Working with a Statistician on a Data Analysis Plan.

The author describes collaboration between a statistician and nurse or midwife scientist to develop a data analysis plan.

Statistical Methods for Pre-Post Intervention Design.

The author provides an overview of options for statistical tests in pre-post analysis.

The Role of Confounders in Statistical Analysis.

Researchers can limit the effects of study design limitations on research findings through statistical analysis that includes crucial covariates and accounts for confounding.

Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the "fail-and-learn" strategy during the first two waves of the pandemic in 2020.

BACKGROUND: The early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the "emergency use authorization" (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the "fail-and-learn" strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials. METHODS: A retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into "Early 2020" (March 1-June 30) versus "Late 2020" (July 1-December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive vs. non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement. RESULTS: From a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic. The results showed a minimal, yet statistically significant, association with hydroxychloroquine in "Early 2020" and remdesivir in "Late 2020" with reduced odds of mortality (odds ratios 0.72 and 0.76, respectively; P = 0.01). Azithromycin was the only medication associated with decreased odds of mortality during both study time-windows (odds ratios 0.79 and 0.68, respectively; P < 0.01). In contrast, the necessity for oxygen supply showed significantly increased odds of mortality beyond the effect of all investigated medications. Of all the covariates associated with increased mortality, invasive mechanical ventilation had the highest odds ratios of 8.34 in the first surge and 9.46 in in the second surge of the pandemic (P < 0.01). CONCLUSION: This retrospective multicenter observational cohort study on 9,638 hospitalized patients with severe COVID-19 during revealed that the necessity for invasive ventilation had the highest odds of mortality, beyond the variable effects observed by administration of the prevalent EUA-approved investigational drugs during the first two surges of the early 2020 pandemic in the United States.

Nursing opinions on collaborating with residents in new and legacy OB/GYN programs.

Collaboration among physicians and nurses is vital and has shown to lead to better patient care and improve outcomes. Our study surveyed two groups of Labor and Delivery nurses in two regionally similar community hospitals in midwestern United States: one group from a new Obstetrics and Gynecology (OB/GYN) residency program (n = 49) and another from an established (legacy) OB/GYN residency program (n = 49). The survey asked nurses from the hospital with new and legacy residency program about preparedness for working with residents, perceptions of nurse-resident-patient relationships, collaboration and opinions about how resident physicians impact patient safety. Most nurses from the legacy residency program showed positive perceptions of collaboration with the residency and institutional support. In the new OB/GYN residency program, nurses were generally neutral and showed skepticism about collaboration with OB/GYN resident physicians and institutional support. Nurses from both hospitals felt similarly in their comfort escalating issues to administration and in their satisfaction with interprofessional collaboration within Labor and Delivery units. Providing nurses with opportunities to learn about the role of new medical residents in their patient care setting as well as intentional collaboration between nursing and residency program administration might result in more effective collaboration between physician residents and nursing staff.

Assessing Nursing Sentiments on Nurse-Resident Physician Collaboration and Administrative Support in the Labor and Delivery Setting: Development and Validation of a Novel Instrument.

OBJECTIVE: To develop a survey instrument that: 1) investigates the dynamics of collaboration in multidisciplinary care units such as labor and delivery (L&D); and (2) uniquely determines the collaborative relationships between nurses and resident physicians. BACKGROUND: An effective interprofessional collaboration between healthcare providers is considered a critical component in delivering high-quality care to patients and lies at the root of ensuring positive patient outcomes. METHODS: Two samples of responses (n = 98) were collected from L&D nurses working in 2 hospitals: 1 with novel obstetrics and gynecology (OB/GYN) residency program and 1 with legacy OB/GYN residency program. Descriptive statistics and reliability statistics (Cronbach's α and item-total correlations) were calculated for each sample. RESULTS: Reliability analysis revealed strong internal consistency of the survey items in both samples even after completing single-item deletion analysis. CONCLUSIONS: Findings suggest that our 11-item instrument shows promise in effectively assessing nursing sentiments toward collaboration with resident physicians.

A retrospective analysis of bleeding risk with rivaroxaban, enoxaparin, and aspirin following total joint arthroplasty or revision.

STUDY OBJECTIVE: Rivaroxaban, enoxaparin, and aspirin are commonly used medications for thromboprophylaxis following lower extremity joint arthroplasty or revision. Previous research has demonstrated efficacy in preventing venous thromboembolism with each medication, however, the comparative risk of bleeding between them remains poorly understood. The aim of this study was to compare the odds of bleeding between rivaroxaban, enoxaparin, and aspirin following lower extremity joint arthroplasty or revision. DESIGN: This is a 3-year retrospective cohort study. SETTING: Data were obtained from 148 facilities across 55 states and territories of the United States. PATIENTS: This study included 85,938 patients who underwent hip or knee arthroplasty or revision. INTERVENTION: Patients received enoxaparin, rivaroxaban, or aspirin as monotherapy for thromboprophylaxis. MEASUREMENTS: The primary outcome was all bleeding, classified as major or minor bleeding, occurring in the 40 days following surgery. The secondary outcome was venous thromboembolism. MAIN RESULTS: Among 85,938 patients, 10,465 received rivaroxaban, 14,047 received enoxaparin, and 61,426 received aspirin. Bleeding occurred in 126 (1.20%) patients with rivaroxaban, 253 (1.80%) with enoxaparin, and 611 (0.99%) with aspirin. There was a significant increase in odds of bleeding in the enoxaparin compared to aspirin group odds ratio (OR) 1.18, 95% confidence interval (CI) 1.01-1.38, p = 0.042), and a trend toward increased odds of bleeding in rivaroxaban compared to aspirin group (OR 1.21, 95% CI 0.99-1.47, p = 0.058) and rivaroxaban compared to enoxaparin (OR 1.03, 95% CI 0.82-1.28, p = 0.827). Odds of venous thromboembolism were not statistically significant between all three study medications. CONCLUSIONS: Among rivaroxaban, enoxaparin, and aspirin used for thromboprophylaxis in knee and hip arthroplasty or revision, aspirin had significantly decreased odds of bleeding complications compared to enoxaparin. Although not statistically significant, aspirin also had a trend toward decreased odds of bleeding complications compared to rivaroxaban. Our study results suggest that aspirin is a safer alternative for use in postoperative thromboprophylaxis following lower extremity joint arthroplasty or revision.

A Retrospective Analysis Comparing Post-Operative Bleeding with Various Doses of Aspirin after Lower Extremity Joint Arthroplasty or Revision.

STUDY OBJECTIVE: Previous studies have shown that aspirin is noninferior to other anticoagulation therapies in preventing postoperative venous thromboembolism following lower extremity arthroplasty or revision; however, its optimal dosing for this indication is less clear. This study aims to compare the odds of bleeding between different aspirin dosages following lower extremity joint arthroplasty or revision. DESIGN: This is a 3-year retrospective multi-center cohort study across the United States and its territories. SETTING: This study included patients admitted for total hip or knee arthroplasty or revision and were treated with prophylactic aspirin. PATIENTS, INTERVENTION, MEASUREMENTS: Patients were assigned to groups based on a total daily aspirin dose of 81, 162, 325, or 650 mg. Data were analyzed for postsurgical bleeding and thromboembolism events occurring during the initial admission and up to 40 days following surgery. Other exploratory variables included type of surgery, hip or knee arthroplasty, length of stay, and patient demographic data. MAIN RESULTS: Among 53,848 patients receiving aspirin, 3922 received a total daily dose of 81 mg, 19,341 received a total daily dose of 162 mg, 5256 received a total daily dose of 325 mg, and 25,329 received a total daily dose of 650 mg. Bleeding occurred in 466 (0.87%) patients and venous thromboembolism (VTE) in 209 patients (0.39%). The odds of bleeding were compared using logistic regression, with the 650-mg dose as the reference group. None were statistically significant for bleeding between all studied aspirin doses: 81 mg (OR 1.12, 95% CI 0.83-1.51, p = 0.451), 162 mg (OR 0.83, 95% CI 0.67-1.03, p = 0.097), and 325 mg (OR 0.83, 95% CI 0.59-1.13, p = 0.245). The odds of VTE were also not statistically significant: 81 mg (OR 0.71, 95% CI 0.40-1.17, p = 0.181), 162 mg (OR 0.75 95% CI 0.54-1.03, p = 0.072), and 325 mg (OR 1.00, 95% CI 0.64-1.53, p = 0.989). CONCLUSIONS: There were no significant differences in the odds of bleeding or venous thromboembolism among all studied aspirin dosages in patients receiving aspirin for thromboprophylaxis following lower extremity joint arthroplasty or revision.

Molecular Profiling Practices in Pancreatic Adenocarcinoma: Academic vs Community Physicians.

Background: Pancreatic adenocarcinoma (PDAC) is relatively rare but highly aggressive, with most patients diagnosed once they have metastatic or locally invasive disease. Molecular profiling is being explored as a tool for selecting patients for targeted therapy clinical trials and for assessing whether targeted therapies may be effective in PDAC. Whether molecular profiling is being performed at both academic and community oncology clinics has yet to be examined. Here, we characterized the molecular profiling practice patterns in patients with PDAC in academic versus community practices in Denver, Colorado. Methods: We retrospectively reviewed records of all patients with refractory, metastatic PDAC who were referred to a tertiary clinical trials drug development unit in Denver between 2014 and 2019. Results: Of 77 patients, 41 (55%) were men with a mean age of 65 years (SD, 9.3). Fifty-three patients (69%) were referred from the community and 20 (26%) from academic centers; 4 (5%) were self-referred. A total of 51% received profiling prior to referral; 29 of 50 (58%) were from the community and 10 of 21 (47%) from academic settings. Guardant was the most commonly ordered test (47 of 77; 61%); FoundationOne was the second most common (40 of 77; 52%). Twenty-three of 77 patients (30%) received both Guardant and FoundationOne testing, and 3 of 77 (4%) received Caris MI Profile. One patient received a Mocha assay and another received Ascend/Clarient fluorescence in situ hybridization (FISH). Four patients were self-referred, 2 of whom underwent both Guardant and FoundationOne, 1 who underwent Guardant testing only, and 1 who did not receive any molecular profiling testing. Conclusions: This study characterizes molecular profiling practice patterns in individuals with advanced PDAC who were referred to a tertiary clinical trials drug development unit. Both academic and community physicians were found to order profiling about 50% of the time. Further research is needed to determine impact on clinical trial enrollment and detection of PDAC.

Use of Statistical Power Analysis in Prospective and Retrospective Research.

JOGNN's Assistant Editor for Statistics reviews the use of power analysis for manuscripts submitted for publication consideration.

Surgeons' re-operative valve replacement practices in patients with endocarditis due to drug use.

BACKGROUND: This study discerns surgeons' attitudes and practices in the determination of heart valve replacement for patients with infectious endocarditis (IE) due to intravenous drug use (IVDU). We aimed to identify the factors contributing to surgeons' decision-making process for initial and recurrent surgical heart valves and the availability of institutional guidance. METHODS: An IRB-approved, anonymous mixed-methods, open survey instrument was designed and validated with 24 questions. A convenience sample of cardiothoracic surgeons in the United States and globally resulted in a total of 220 study participants with 176 completing every question on the survey. RESULTS: A cluster analysis revealed that although surgeons can be divided into subgroups based on their previous experience with valve replacements, these groups are not perfectly homogenous, and the number of identified clusters is dependent on technique used. Analysis of variance revealed the variables that most clearly divided the surgeons into subgroups were, in order of importance, years of practice, number of valve replacements, and geography. CONCLUSIONS: Our analysis showed heterogeneity among cardiothoracic surgeons regarding how they make clinical decisions regarding re-operative valve replacement related to IE-IVDU. Therefore, an opportunity exists for interprofessional teams to develop comprehensive guidelines to decrease variability in surgical decision-making regarding valve replacement associated with IE-IVDU.

Characterization of Blood-Based Molecular Profiling in Pancreatic Adenocarcinoma.

Background: Molecular profiling is being explored in pancreatic adenocarcinoma (PDAC) as a tool to assist with early detection, prognosis, and patient selection in targeted therapy clinical trials. Due to the challenges and risks of traditional tissue biopsies in pancreatic adenocarcinoma, the utility of blood-based molecular profiling is now being explored more broadly. However, given its novelty, what value blood-based molecular profiling may provide to oncologists caring for individuals with PDAC remains unknown. Herein, we characterize the mutational landscape of metastatic PDAC using blood-based circulating tumor DNA (ctDNA) collected in patients with refractory, metastatic PDAC who were referred to an oncology drug development unit in Denver, Colorado, between August 2014 and May 2019. Methods: We retrospectively analyzed results of blood-based molecular profiling that was performed on 77 consecutive patients with metastatic PDAC who underwent Guardant-360 testing for whom results were available. Results: In our data set, 55% of patients (41/77) were men, median (SD) age was 66 (9.3) years (range, 44-83). Of 77 patients, 34 (44%) had 1 or more somatic alterations. Variants reported as being of unknown significance were not included in the analyses. The total number of alterations were 119 (nonunique) and 96 (unique). The median number of alterations per patient was 3 and the median mutant allele frequency was 0.5%. TP53 was the most commonly altered gene (29 unique alterations), followed by KRAS (27 unique alterations). Of the patients with any alteration, 34% had 1 or more actionable alterations that could be potentially targeted in a clinical trial. Conclusions: Detection of genomic alterations in ctDNA from patients with metastatic PDAC is feasible and reveals a wide range of genomic alterations, the actionability of which is being explored in clinical trials. Further investigation is needed to determine the extent to which blood-based molecular profiling can provide clinical utility in helping to select patients into clinical trials and determine its impact on survival.

A Two-Year Longitudinal, Cross-Sectional Evaluation of Resident Physician Burnout: An Exploration of the Effects of Stress, Satisfaction, Exercise and EMR.

Background: There is a need for better understanding of trajectory of burnout in clinical training and what factors are associated with resident well-being and burnout overtime. This study examined medical resident burnout and physical activity throughout different times of the academic year, across several different medical specialties and postgraduate years (PGY), over two years. Methods: A resident wellness survey was administered throughout five different waves from summer 2018 to winter 2020. A total of 493 survey responses from seven subspecialties completed the survey. We used 474 responses for quantitative statistical analysis and 138 for qualitative thematic analysis. Results: The average response rate was 47%, and ranged between 40% (Wave 3) and 56% (Wave 1). Three analyses were conducted: the first demonstrated significantly higher Satisfaction in Wave 1 as opposed to Wave 2. The second analysis showed significant correlations between Overall, Satisfaction, and Stress scores and exercise-based questions for female, male, and primary care cohorts of residents. The third analysis showed that in 2018, interns and non-interns differed on Stress but did not differ on Satisfaction or Overall scores. Conclusions: Similar levels of satisfaction, stress, and overall well-being were reported at different times in the academic year and from year to year. Exercise was not consistently related to resident well-being outcomes. These findings suggest a need for targeted interventions based on post-graduate year, time in the academic year and well-being drivers.

Barriers to Clinical Trial Enrollment in Patients With Pancreatic Adenocarcinoma Eligible for Early-Phase Clinical Trials.

BACKGROUND: Early-phase clinical trials are critical to the advancement of cancer care, especially in patients with pancreatic ductal adenocarcinoma, given its aggressive nature and limited available therapeutic options. METHODS: A retrospective chart review of all patients with refractory or metastatic pancreatic ductal adenocarcinoma, referred to the Sarah Cannon Research Institute at HealthONE between 2014 and 2019, were reviewed. Patients who completed genomic profiling and qualified for a phase 1 trial (primarily 1a but some 1b) were identified to assess barriers to trial enrollment. RESULTS: Of 74 identified patients, 54 patients (73%) qualified for at least 1 clinical trial based on eligibility criteria and alterations detected via molecular profiling. Up to 40 industry-sponsored clinical trials were available during this time for consideration. Of the 54, 28 patients (52%) enrolled in a clinical trial, while 26 (48%) did not enroll. The most frequently cited barriers to enrollment were concerns regarding time commitment (12%), prolonged wait time for enrollment (12%), and fear of adverse events (8%). Seven of the 26 patients (27%) were lost to follow-up or had no stated reason for declining enrollment; others did not go on trial due to death/transition to hospice (n=5; 19%) or progression of disease/declining functional status (n=4; 15%). There were few statistically significant differences between patients who chose to go on trial and those who declined. CONCLUSIONS: An understanding of why eligible patients elect not to participate in early-phase clinical trials provides insight into the patient experience and can help identify misperceptions and areas for improvement in education and the clinical trial enrollment process.

Improving the Quality and Design of Retrospective Clinical Outcome Studies that Utilize Electronic Health Records.

Description Electronic health records (EHRs) are an excellent source for secondary data analysis. Studies based on EHR-derived data, if designed properly, can answer previously unanswerable clinical research questions. In this paper we will highlight the benefits of large retrospective studies from secondary sources such as EHRs, examine retrospective cohort and case-control study design challenges, as well as methodological and statistical adjustment that can be made to overcome some of the inherent design limitations, in order to increase the generalizability, validity and reliability of the results obtained from these studies.

Unscreened: Urgent and Emergent Surgical Outcomes in the Early COVID-19 Pandemic.

Background Creating useful recommendations for changes in surgical protocols during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been difficult due to a lack of studies based on representative samples. This study evaluates the clinical outcomes and characteristics of patients undergoing urgent or emergent surgeries. Methods This is a multi-center (eight-hospital), retrospective, observational study of urgent and emergent surgical patients from Colorado and Kansas, the United States, in the early stages of the SARS-CoV-2 pandemic. Patient groups were divided based on their coronavirus disease 2019 (COVID-19) status: positive, negative and untested. COVID-19 testing was performed after the surgery if patients were symptomatic. Results The analysis includes 5,547 patients who underwent surgery from March 1, 2020 to May 17, 2020. Seventy-four percent (4,096) were not tested for COVID-19 due to lack of symptoms. Out of the 1,451 tested patients, 1,412 tested negative, and 39 tested positive. Out of all the patients who tested positive, 69.23% were admitted to the intensive care unit (ICU), whereas 16.72% of untested and 21.25% of the negative patients. The invasive ventilation rate for the patients that tested positive was 46.15%, 4.22% for untested, and 8.85% for patients who tested negative. The mortality rate in the positive group was 7.69%, 1.10% in the untested group, and 1.56% in the positive group.    Conclusion Patients who tested positive for COVID-19 had worse clinical outcomes than patients who tested negative and untested. We recommend creating criteria for testing based on patient characteristics and surgical procedure rather than testing all patients awaiting surgery; this would allow us to conserve resources moving forward.

Summary of the First Annual Rocky Mountain Healthcare Symposium.

The Medical Center of Aurora, in Aurora, Colorado (USA), served as the host institution for the First Annual Rocky Mountain Healthcare Symposium. The objectives of the Symposium were to offer a series of lectures, provided by a group of internationally recognized leaders in clinical medical research on "How to conduct clinical medical research," and to allow medical residents from regional training programs to highlight their research. Twelve programs, from four US States, were represented. Oral presentations were given for selected abstracts with awards given for best posters and presentations. While the First Annual Symposium was generally viewed as successful based upon feedback metrics, survey results provided both subjective and quantitative foundation for improvements.

Correcting Hypokalemia in Hospitalized Patients Does Not Decrease Risk of Cardiac Arrhythmias.

BACKGROUND: It is currently standard practice to correct hypokalemia for the purpose of preventing cardiac arrhythmias in all hospitalized patients. However, the efficacy of this intervention has never been previously studied. OBJECTIVE: The objective of our study was to evaluate whether patients without acute coronary syndrome or history of arrhythmias were at increased risk of clinically significant cardiac arrhythmias if their potassium level was not corrected to ≥3.5 mEq/L. DESIGN: A retrospective case control study. SETTING: A community hospital. PARTICIPANTS: We enrolled selected patients who had episodes of hypokalemia during their hospital stay and were monitored on telemetry. Patients were split into groups based on success of replacing serum potassium to ≥3.5 mEq/L after 24 hours. MEASUREMENTS: The primary outcome was the development of an arrhythmia. Arrhythmias included supraventricular tachycardia, atrial fibrillation, atrial flutter, Mobitz type II second-degree or third-degree AV block, ventricular tachycardia, or ventricular fibrillation. A one-tailed Fisher's exact test and logistic regression were used for analysis. RESULTS: A total of 1338 hypokalemic patient days were recorded. Out of these days, 22 arrhythmia events (1.6% of patient days) were observed, 8 in the uncorrected group (1% patient days) and 14 in the corrected group (2.6% patient days). We found no statistically significant relationship between successfully correcting potassium to ≥3.5 mEq/L and number of arrhythmic events (p=0.037, OR = 2.38 (95% CI: 0.99, 6.03)). Logistic regression revealed that correction of potassium does not seem to be significantly related to arrhythmias (ß = 0.869, p=0.0517). CONCLUSIONS: In the acute care setting, we found that patients with hypokalemia whose potassium level did not correct to ≥3.5 mEq/L were not at increased odds of having an arrhythmia. This study suggests that the common practice of checking and replacing potassium is likely inconsequential.

Adherence to Universal Travel Screening in the Emergency Department During Epidemic Ebola Virus Disease.

BACKGROUND: During the 2014 West African Ebola Virus Disease (EVD) outbreak, the U.S. Centers for Disease Control and Prevention recommended that all emergency department (ED) patients undergo travel screening for risk factors of importing EVD. OBJECTIVES: We sought to determine the overall adherence rate to the recommended travel screening protocol and to identify factors associated with nonadherence to the protocol. METHODS: We conducted a multicenter, retrospective analysis of adherence to the travel screening program in an academic hospital and three affiliated community hospitals. A regression model identified patient and hospital factors associated with nonadherence. RESULTS: Of the 147,062 patients included for analysis, 93.7% (n = 137,834) had travel screenings completed. We identified several characteristics of patients that were most likely to be missed by the screening protocol-patients with low English proficiency, patients who arrive via ambulance or helicopter, and patients with more severe illness or injury based on initial triage acuity. CONCLUSIONS: These findings should be used to improve adherence to the travel screening protocol for future emerging infectious disease threats.