Implementing a Standardized Effect Size in the POLYSIBTEST Procedure.

A study was conducted to implement the use of a standardized effect size and corresponding classification guidelines for polytomous data with the POLYSIBTEST procedure and compare those guidelines with prior recommendations. Two simulation studies were included. The first identifies new unstandardized test heuristics for classifying moderate and large differential item functioning (DIF) for polytomous response data with three to seven response options. These are provided for researchers studying polytomous data using POLYSIBTEST software that has been published previously. The second simulation study provides one pair of standardized effect size heuristics that can be employed with items having any number of response options and compares true-positive and false-positive rates for the standardized effect size proposed by Weese with one proposed by Zwick et al. and two unstandardized classification procedures (Gierl; Golia). All four procedures retained false-positive rates generally below the level of significance at both moderate and large DIF levels. However, Weese's standardized effect size was not affected by sample size and provided slightly higher true-positive rates than the Zwick et al. and Golia's recommendations, while flagging substantially fewer items that might be characterized as having negligible DIF when compared with Gierl's suggested criterion. The proposed effect size allows for easier use and interpretation by practitioners as it can be applied to items with any number of response options and is interpreted as a difference in standard deviation units.

Characteristics of patients with hematologic malignancies without seroconversion post-COVID-19 third vaccine dosing.

Objectives: The objective of this study is to explore the characteristics of the subset of patients with hematologic malignancies (HMs) who had little to no change in SARS-CoV-2 spike antibody index value levels after a third mRNA vaccine dose (3V) and to compare the cohort of patients who did and did not seroconvert post-3V to get a better understanding of the demographics and potential drivers of serostatus. Study design: This retrospective cohort study analyzed SARS-CoV-2 spike IgG antibody index values pre and post the 3V data on 625 patients diagnosed with HM across a large Midwestern United States healthcare system between 31 October 2019 and 31 January 2022. Methods: To assess the association between individual characteristics and seroconversion status, patients were placed into two groups based on IgG antibody status pre and post the 3V dose, (-/+) and (-/-). Odds ratios were used as measures of association for all categorical variables. Logistic regressions were used to measure the association between HM condition and seroconversion. Results: HM diagnosis was significantly associated with seroconversion status (P = 0.0003) with patients non-Hodgkin lymphoma six times the odds of not seroconverting compared with multiple myeloma patients (P = 0.0010). Among the participants who were seronegative prior to 3V, 149 (55.6%) seroconverted after the 3V dose and 119 (44.4%) did not. Conclusion: This study focuses on an important subset of patients with HM who are not seroconverting after the COVID mRNA 3V. This gain in scientific knowledge is needed for clinicians to target and counsel these vulnerable patients.

Evaluating Pneumonitis Incidence in Patients with Non-small Cell Lung Cancer Treated with Immunotherapy and/or Chemotherapy Using Real-world and Clinical Trial Data.

Pneumonitis is a potentially life-threatening complication of anticancer therapy, and future treatment decisions may be informed by characterizing patients receiving therapies in the real-world setting. In this study, the incidence of treatment-associated pneumonitis (TAP) was compared among patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors (ICI) or chemotherapies in either of two settings: randomized clinical trials (RCT) or real world data (RWD)-based clinical practice. Pneumonitis cases were identified using International Classification of Diseases codes (for RWD), or the Medical Dictionary for Regulatory Activities preferred terms (for RCTs). TAP was defined as pneumonitis diagnosed during treatment or within 30 days of the last treatment administration. Overall TAP rates in the RWD cohort were lower [ICI: 1.9%; 95% confidence interval (CI), 1.2-3.2; chemotherapy: 0.8%; 95% CI, 0.4-1.6] than overall rates in the RCT cohort (ICI: 5.6%; 95% CI, 5.0-6.2; chemotherapy: 1.2%; 95% CI, 0.9-1.5). Overall RWD TAP rates were similar to grade 3+ RCT TAP rates (ICI: 2.0%; 95% CI, 1.6-2.3; chemotherapy: 0.6%; 95% CI, 0.4-0.9). In both cohorts, higher TAP incidence was observed among patients with a past medical history of pneumonitis than those without, regardless of treatment group. On the basis of this sizable study leveraging RWD, TAP incidence was low in the RWD cohort, likely in part due to methodology used for RWD focusing on clinically significant cases. Past medical history of pneumonitis was associated with TAP in both cohorts. Significance: Pneumonitis is a potentially life-threatening complication of anticancer treatment. As treatment options expand, management decisions become increasingly complex, and there is a greater need to understand the safety profiles of the treatment options in the real-world setting. Real-world data serve as an additional source of valuable information to complement clinical trial data and inform understanding of toxicity in patients with non-small cell lung cancer receiving ICIs or chemotherapies.

Quantifying the Value of the Molecular Tumor Board: Discordance Recommendation Rate and Drug Cost Avoidance.

PURPOSE: Molecular tumor boards (MTBs) provide interventions that assist the patient's primary oncologist's interpretation and application of precision oncology and avoid clinical and financial toxicities of prescribing inappropriate targeted therapy. In this article, we describe a novel method for illustrating MTBs value and recommendation discordance rate and report associated drug cost avoidance data. METHODS: From January 1, 2021, to December 31, 2021, patients assessed by our program's MTB were retrospectively evaluated. Recommendation discordance was defined as any disagreement between MTB therapeutic recommendations and those provided in the next-generation sequencing vendor's report. RESULTS: In 2021, our program processed 1,119 next-generation sequencing orders via external vendors for 1,029 unique patients with a variety of solid tumor and hematologic malignancies. During this period, 962 patients were reviewed through our MTB process. MTB recommendation discordance rate was high (229 of 502; 45.6%) and varied across test vendors. Rationales for discordance included the following: low level of evidence (88% of patients), alternative standard of care available (60%), and tolerability concerns (42%), among others. Discordance was highest for Vendor C (30%), followed by Vendor A (24%) and Vendor B (8%). The most common drug classes not supported were mTOR, PARP, MEK, and PIK3CA inhibitors when recommended by vendors in off-label settings. MTB interventions accounted for $3,209,070 in US dollars in potential drug cost avoidance. CONCLUSION: Therapeutic recommendation discordance rates can provide quantitative insight into the benefit of MTB. Discordance-associated drug cost avoidance further demonstrates MTB's financial value. These measures may be used as part of the justification for this service line within a cancer care program.

Real-World Third COVID-19 Vaccine Dosing and Antibody Response in Patients With Hematologic Malignancies.

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer's or Moderna's COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics. Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus. Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive from prior negative following the third dose (-/+). The remaining 104 (21.1%) were seronegative both before and after 3V (-/-). No participant was seropositive pre-3V and seronegative post-3V (+/-). Results showed a statistically significant increase in the proportion of seropositivity after receiving a third COVID-19 vaccine (P<0.00001). Response to 3V was significantly associated with the 3V vaccine type (P=0.0006), previous COVID-19 infection (P=0.0453), and malignancy diagnosis (P<0.0001). Likelihood of seroconversion (-/+) after 3V was higher in the group of patients with multiple myeloma or related disorders compared to patients with lymphoid leukemias (odds ratio: 8.22, 95% CI: 2.12-31.79; P=0.0008). Conclusions: A third COVID-19 vaccination is effective in producing measurable seroconversion in many patients with hematologic malignancies. Oncologists should actively encourage all their patients, especially those with multiple myeloma, to receive a 3V, given the high likelihood of seroconversion.

Reevaluating the SIBTEST Classification Heuristics for Dichotomous Differential Item Functioning.

A simulation study was conducted to investigate the heuristics of the SIBTEST procedure and how it compares with ETS classification guidelines used with the Mantel-Haenszel procedure. Prior heuristics have been used for nearly 25 years, but they are based on a simulation study that was restricted due to computer limitations and that modeled item parameters from estimates of ACT and ASVAB tests from 1987 and 1984, respectively. Further, suggested heuristics for data fitting a two-parameter logistic model (2PL) have essentially went unused since their original presentation. This simulation study incorporates a wide range of data conditions to recommend heuristics for both 2PL and three-parameter logistic (3PL) data that correspond with ETS's Mantel-Haenszel heuristics. Levels of agreement between the new SIBTEST heuristics and Mantel-Haenszel heuristics were similar for 2PL data and higher than prior SIBTEST heuristics for 3PL data. The new recommendations provide higher true-positive rates for 2PL data. Conversely, they displayed decreased true-positive rates for 3PL data. False-positive rates, overall, remained below the level of significance for the new heuristics. Unequal group sizes resulted in slightly larger false-positive rates than balanced designs for both prior and new SIBTEST heuristics, with rates less than alpha levels for equal ability distributions and unbalanced designs versus false-positive rates slightly higher than alpha with unequal ability distributions and unbalanced designs.

Rates of Forced Sexual Experiences Among High School Students From 2001 to 2019.

Public awareness of sexual assault and initiatives aimed at preventing sexual assault continue to increase over the years. However, whether rates of sexual assault have diminished because of such cultural shifts remains unclear. The purpose of this study was to assess if rates of sexual assault (i.e., forced sex) have changed over the past 18 years for adolescent girls and boys as well as potential differences across racial/ethnic identities. Using nationally representative data from the Youth Risk Behavioral Surveillance Survey from 2001 to 2019, we conducted logistic regressions to assess rates of experiences of forced sex by sex and by sex and racial/ethnic identity, while accounting for grade level. Participants included 135,837 high school students. From 2001 to 2019, rates of forced sex maintained for girls; however, there was a decrease over time for boys. For girls, there were inconsistent differences in rates of forced sex by racial/ethnic identities. However, boys who identified as Black, Hispanic, Multi-Racial, and Other Race/Ethnicity were at higher risk to report forced sex than their White peers, until 2015; only Other Race/Ethnicity was at higher risk in 2019. As girls and boys aged, the risk of forced sex increased. Despite prevention efforts, rates of forced sex did not decrease from 2001 to 2019 for adolescent girls disregarding race/ethnicity, and for racial/ethnic minority boys. That rates of forced sex continue to be high is problematic as experiencing sexual assault at an earlier age is associated with myriad consequences. Further, results suggest current prevention initiatives may be inadequate at addressing risk factors for forced sex, and more broadly, sexual assault. Moving forward, researchers and educators may want to re-evaluate the strategies used to address and measure sexual assault experiences.

DIFSIB: A SIBTEST Package.

The R package DIFSIB provides a direct translated version of the SIBTEST, Crossing- SIBTEST, and POLYSIBTEST procedures that were last updated and released in 2005. Having these functions directly written from Fortran into R code will allow researchers and practitioners to easily access the most recent versions of these procedures when they are conducting differential item functioning analysis and continue to improve the software more easily.

Abortion vs. Sexual Assault: People's Perceptions of Kavanaugh's Nomination to the Supreme Court of the United States.

Public reaction to Brett Kavanaugh's nomination to the Supreme Court of the United States initially centered around abortion. However, approximately two months after the nomination, sexual assault accusations against Kavanaugh were made public. We examined the extent that people's perceptions of Kavanaugh's stance on abortion and people's attitudes toward whether Kavanaugh committed sexual assault were associated with perceptions of Kavanaugh as a good Supreme Court justice. Data were collected from English- and Spanish-speaking participants (N = 2,883) in the United States via Qualtrics' panel. Using an exploratory hierarchical regression approach, we found that people's perceptions of whether Kavanaugh committed sexual assault was a stronger predictor of their attitudes toward Kavanaugh's quality as a Supreme Court justice [F(1,2855) = 1736.54, p < .001] than people's perceptions of him regarding abortion, after controlling for demographic characteristics and participants' abortion identity (e.g., identifying as pro-life, pro-choice). That sexual assault was a stronger predictor could suggest the importance of sexual assault regarding opinions of Supreme Court justices or potential over inflation of abortion as a salient issue. Researchers should investigate the saliency of sexual and reproductive health issues in relation to Supreme Court nominees.

Rapid real-world data analysis of patients with cancer, with and without COVID-19, across distinct health systems.

BACKGROUND: The understanding of the impact of COVID-19 in patients with cancer is evolving, with need for rapid analysis. AIMS: This study aims to compare the clinical and demographic characteristics of patients with cancer (with and without COVID-19) and characterize the clinical outcomes of patients with COVID-19 and cancer. METHODS AND RESULTS: Real-world data (RWD) from two health systems were used to identify 146 702 adults diagnosed with cancer between 2015 and 2020; 1267 COVID-19 cases were identified between February 1 and July 30, 2020. Demographic, clinical, and socioeconomic characteristics were extracted. Incidence of all-cause mortality, hospitalizations, and invasive respiratory support was assessed between February 1 and August 14, 2020. Among patients with cancer, patients with COVID-19 were more likely to be Non-Hispanic black (NHB), have active cancer, have comorbidities, and/or live in zip codes with median household income <$30 000. Patients with COVID-19 living in lower-income areas and NHB patients were at greatest risk for hospitalization from pneumonia, fluid and electrolyte disorders, cough, respiratory failure, and acute renal failure and were more likely to receive hydroxychloroquine. All-cause mortality, hospital admission, and invasive respiratory support were more frequent among patients with cancer and COVID-19. Male sex, increasing age, living in zip codes with median household income <$30 000, history of pulmonary circulation disorders, and recent treatment with immune checkpoint inhibitors or chemotherapy were associated with greater odds of all-cause mortality in multivariable logistic regression models. CONCLUSION: RWD can be rapidly leveraged to understand urgent healthcare challenges. Patients with cancer are more vulnerable to COVID-19 effects, especially in the setting of active cancer and comorbidities, with additional risk observed in NHB patients and those living in zip codes with median household income <$30 000.

Coordinating an Oncology Precision Medicine Clinic Within an Integrated Health System: Lessons Learned in Year One.

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual's genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM's potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health care system (Aurora Health Care, Milwaukee, WI) comprised of multiple hospitals and clinics. We also report our experience implementing a specific OPM software platform used to embed molecular panel data into patients' electronic medical records.

Improving Quality Metric Adherence to Minimally Invasive Breast Biopsy among Surgeons Within a Multihospital Health Care System.

BACKGROUND: Minimally invasive breast biopsy (MIBB) is the procedure of choice for diagnosing breast lesions indeterminate for malignancy. Multihospital health care systems face challenges achieving systemwide adherence to standardized guidelines among surgeons with varying practice patterns. This study tested whether providing individual feedback about surgeons' use of MIBB to diagnose breast malignancies improved quality metric adherence across a large health care organization. STUDY DESIGN: We conducted a prospective matched-pairs study to test differences (or lack of agreement) between periods before and after intervention. All analytical cases of primary breast cancer diagnosed during 2011 (period 1) and from July 2012 to June 2013 (period 2) across a multihospital health care system were reviewed for initial diagnosis by MIBB or open surgical biopsy. Open surgical biopsy was considered appropriate care only if MIBB could not be performed for reasons listed in the American Society of Breast Surgeons' quality measure for preoperative diagnosis of breast cancer. Individual and systemwide results of adherence to the MIBB metric during period 1 were sent to each surgeon in June 2012 and were later compared with period 2 results using McNemar's test of marginal homogeneity for matched binary responses. RESULTS: Forty-six surgeons were evaluated on use of MIBB to diagnose breast cancer. In period 1, metric adherence for 100% of cases was achieved by 37 surgeons, for a systemwide 100% compliance rate of 80.4%. After notification of individual performance, 44 of 46 surgeons used MIBB solely or otherwise appropriate care to diagnose breast cancer, which improved systemwide compliance to 95.7%. CONCLUSIONS: Providing individual and systemwide performance results to surgeons can increase self-awareness of practice patterns when diagnosing breast cancer, leading to standardized best-practice care across a large health care organization.

MGMT inhibition suppresses survivin expression in pancreatic cancer.

OBJECTIVES: Survivin, an antiapoptotic gene inhibited by p53, is overexpressed in human cancers and correlates with chemotherapy resistance. Here, we investigated the mutual regulatory mechanism between MGMT (O-methylguanine DNA methyltransferase) and survivin. METHODS: This study used standard techniques for protein and messenger RNA levels, promoter activity, protein-DNA interaction, cell viability, and correlative animal model. RESULTS: O-benzylguanine (BG), a potent inhibitor of MGMT (a DNA repair protein), curtails the expression of survivin in pancreatic cancer. Silencing MGMT by small interfering RNA down-regulates survivin transcription. p53 inhibition enhances MGMT and survivin expressions. When p53 was silenced, BG-induced MGMT inhibition was not associated with the down-regulation of survivin, underscoring the regulatory role of p53 in the MGMT-survivin axis. O-benzylguanine inhibits survivin and PCNA (proliferating cell nuclear antigen) at messenger RNA and protein levels in PANC-1 and L3.6pl cells and decreases survivin promoter activity via increased p53 recruitment to the survivin promoter. In orthotopic pancreatic xenografts established in nude mice, BG ± gemcitabine (GEM) decrease survivin expression in tumor tissue; protein levels and immunohistochemistry show significant decrease in survivin and PCNA levels, which correlate with increased sensitivity to GEM. CONCLUSIONS: MGMT inhibition is associated with decrease in survivin expression and increase in sensitivity to GEM in pancreatic cancer.

Postoperative ileus-related morbidity profile in patients treated with alvimopan after bowel resection.

BACKGROUND: Postoperative ileus (POI), an interruption of coordinated bowel motility after operation, is exacerbated by opioids used to manage pain. Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerated gastrointestinal (GI) recovery after bowel resection in randomized, double-blind, placebo-controlled, multicenter phase III POI trials. The effect of alvimopan on POI-related morbidity for patients who underwent bowel resection was evaluated in a post-hoc analysis. STUDY DESIGN: Incidence of POI-related postoperative morbidity (postoperative nasogastric tube insertion or POI-related prolonged hospital stay or readmission) was analyzed in four North American trials for placebo or alvimopan 12 mg administered 30 minutes or more preoperatively and twice daily postoperatively until hospital discharge (7 or fewer postoperative days). GI-related adverse events and opioid consumption were summarized for each treatment. Estimations of odds ratios of alvimopan to placebo and number needed to treat (NNT) to prevent one patient from experiencing an event of POI-related morbidity were derived from the analysis. RESULTS: Patients receiving alvimopan 12 mg were less likely to experience POI-related morbidity than patients receiving placebo (odds ratio = 0.44, p < 0.001). Fewer patients receiving alvimopan (alvimopan, 7.6%; placebo, 15.8%; NNT = 12) experienced POI-related morbidity. There was a lower incidence of postoperative nasogastric tube insertion, and other GI-related adverse events on postoperative days 3 to 6 in the alvimopan group than the placebo group. Opioid consumption was comparable between groups. CONCLUSIONS: Alvimopan 12 mg was associated with reduced POI-related morbidity compared with placebo, without compromising opioid-based analgesia in patients undergoing bowel resection. Relatively low NNTs are clinically meaningful and reinforce the potential benefits of alvimopan for the patient and health care system.

Histochemical alterations in one lung ventilation.

BACKGROUND: One lung ventilation is a commonly performed surgical procedure. Although there have been several reports showing that one-lung ventilation can cause pathophysiological alterations such as pulmonary hypoxic vasoconstriction and intrapulmonary shunting, there have been virtually no reports on the effects of one-lung ventilation on lung histology. MATERIALS AND METHODS: Yorkshire pigs (11-17 kg) were anesthetized, a tracheotomy performed and a tracheal tube inserted. The chest was opened and one lung ventilation (OLV), was induced by clamping of the right main bronchus. OLV was continued for 60 min before the clamp was removed and two lung ventilation (TLV) started. TLV was continued for 30 to 60 min. Blood and lung biopsies were taken immediately before OLV, 30 min and 60 min of OLV and after restoration of TLV. RESULTS: Histological analyses revealed that the non-ventilated lung was totally collapsed during OLV. On reventilation, there was clear evidence of vascular congestion and alveolar wall thickening at 30 min after TLV. At 60 min of TLV, there was still vascular congestion. Serum nitrite levels (as an index of nitric oxide production) showed steady decline over the course of the experimental period, reaching a significantly low level on reventilation (compared with baseline levels before OLV). Lung MPO activity (marker of neutrophil sequestration) and serum TNFalpha levels were not raised during the entire experimental period. CONCLUSIONS: These results suggest that there was lung vascular injury after OLV, which was associated with reduced levels of nitric oxide production and not associated with an inflammatory response.

Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery.

PURPOSE: Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus. METHODS: Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study. RESULTS: Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group. CONCLUSIONS: In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.