- and post-survey measures was used to evaluate the teaching and learning approach. SETTINGS: The Bachelor of Nursing program in an Australian university. PARTICIPANTS: Academics and second year undergraduate nursing students. METHODS: A literature review and consultation with academics informed the development of the teaching and learning approach. Thirty-three students completed a survey at pre-measures and following participation in the teaching and learning approach at post-measures about their confidence to practice cross-cultural nursing (Transcultural Self-efficacy Tool) and about their discriminatory attitudes (Quick Discrimination Index). RESULTS: The literature review found that educational approaches that solely focus on culture might not be sufficient in addressing discrimination and racism. During consultation, academics emphasised the importance of situating cross-cultural nursing and antidiscrimination as social determinants of health. Therefore, cross-cultural nursing was contextualised within primary health care and emphasised care for culturally diverse communities. Survey findings supported the effectiveness of this strategy in promoting students' confidence regarding knowledge about cross-cultural nursing. There was no reported change in discriminatory attitudes. The teaching and learning approach was modified to include stronger experiential learning and role playing. CONCLUSIONS: Nursing education should emphasise cross-cultural nursing and antidiscrimination. The study describes an evaluated teaching and learning approach and demonstrates how evaluation research can be used to develop cross-cultural nursing education interventions.

Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency.

X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine receptor γ chain. These mutations classically lead to complete absence of functional T and natural killer cell lineages as well as to intrinsically compromised B cell function. Although human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation (HSCT) is highly successful in SCID-X1 patients, HLA-mismatched procedures can be associated with prolonged immunodeficiency, graft-versus-host disease, and increased overall mortality. Here, 10 children were treated with autologous CD34(+) hematopoietic stem and progenitor cells transduced with a conventional gammaretroviral vector. The patients did not receive myelosuppressive conditioning and were monitored for immunological recovery after cell infusion. All patients were alive after a median follow-up of 80 months (range, 54 to 107 months), and a functional polyclonal T cell repertoire was restored in all patients. Humoral immunity only partially recovered but was sufficient in some patients to allow for withdrawal of immunoglobulin replacement; however, three patients developed antibiotic-responsive acute pulmonary infection after discontinuation of antibiotic prophylaxis and/or immunoglobulin replacement. One patient developed acute T cell acute lymphoblastic leukemia because of up-regulated expression of the proto-oncogene LMO-2 from insertional mutagenesis, but maintained a polyclonal T cell repertoire through chemotherapy and entered remission. Therefore, gene therapy for SCID-X1 without myelosuppressive conditioning effectively restored T cell immunity and was associated with high survival rates for up to 9 years. Further studies using vectors designed to limit mutagenesis and strategies to enhance B cell reconstitution are warranted to define the role of this treatment modality alongside conventional HSCT for SCID-X1.

Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction.

Genetic defects in the purine salvage enzyme adenosine deaminase (ADA) lead to severe combined immunodeficiency (SCID) with profound depletion of T, B, and natural killer cell lineages. Human leukocyte antigen-matched allogeneic hematopoietic stem cell transplantation (HSCT) offers a successful treatment option. However, individuals who lack a matched donor must receive mismatched transplants, which are associated with considerable morbidity and mortality. Enzyme replacement therapy (ERT) for ADA-SCID is available, but the associated suboptimal correction of immunological defects leaves patients susceptible to infection. Here, six children were treated with autologous CD34-positive hematopoietic bone marrow stem and progenitor cells transduced with a conventional gammaretroviral vector encoding the human ADA gene. All patients stopped ERT and received mild chemotherapy before infusion of gene-modified cells. All patients survived, with a median follow-up of 43 months (range, 24 to 84 months). Four of the six patients recovered immune function as a result of engraftment of gene-corrected cells. In two patients, treatment failed because of disease-specific and technical reasons: Both restarted ERT and remain well. Of the four reconstituted patients, three remained off enzyme replacement. Moreover, three of these four patients discontinued immunoglobulin replacement, and all showed effective metabolic detoxification. All patients remained free of infection, and two cleared problematic persistent cytomegalovirus infection. There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is safe, with effective immunological and metabolic correction, and may offer a viable alternative to conventional unrelated donor HSCT.

Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening.

Severe combined immunodeficiency (SCID) carries a poor prognosis without definitive treatment by hematopoietic stem cell transplantation. The outcome for transplantation varies and is dependent on donor status and the condition of the child at the time of transplantation. Diagnosis at birth may allow for better protection of SCID babies from infection and improve transplantation outcome. In this comparative study conducted at the 2 designated SCID transplantation centers in the United Kingdom, we show that SCID babies diagnosed at birth because of a positive family history have a significantly improved outcome compared with the first presenting family member. The overall improved survival of more than 90% is related to a reduced rate of infection and significantly improved transplantation outcome irrespective of donor choice, conditioning regimen used, and underlying genetic diagnosis. Neonatal screening for SCID would significantly improve the outcome in this otherwise potentially devastating condition.

Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study.

BACKGROUND: Stem-cell transplantation can cure primary immunodeficiencies. However, in patients with pre-existing organ toxicity, patients younger than 1 year, and those with DNA or telomere repair disorders, chemotherapy-based conditioning is poorly tolerated and results in major morbidity and mortality. We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity. METHODS: 16 high-risk patients underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consisting of two rat anti-CD45 monoclonal antibodies YTH 24.5 and YTH 54.12 for myelosuppression, and alemtuzumab (anti-CD52) and fludarabine, and low dose cyclophosphamide for immunosuppression. Donors were matched siblings (n=5), and matched (9) and mismatched (2) unrelated donors. FINDINGS: Antibody-based conditioning was well tolerated, with only two cases of grade 3 and no grade 4 toxicity. Rates of clinically significant acute (n=6, 36%) and chronic graft-versus-host disease (GVHD) (n=5, 31%) were acceptable. 15 of 16 patients (94%) engrafted, of whom 11 (69%) achieved full or high-level mixed chimerism in both lymphoid and myeloid lineages, and three achieved engraftment in the T-lymphoid lineage only. One patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this high-risk cohort were alive and cured from their underlying disease. INTERPRETATION: Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor. FUNDING: None.