Clinical research nurse utilisation and role in the conduct of decentralised clinical trials: a literature review.

Background: The decentralised clinical trial (DCT) model has been popularised given its remote or virtual design, permitting expanded participant enrolment into community settings. Clinical research nurses (CRNs) are specially trained in the management of clinical trials; however, the utilisation of the research nurse role relating to decentralised trial conduct is not well-established. Aims: A literature review was conducted to describe the role of the research nurse in the conduct of DCTs and the current utilisation of this nurse specialty for decentralised trial management. Methods: Use of keywords 'DCT' or 'virtual trial' and 'nursing' were used to identify full-text, peer-reviewed literature in the English language and published within the last 10 years that described the clinical research nursing role. Results: Of the 102 pre-screened articles identified across five databases, 11 articles were eligible for full-text analysis. Thematic groupings of common discussion elements included Variance in Decentralised Clinical Trial Model Implementation, CRN Involvement in Decentralised Trial Conduct and Reporting and Shared Challenges of Decentralised Trial Implementation Affecting the CRN Role. Conclusions: Implications of this literature review include expanded trial sponsor awareness of the support requirements to facilitate research nurse utilisation and optimal decentralised trial conduct.

Ventilator hyperinflation determined by peak airway pressure delivered: A randomized crossover trial.

AIM: The aim of this study was to see if a more sophisticated ventilator hyperinflation protocol might result in more sputum clearance compared to manual hyperinflation. BACKGROUND: Hyperinflation has been used to mobilize lung secretions in mechanically ventilated patients in the intensive care unit setting for almost 50 years. In the past decade, rather than using a bag external to the ventilator circuit to deliver hyperinflation (known as "bagging" or "manual hyperinflation"), a new technique has evolved using existing ventilator circuitry (known as "ventilator hyperinflation"). One conservative ventilator hyperinflation protocol has demonstrated equivalence with manual hyperinflation in sputum clearance. DESIGN: A randomized crossover study. METHOD: Patients received manual hyperinflation and ventilator hyperinflation in two randomly ordered treatments on the same day by the same physiotherapist, using a ventilator hyperinflation protocol involving titration of hyperinflation according to airway pressure. RESULTS: Between 2013 and 2018, 48 patients were enrolled in the study. Physiotherapy treatment using ventilator hyperinflation yielded significantly more wet weight sputum (median 2.84 g, IQR 1.81, 4.22) than treatment using manual hyperinflation (median 1.5 g, IQR 0.73, 2.31, P < .001), without significant differences in secondary measures. CONCLUSIONS: A more sophisticated approach to the titration of the volume delivered using ventilator hyperinflation relative to the airway pressure resulted in greater wet weight sputum cleared during physiotherapy treatment. RELEVANCE TO CLINICAL PRACTICE: The results presented in this paper demonstrate that the application of ventilator hyperinflation using peak airway pressure rather than tidal volume may be superior in facilitating sputum clearance and improved oxygenation without patient harm.

Immunotherapy Administration: Oncology Nursing Society Recommendations
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As the use of immunotherapeutic agents increases in single-agent and multimodality treatment regimens, oncology nurses face the challenge of administering and caring for patients receiving new and unique agents. Oncology Nursing Society clinical staff and clinical nurses collaborated to produce a set of recommendations to educate nurses involved with the monitoring of patients receiving immunotherapy on administration procedures and safe handling of these agents to ensure patient and staff safety and to reduce risk of error. The recommendations are meant to provide clinical nurses with a framework on which to build policies and procedures for administering new treatment modalities.
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Cancer Immunotherapy: An Evidence-Based Overview and Implications for Practice.

BACKGROUND: Significant research progress has been made in immunotherapies since the mid-1990s, and this rapid evolution necessitates evidence-based education on immunotherapies, their pathophysiology, and their toxicities to provide safe, effective care.
. OBJECTIVES: The aim of this article is to provide an evidence-based overview, with implications for practice, of checkpoint inhibitors, monoclonal antibodies, oncolytic viral therapies, and chimeric antigen receptor T-cell therapies.
. METHODS: Each immunotherapy category is presented according to the pathophysiology of its immune modulation, the classes of agents within each category, evidence-based toxicities associated with each class, and implications for practice.
. FINDINGS: Immunotherapies vary in their pathophysiology and offer potential to be highly effective for the management of a wide array of cancer types. Understanding the unique pathophysiology and toxicities is necessary to assess, manage, and provide safe, effective patient-focused care.

The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia.

BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04). CONCLUSIONS: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society.

Utility of the Enzyme-Linked Immunospot Interferon-γ-Release Assay to Predict the Risk of Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients.

The ability to distinguish allogeneic hematopoietic cell transplant (allo-HCT) recipients at risk for cytomegalovirus (CMV) reactivation from those who are not is central for optimal CMV management strategies. Interferon γ (IFN-γ) produced by CMV-challenged T cells may serve as an immune marker differentiating these 2 populations. We prospectively monitored 63 CMV-seropositive allo-HCT recipients with a CMV-specific enzyme-linked immunospot (ELISPOT) assay and for CMV infection from the period before transplantation to day 100 after transplantation. Assay results above certain thresholds (50 spots per 250 000 cells for immediate early 1 or 100 spots per 250 000 cells for phosphoprotein 65) identified patients who were protected against CMV infection as long as they had no graft-versus-host disease and/or were not receiving systemic corticosteroids. Based on the multivariable Cox proportional hazards regression model, the only significant factor for preventing CMV reactivation was a CMV-specific ELISPOT response above the determined thresholds (adjusted hazard ratio, 0.21; 95% confidence interval, .05-.97; P = .046). Use of this assay as an additional tool for managing allo-HCT recipients at risk for CMV reactivation needs further validation in future studies. Application of this new approach may reduce the duration and intensity of CMV monitoring and the duration of prophylaxis or treatment with antiviral agents in those who have achieved CMV-specific immune reconstitution.

Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis.

Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.

Influenza vaccination in patients with cancer: factors associated with vaccination practices for patients and their household members.

Presented in part: IDWeek 2014; Philadelphia, PA; October 8-12, 2014 (Poster 1120).

How do Australian ICU survivors fare functionally 6 months after admission?

OBJECTIVES: To determine the extent to which physical function is restored 6 months after intensive care unit admission, and whether this is associated with short or long ICU length of stay (LOS). DESIGN, SETTING AND PARTICIPANTS: We conducted a prospective observational study between April and June 2010. All patients admitted for more than 48 hours to the general ICU at Sir Charles Gairdner Hospital, Perth, Western Australia, were eligible for inclusion. "Short" and "long" ICU LOS were defined as < 8 days and ≥ 8 days, respectively. Six months after ICU admission, an investigator (blinded to baseline data) contacted participants by telephone to administer a follow-up questionnaire based on the Functional Independence Measure (FIM). OUTCOME MEASURES: The primary measure was FIM score; secondary measures were rehabilitation requirement, readmission rate, and whether or not patients had returned to work and driving. RESULTS: 77 patients consented to take part in the study, and 71 were followed up. Median total FIM score (124) and motor (89) and cognitive (35) subscores suggested high-level functional independence at follow-up. Fifty per cent of patients who were workers at baseline had returned to work, and 76% of drivers had returned to driving at follow-up. Paired t tests of the changes in total FIM and its subscales showed that only the motor subscore showed a significant deterioration (mean change, -3.7; P=0.04). Changes for the total FIM did not appear to be correlated with any demographic or baseline data. Furthermore, there appeared to be no difference in FIM between patients with short or long ICU LOS. CONCLUSIONS: Our study showed that patients who survive treatment for life-threatening illness in an Australian ICU for more than 48 hours and are subsequently able to communicate are likely to return to their premorbid functional level (as defined by FIM score) within 6 months.