Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. RESULTS: Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. CONCLUSION: Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Successful Pancreatic Cancer Screening Among Individuals at Elevated Risk Using Endoscopic Ultrasound and Magnetic Resonance Imaging: A Community Hospital Experience.

OBJECTIVES: Guidelines for testing individuals at risk (IAR) for developing pancreatic duct adenocarcinoma (PC) are being advanced from university hospital populations. We implemented a screen-in criteria and protocol for IAR for PC in our community hospital setting. METHODS: Eligibility was based on germline status and/or family history of PC. Longitudinal testing continued, alternating between endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI). The primary objective was to analyze pancreatic conditions and their associations with risk factors. The secondary objective was to evaluate the outcomes and complications resulting from testing. RESULTS: Over 93 months, 102 individuals completed baseline EUS, and 26 (25%) met defined endpoints of any abnormal findings in the pancreas. Average enrollment was 40 months, and all participants with endpoints continued standard surveillance. Two participants (1.8%) had endpoint findings requiring surgery for premalignant lesions. Increasing age predicted for endpoint findings. Analysis of longitudinal testing suggested reliability between the EUS and MRI results. CONCLUSIONS: In our community hospital population, baseline EUS was effective in identifying the majority of findings; advancing age correlated with a greater chance of abnormalities. No differences were observed between EUS and MRI findings. Screening programs for PC among IAR can be successfully performed in the community setting.

Post-severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Treatment Hospitalizations as a Sentinel for Emergence of Viral Variants in New York City.

We partnered with the US Department of Health and Human Services to treat high-risk, nonadmitted coronavirus disease 2019 (COVID-19) patients with bamlanivimab in the Bronx, New York per Emergency Use Authorization criteria. Increasing posttreatment hospitalizations were observed monthly between December 2020 and March 2021 in parallel to the emergence of severe acute respiratory syndrome coronavirus 2 variants in New York City.

Everyone is Someone's Child: The Experiences of Pediatric Nurses Caring for Adult COVID-19 Patients.

PURPOSE: During the COVID-19 pandemic, pediatric nurses at one medical center in New York assumed care of COVID-19 adult patients. The purpose of this study was to understand pediatric nurses' experiences during the peak of the COVID-19 pandemic, when they were caring for patients outside of their usual practice. DESIGN AND METHODS: A qualitative descriptive study was implemented, and a descriptive survey was sent to all pediatric nurses who worked during the peak of the pandemic, from March 2020 - May 2020. Categorical responses were analyzed using descriptive statistics and free texts were coded to develop central themes. RESULTS: Four themes emerged from the data: concerns for safety, unprepared to care, nurses' emotional responses, and persevering together. CONCLUSIONS: As pediatric nurses adjusted to caring for a new disease and a new population of patients, concerns of safety and preparedness emanated. The need for teamwork and support was emphasized by nurses. The impact that nurses' experiences had on their emotional wellbeing was also highlighted. PRACTICE IMPLICATIONS: Exploring pediatric nurses' experiences during a pandemic is important, as it furthers understanding and guides efforts to enhance preparedness for a future pandemic or public health emergency. Findings from this study illustrate the need to provide nurses with support for both their physical and emotional health.

Oncology nursing support for safe and effective use of eribulin in metastatic breast cancer.

Nurse practitioners play important roles in breast cancer prevention, early detection, therapeutic efficacy, and surveillance. Assessment of a patient's health status is part of the nine nurse practitioner core competencies updated in 2012 by the National Organization of Nurse Practitioner Faculties. Although adverse events are common in treatment for metastatic breast cancer (MBC), proactive management strategies can limit the number and/or severity of adverse events. Additionally, knowledge of common metastatic sites and clinical signs/symptoms of recurrence provides one of the first-line strategies for successful treatment. We review five case studies of women with MBC who were managed successfully with eribulin mesylate in late lines of therapy after at least two chemotherapeutic regimens for advanced breast cancer that included both an anthracycline and a taxane in either the adjuvant or metastatic setting.

The effectiveness of delegation interventions by the registered nurse to the unlicensed assistive personnel and their impact on quality of care, patient satisfaction, and RN staff satisfaction: a systematic review.

BACKGROUND: Delegation by the registered nurse is a decision making process that includes assessment, planning, implementation, and evaluation. Due to an ever-expanding global shortage of nurses, registered nurses are increasingly dependent on unlicensed assistive personnel to assist in the provision of safe patient care. Delegation is recognised as a fundamental nursing skill that can be utilised effectively to improve quality care. OBJECTIVE: To examine and synthesize the best available evidence regarding the impact of delegation interventions used by the registered nurse with the unlicensed assistive personnel and their impact on quality of care, patient satisfaction, and registered nurse staff satisfaction. INCLUSION CRITERIA: Registered nurses and unlicensed assistive personnel in patient care settings where delegation occurs.This review considered studies that evaluated the effectiveness of delegation interventions by registered nurses to unlicensed assistive personnel.The outcomes examined were quality of care, patient satisfaction, and/or registered nurse staff satisfaction as measured by validated and reliable tools.The review first considered randomised controlled trials; in their absence other research designs, such as non-randomised controlled trials, or other quasi-experimental studies, observational studies and descriptive studies were considered for inclusion in the systematic review. SEARCH STRATEGY: The search strategy aimed to find both published and unpublished studies in the English language from the inception of the included databases through December 2011. The databases searched included the Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL, Healthsource Nursing/Academic edition, and PsycINFO. A search of the grey literature and electronic hand searching of relevant journals was also performed. METHODOLOGICAL QUALITY: The studies selected for retrieval were critically evaluated by two independent reviewers for methodological quality using standardised critical appraisal instruments from the Joanna Briggs Institute. DATA COLLECTION: Data were extracted using standardised data extraction instruments from the Joanna Briggs Institute. DATA SYNTHESIS: Studies were found to have significant heterogeneity between the populations and interventions of the included studies; therefore, pooled statistical meta-analysis could not be completed. The findings are presented in narrative form. RESULTS: Two quasi-experimental studies were identified. In one study, the women counselled by the lay nurse aides received 80% of recommended messages compared to 75% received by the women counselled by the nurse-midwives (ß= 4.7, 95%CI: -1.7, 11.0; Non-inferiority). Non-inferiority was demonstrated between the lay nurse aides and the nurse-midwives with respect to communication techniques. The mean performance was high, 95% and 98% among nurse-midwives and lay nurse aides respectively (ß =2.4, 95%CI: -0.2, 5.0; Non-inferiority). No difference was found between the nurse-midwives and the lay nurse aides in providing antenatal counselling, education, and maternal-newborn care when proper training and supervision was given. The other study examined six hypotheses that looked at quality of care outcomes in a care model where the registered nurse delegated tasks to unlicensed assistive personal. Five of these outcomes showed no significant improvement as a result of the intervention. Patient knowledge about intravenous therapy was the only quality of care outcome that showed improvement post-intervention with scores increasing from 27% at baseline to 78% at 12 months. There was no improvement in the one hypotheses evaluating registered nurses job satisfaction. CONCLUSIONS: There is a paucity of evidence on the effectiveness of delegation interventions and strategies by registered nurses to unlicensed assistive personnel. Delegation interventions require characteristics such as teamwork, training, support, supervision, communication, and evaluation to positively impact quality of care, patient satisfaction, and registered nurse staff satisfaction outcomes. IMPLICATIONS FOR PRACTICE: Task shifting could have a positive impact on quality of care and staff satisfaction while providing the registered nurse with an opportunity to increase efficiency. IMPLICATIONS FOR RESEARCH: The areas of feedback and evaluation in the registered nurse / unlicensed assistive personnel relationship needs further study.

Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer.

PURPOSE: Tipifarnib is a farnesyl transferase (FTase) inhibitor that has activity in metastatic breast cancer and enhances the efficacy of cytotoxic agents in preclinical models. We evaluated the biological effects of tipifarnib in primary breast cancers in vivo, whether adding tipifarnib to preoperative chemotherapy increased the pathologic complete response rate (pCR) at surgery, and determined whether biomarkers predictive of pCR could be identified. EXPERIMENTAL DESIGN: Forty-four patients with stage IIB-IIIC breast cancer received up to four cycles of neoadjuvant doxorubicin-cyclophosphamide (AC) every 2 weeks plus tipifarnib and filgrastim followed by surgery. Enzymatic assays measuring FTase activity and Western blotting for phospho (p)-signal transducer and activator of transcription 3 (STAT3), phospho-extracellular signal-regulated kinase, p-AKT, and p27 were done in 11 patients who agreed to optional tissue biopsies before therapy and 2 hours after the final dose of tipifarnib during the first cycle, and predictive biomarkers were evaluated by immunohistochemistry in 33 patients. The trial was powered to detect an improvement in breast pCR rate of 10% or less expected for AC alone to 25% for AC-tipifarnib (alpha = 0.05, beta = 0.10). RESULTS: Eleven patients had a breast pCR (25%; 95% confidence interval, 13-40%). FTase enzyme activity decreased in all patients (median, 91%; range, 24-100%) and p-STAT3 expression decreased in 7 of 9 (77%) patients. Low tumor Ki-67 expression (below the median of 60%) at baseline was significantly associated with resistance to therapy (P = 0.01). CONCLUSION: Tipifarnib inhibits FTase activity in human breast tumors in vivo, is associated with down-regulation of p-STAT3, and enhances the breast pCR rate, thus meriting further evaluation.

A phase I trial of gemcitabine administered as a 96-h continuous intravenous infusion in patients with advanced carcinoma and lymphoma.

BACKGROUND AND OBJECTIVE: Preclinical data suggest gemcitabine may have schedule-dependent activity favoring prolonged infusion. We sought to determine the recommended phase II dose (RPTD) and toxicity of gemcitabine when given as a continuous intravenous (CIVI) over 96 h. PATIENTS AND METHODS: Gemcitabine was initially given at 1 mg/m(2)/d for 48, then 72, and finally 96 h. The dose was then increased to 2, 4, 6, 10, 15, 20, and 25 mg/m(2)/d. Dose levels of 7, 8, 9 mg/m(2)/d as 96-h infusion were added later after a protocol modification. After identifying the RPTD using an every 3-wk schedule, we then evaluated the feasibility of repeating the infusion every 2 wk, and then weekly for 3 of 4 wk. RESULTS: Thirty-four patients with a variety of tumor types received a total of 126 cycles of therapy (median of 2 cycles, range 1-10 cycles). The RPTD was 8 mg/m(2)/d every 3 wk, and 6 mg/m(2)/d every 2 wk. The most common grade 2 or higher toxicities at all dose levels (>or= grade 2) included fever (n = 14), dyspnea (n = 7), mucositis (n = 6), hypotension (n = 6), nausea/vomiting (n = 6), and fatigue (n = 5). Neutropenia and/or thrombocytopenia were uncommon. CONCLUSION: Administration of gemcitabine as a 96-h infusion results in a markedly different toxicity profile and RPTD than when given by a conventional 30-min infusion. The RPTD was 8 mg/m(2)/d (32 mg/m(2)/course) when given every 3 wk, or 6 mg/m(2)/d (24 mg/m(2)/course) when given every 2 wk.

Targeted inhibition of farnesyltransferase in locally advanced breast cancer: a phase I and II trial of tipifarnib plus dose-dense doxorubicin and cyclophosphamide.

PURPOSE: To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo. PATIENTS AND METHODS: Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination. RESULTS: When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib. CONCLUSION: Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC.

Phase II study of weekly docetaxel alone or in combination with trastuzumab in patients with metastatic breast cancer.

This study was designed to determine the efficacy and toxicity of weekly docetaxel in metastatic breast cancer when given alone (for HER2/neu negative disease) or with trastuzumab (for HER2/neu overexpressing disease). Patients with metastatic breast carcinoma received docetaxel given on 2 different schedules (group 1A, 33 mg/m2 weekly [n = 21]; group 1B, 40 mg/m2 weekly for 3 weeks with 1 week off [n = 14]). Patients with HER2/neu overexpressing disease also received trastuzumab 4 mg/kg on day 1, then 2 mg/kg on days 8 and 15 of each 28-day cycle (group 2). Fifty-two patients were treated with docetaxel alone (group 1A/B, n = 35) or in combination with trastuzumab (group 2, n = 17). Prior taxane therapy given every 3 weeks had been used for metastatic disease in 19 of 35 patients (54%) in group 1A/B and in 2 of 17 patients (12%) in group 2. The mean delivered dose intensity of docetaxel was 29 mg/m2 per week. Partial response occurred in 7 of 35 patients (21%; 95% exact binomial confidence interval [CI], 9%-38%) treated with docetaxel alone, including 3 of 19 taxane-pretreated patients (16%) and 4 of 16 taxane-naive patients (25%). Partial response occurred in 10 of 17 patients (59%; 95% CI, 34%-82%) treated with docetaxel/trastuzumab. The most common grade 3/4 toxicities, occurring in more than or equal to 10% of patients, included neutropenia (21%), pulmonary toxicity (12%), and hyperglycemia (10%). The median times to disease progression were 4.5 months (95% CI, 2.5-6.5 months) in the docetaxel group and 8.5 months (95% CI, 4.5-12.5 months) in the docetaxel/trastuzumab group. Weekly docetaxel/trastuzumab is an effective regimen for patients with HER2/neu overexpressing metastatic breast cancer. Weekly docetaxel may be effective in as many as 20% of patients who had progressive disease after treatment with taxanes given every 3 weeks.

Phase II trial of infusional cyclophosphamide, idarubicin, and etoposide in poor prognosis non-Hodgkin's lymphoma.

The purpose of this study was to determine the complete response (CR) rate, failure-free survival (FFS), and overall survival (OS) of patients with poor-prognosis intermediate-grade non-Hodgkin's lymphoma (NHL) after treatment with cyclophosphamide, idarubicin, and etoposide given as a continuous intravenous infusion (CIVI) over 96 hours (infusional CIE), including patients with relapsed/refractory disease and patients with no prior therapy but at least two poor-risk features by the age-adjusted International Prognostic Index. Forty-two patients with previously untreated NHL (N = 24) or relapsed/refractory (N = 18) NHL received cyclophosphamide (200 mg/m2/d), idarubicin (2.5-3.0 mg/m2/d) and etoposide (60 mg/m2/d) given by a 96-hour CIVI every 3 weeks for a maximum of 8 cycles. All patients also received granulocyte-colony-stimulating factor. CR occurred in 10 of 24 patients (42%; 95% confidence intervals [CI] 22%, 62%) treated with CIE as first-line therapy, and in 3 of 18 patients (17%; 95% CI 20%, 32%) treated with CIE as second-line or greater therapy. One-year FFS and OS were 42% and 64%, respectively, in patients with no prior therapy, and 17% and 56% in patients with prior therapy. Severe (grade III) or life-threatening (grade IV) toxicity included leukopenia (59%), anemia (61%), thrombocytopenia (31%), and infection (10%). Two patients (4%) died due to treatment related infectious complications. It is unlikely that infusional CIE produces a CR rate more than about 60% in poor-risk patients with intermediate-grade NHL when used as first-line therapy, or more than about 30% in patients receiving the regimen as second-line therapy. Substitution of idarubicin for doxorubicin in this setting, therefore, is not associated with an improved response rate.

Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies.

The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m(2) as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43%) patients treated with irinotecan 300 mg/m(2) and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m(2), and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11% of all courses), fatigue (3.4%) and hand-foot syndrome (3.4%). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m(2) and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.