Nurturing a Spirit of Inquiry: Fundamentals of Evidence-Based Practice in Nursing.

Implementing evidence-based practice in nursing is essential for connecting theoretical knowledge with practical patient care. The spirit of inquiry serves as the foundational step in the evidence-based practice process. Nephrology nurses are positioned to improve patient and system outcomes through an evidence-based practice process, highlighting its transformative impact on nursing practice and patient care. This article provides an overview of evidence-based practice and explores the essential elements for the development of a spirit of inquiry.

Real-World Efficacy and Safety of PARP Inhibitors in Recurrent Ovarian Cancer Patients With Somatic BRCA and Other Homologous Recombination Gene Mutations.

BACKGROUND: Real-world data regarding the use of poly (ADP-ribose) polymerase (PARP) inhibitors in recurrent ovarian cancer patients with non-BRCA homologous recombination (HR) mutations or somatic BRCA mutations are lacking. OBJECTIVE: The purpose of our study is to evaluate the response rate, duration of treatment, time to progression (TTP), and toxicities of olaparib, niraparib, and rucaparib in somatic BRCAm and non-BRCA HR-mutated patients. METHODS: This was a retrospective study using the electronic medical record to identify patients across our health system who were initiated on a PARP inhibitor for ovarian cancer between December 2014 and December 2019. Patients were screened for the presence of a somatic BRCA1/2 mutation or a mutation in non-BRCA HR genes. Data were collected via chart review. RESULTS: For the efficacy analysis, 8 patients had somatic BRCA mutations and 12 patients had HR mutations. The overall response rate (ORR) was 50% for BRCA-mutated (BRCAm) patients and 9.1% for non-BRCA HR-mutated (non-BRCA HRm) patients. 72.7% of patients with non-BRCA HR mutations had stable disease. The duration of therapy ranged from 2 to 66 months. The median TTP was 9.5 months. Overall, 66.7% of patients in the entire cohort started on a reduced dose of PARP inhibitor. Dose reductions due to AEs were observed in 52.4% of patients, while AEs requiring treatment interruption occurred in 61.9%. CONCLUSION AND RELEVANCE: We found that PARP inhibitors provided stable disease in a high proportion of recurrent ovarian cancer patients who had pathogenic HR mutations, with toxicities comparable to major trials. Patients with non-BRCA HR and somatic BRCA mutations could benefit from PARP inhibitors.

Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021.

Importance: Advances in treatment of metastatic breast cancer (MBC) led to changes in clinical practice and treatment costs in the US over the past decade. There is limited information on current MBC treatment sequences and associated costs by MBC subtype in the US. Objectives: To identify treatment patterns by MBC subtype and associated anticancer and supportive drug costs from health care sector and Medicare perspectives. Design, Setting, and Participants: This economic evaluation analyzed data of patients with MBC obtained from the nationwide Flatiron Health database, an electronic health record-derived, deidentified database with data from community and academic practices across the US from 2011 to 2021. Participants included women aged at least 18 years diagnosed with MBC, who had at least 6 months of follow-up data, known hormone receptor (HR) and human epidermal growth factor receptor 2 (ERBB2) receptor status, and at least 1 documented line of therapy. Patients with documented receipt of clinical study drugs were excluded. Data were analyzed from June 2021 to May 2022. Main Outcomes and Measures: Outcomes of interest were frequency of different drug regimens received as a line of therapy by subtype for the first 5 lines and mean medical costs of documented anticancer treatment and supportive care drugs per patient by MBC subtype and years since metastatic diagnosis, indexed to 2021 US dollars. Results: Among 15 215 patients (10 171 patients [66.85%] with HR-positive and ERBB2-negative MBC; 2785 patients [18.30%] with HR-positive and ERBB2-positive MBC; 802 patients [5.27%] with HR-negative and ERBB2-positive MBC; 1457 patients [9.58%] with triple-negative breast cancer [TNBC]) who met eligibility criteria, 1777 (11.68%) were African American, 363 (2.39%) were Asian, and 9800 (64.41%) were White; the median (range) age was 64 (21-84) years. The mean total per-patient treatment and supportive care drug cost using publicly available Medicare prices was $334 812 for patients with HR-positive and ERBB2-positive MBC, $284 609 for patients with HR-negative and ERBB2-positive MBC, $104 774 for patients with HR-positive and ERBB2-negative MBC, and $54 355 for patients with TNBC. From 2011 to 2019 (most recent complete year 1 data are for patients diagnosed in 2019), annual costs in year 1 increased from $12 986 to $80 563 for ERBB2-negative and HR-positive MBC, $99 997 to $156 712 for ERBB2-positive and HR-positive MBC, and $31 397 to $53 775 for TNBC. Conclusions and Relevance: This economic evaluation found that drug costs related to MBC treatment increased between 2011 and 2021 and differed by tumor subtype. These findings suggest the growing financial burden of MBC treatment in the US and highlights the importance of performing more accurate cost-effectiveness analysis of novel adjuvant therapies that aim to reduce metastatic recurrence rates for early-stage breast cancer.

Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions.

The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Paclitaxel pre-medication: A comparison of two steroid pre-medication protocols.

Purpose To evaluate and compare the rate of hypersensitivity reactions between two low-dose steroid pre-medication regimens for paclitaxel-based treatments. Methods This was a single-center, retrospective, descriptive study, comparing the incidence of hypersensitivity reactions in two different dexamethasone pre-medication regimens that took place between July 2013 to December 2014. Patients who were paclitaxel-naïve with a diagnosis of breast or gynecological cancers were included. Patients in the early termination protocol were pre-medicated with a standard pre-medication regimen and if tolerated with no hypersensitivity reaction occurrence, all pre-medications were discontinued after the first two infusions. Patients in the low-dose steroid continuation protocol were pre-medicated with lower doses of dexamethasone, and if the infusion was tolerated with no hypersensitivity reaction, dexamethasone doses were further reduced after the first two infusions. Results A total of 120 patients were included for data analysis. The hypersensitivity reaction rate in the early termination protocol group was 7% (4 out of 60 patients). The hypersensitivity reaction rate in the low-dose continuation protocol group was 5% (3 out of 60 patients). All hypersensitivity reactions occurred during the first infusion, with no hypersensitivity reactions occurring once the dexamethasone pre-medications were discontinued or dose-reduced. All of the patients who experienced a hypersensitivity reaction were successfully re-challenged with paclitaxel and were able to continue their therapy uninterrupted. Conclusion Discontinuing dexamethasone pre-medication altogether after two uneventful infusions or decreasing the dose of dexamethasone paclitaxel pre-medication are both safe alternatives to high-dose steroid pre-medications recommended in product labeling.

T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab.

Purpose Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.

Evaluation guidelines for adult and pediatric kidney transplant programs: the Missouri experience.

CONTEXT: Rigorous candidate evaluation is paramount for estimating risk and long-term success with transplantation. In addition, because of increasing waiting times, patients are seeking listing at multiple centers or transferring waiting time from one center to another. Variations in center evaluation criteria are becoming increasingly important to patients. OBJECTIVE: To describe the similarities and differences among the evaluation guidelines for adult and pediatric kidney transplant programs in Missouri. DESIGN: A descriptive design was used. SETTING AND PARTICIPANTS: Kidney transplant nurse coordinators from 7 adult and 4 pediatric kidney transplant programs from 10 centers in Missouri were invited to submit the kidney transplant candidate evaluation guidelines from their programs. RESULTS: Guidelines were submitted by nurse coordinators from all programs. Consults with the kidney transplant team members, including surgeon, nephrologist, social worker, and nurse coordinator, were included in all of the programs. For the adult programs, 67% (20/30) of the tests and laboratory values were agreed on by at least 70% of the program transplant team members. Similarly, for the pediatric programs, 62% (16/26) of the age-appropriate tests and laboratory values were agreed on by at least 75% of the program transplant team members. CONCLUSIONS: Within the Missouri programs, testing is consistent whether the center is large or small, adult or pediatric. Transplant teams should periodically review their kidney transplant recipient evaluation criteria for similarities to and differences from the current state-of-the-science and surrounding programs.