How clinical resource nurses can support new nurses and address safety concerns.

ABSTRACT: Inexperienced nursing staff can jeopardize patient safety and contribute to burnout. This quality improvement project evaluated a clinical resource nurse (CRN) role designed to address disparities in nurses' skills and experience. Survey results suggested that the CRN role effectively supported novice nurses.

Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy.

Significant enthusiasm currently exists for new immunotherapeutic strategies: blocking the interaction between programmed death-1 receptor on T-cells and programmed death-ligand 1 on tumor cells to boost immune system stimulation to fight cancer. Immunomodulation with the antiprogrammed death-1/programmed death-ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and extend overall survival from several pivotal phase I/II studies in melanoma, renal cell carcinoma, and non-small cell lung cancer. This has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. We reviewed the clinical efficacy and safety of each compound based upon major registered clinical trials and published clinical data. Overall, response rate of more than 20% is consistently seen across all these trials, with maximal response of approximately 50% achieved by certain single antiprogrammed death-1 agents or when used in combination with cytotoxic T-lymphocyte antigen-4 blockade. The responses seen are early, durable, and have continued after treatment discontinuation. Immune-related adverse events are the most common side effects seen in these clinical trials. Overall, the skin and gastrointestinal tract are the most common organ systems affected by these compounds while hepatic, endocrine, and neurologic events are less frequent. These side effects are low grade, manageable, and typically resolve within a relatively short time frame with a predictable resolution pattern given proper management. We therefore propose detailed guidelines for management of major immune-related adverse events that are anticipated with antiprogrammed death-1/programmed death-ligand 1 therapies based on general experience with other monoclonal antibodies and the established management algorithms for immune-related adverse events for cytotoxic T-lymphocyte antigen-4 blockade with ipilimumab. We anticipate that the antiprogrammed death-1 strategy will become a viable and crucial clinical strategy for cancer therapy.

Early antibiotic discontinuation in patients with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoscopy cultures.

OBJECTIVES: Preliminary data suggest that antibiotic discontinuation in patients with negative quantitative bronchoscopy and symptom resolution will not increase mortality. Because our hospital algorithm for antibiotic discontinuation rules out ventilator-associated pneumonia in the setting of negative quantitative bronchoscopy cultures, we compared antibiotic utilization and mortality in empirically treated, culture-negative ventilator-associated pneumonia patients whose antibiotic discontinuation was early versus late. DESIGN: Retrospective, observational cohort study. SETTING: Eight hundred sixty-seven bed, tertiary care, teaching hospital in Hartford, CT. PATIENTS: Eighty-nine patients with clinically suspected ventilator-associated pneumonia and a negative (<10 colony forming units/mL) quantitative bronchoscopy culture between January 2009 and March 2012. Early discontinuation patients (n = 40) were defined as those who had all antibiotic therapy stopped within one day of final negative culture report, whereas late discontinuation patients (n = 49) had antibiotics stopped later than one day. MEASUREMENTS: Univariate analyses assessed mortality, antibiotic duration, and frequency of superinfections. Multivariate logistic regression was performed to assess the effect of early discontinuation on hospital mortality. RESULTS: Patients had a mean ± SD Acute Physiology and Chronic Health Evaluation II score of 26.0 ± 6.0. Mortality was not different between early discontinuation (25.0%) and late discontinuation (30.6%) patients (p = 0.642). Antibiotic duration (days) was also not different for patients who died vs. those who survived (Median [interquartile range]: 3 [1-7.5] vs. 3 [1.75-6.25], respectively, p = 0.87), and when controlling for baseline characteristics and symptom resolution, only Acute Physiology and Chronic Health Evaluation II score was associated with hospital mortality on multivariate analyses. There were fewer superinfections (22.5% vs. 42.9%, p = 0.008), respiratory superinfections (10.0% vs. 28.6%, p = 0.036), and multidrug resistant superinfections (7.5% vs. 35.7%, p = 0.003), in early discontinuation compared with late discontinuation patients. CONCLUSIONS: In this severely ill population with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoalveolar lavage cultures, early discontinuation of antibiotics did not affect mortality and was associated with a lower frequency of MDR superinfections.

Regression of myelinated retinal nerve fibers in a glaucomatous eye.

PURPOSE: The purpose of this study is to present a case of a patient with primary open angle glaucoma and poorly controlled intraocular pressure, who underwent photodocumented atrophy of myelinated retinal nerve fibers. CASE REPORT: A 48-year-old woman with high myopia, refractive amblyopia, and extensive myelination of retinal nerve fibers underwent profound atrophy and regression of the myelination during an 8-year period. CONCLUSIONS: Myelinated retinal nerve fibers can atrophy and regress because of neurodegenerative conditions such as glaucoma.

Inotuzumab ozogamicin in the treatment of relapsed/refractory acute B cell lymphoblastic leukemia.

The improvement in outcomes of adult patients with acute lymphoblastic leukemia (ALL) has been modest, with the exception of Philadelphia chromosome-positive disease, despite advances in supportive care and stem cell transplantation. The recent approvals of novel agents, including the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and chimeric antigen receptor T-cell products are changing the management of B-ALL, which traditionally relied on chemotherapy-based approaches. Inotuzumab ozogamicin is a humanized CD22 monoclonal antibody linked to the cytotoxic agent calicheamicin. CD22 is expressed on leukemic blasts in >90% of ALL patients, and inotuzumab ozogamicin has shown excellent clinical activity even among heavily pretreated relapsed/refractory (R/R) B-ALL patients and elderly B-ALL patients. Clinical trials have shown superior survival with the drug over chemotherapy-based approaches in the first- or second-line salvage therapy for relapsed B-ALL as monotherapy. Currently, new trials are evaluating inotuzumab ozogamicin in the frontline setting in combination-based approaches. In this review, we summarize the preclinical and clinical data of inotuzumab ozogamicin in R/R B-ALL and foresee the future use of this drug in the clinic.

Plerixafor as a salvage mobilization strategy for haploidentical peripheral blood allogeneic stem cell transplantation.

In allogeneic stem cell mobilization, peripheral blood stem cell mobilization with filgrastim can be considered standard of care. Poor mobilizers may be at risk for inadequate stem cell collection during apheresis. He we present a successful case of salvage plerixafor use with filgrastim in a haploidentical identical transplant patient.