Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. RESULTS: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). CONCLUSION: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).

Time to Move Beyond a Binary Criterion for Gestational Diabetes?

Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM.

Cholecystectomy clip-induced biliary stone: Case report and literature review.

ABSTRACT: Migration of cholecystectomy surgical clip into the common bile duct with subsequent stone formation is a rare phenomenon, one which may lead to complications including obstruction, pain, nausea, vomiting and fever. The mechanism of migration is largely unknown but may result from a combination of factors including necrosis, intra-abdominal pressure or poor surgical technique with migrated clip serving as a nidus for stone formation. We present a 55-year-old woman with clip-induced stone impacted at the distal common bile duct 12 years post-cholecystectomy and a review of the literature related to cholecystectomy clip stone formation. In addition, we reviewed relevant English language case reports and literature reviews by searching PubMed using search terms 'stone', 'clip', 'cholecystectomy' and 'biliary'. There was no limit to the date of publication. Our study found 68 unduplicated cases of clip-induced stones which had a wide range of onset and presenting systems. Further research is needed to identify risk factors, methods of prevention and benefits of early detection screening.

The Landscape of Pediatric Radiation Oncology in Nigeria.

Radiation therapy (RT) is an essential part of the multidisciplinary treatment of pediatric cancer. Over the past five decades, significant advances have been made in the delivery of RT, with better dose delivery to disease targets while minimizing exposure to nearby organs at risk. These advances have led to improved treatment outcomes, increased survival, and reduced treatment-related toxicities. Advanced treatment techniques, however, require significant investment in infrastructural and personnel resources. This review documents what is currently available regarding expertise and infrastructure for pediatric radiation oncology practice in Nigeria. It was performed to serve as a foundation for the creation and design of tailored solutions (initiatives and policies) to increase pediatric radiation availability, accessibility, and equity in Nigeria and ultimately improve pediatric cancer treatment outcomes in the region.

Use of conditional estimates of effect in cancer epidemiology: An application to lung cancer treatment.

BACKGROUND: In oncology clinical trials, there is the assumption that randomization sufficiently balances confounding covariates and therefore average treatment effects are usually reported. This paper explores the wider benefits provided by conditioning on covariates for reasons other than mitigation of confounding. METHODS: We reanalyzed the data from primary randomized controlled trials listed in two meta-analyses to explore the significance of conditioning on smoking status in terms of the effect magnitude of treatment on progression free survival in non-small cell lung cancer. RESULTS: The reanalysis revealed that conditioning on smoking status using sub-group analyses provided the closest empiric estimate of individual treatment effect based on smoking status and significantly reduced the heterogeneity of treatment effect observed across studies. In addition, smoking status was determined to be a modifier of the effect of treatment. CONCLUSION: Conditioning on prognostic covariates in randomized trials in oncology helps generate the closest empiric estimates of individual treatment benefit, addresses heterogeneity due to varying covariate distributions across trials and facilitates future decision making as well as evidence synthesis. Conditioning using sub-group analyses also allows examination for effect modification in meta-analysis.

Development of an evidence-based model for predicting patient, provider, and appointment factors that influence no-shows in a rural healthcare system.

BACKGROUND: No-show appointments pose a significant challenge for healthcare providers, particularly in rural areas. In this study, we developed an evidence-based predictive model for patient no-shows at the Marshfield Clinic Health System (MCHS) rural provider network in Wisconsin, with the aim of improving overbooking approaches in outpatient settings and reducing the negative impact of no-shows in our underserved rural patient populations. METHODS: Retrospective data (2021) were obtained from the MCHS scheduling system, which included 1,260,083 total appointments from 263,464 patients, as well as their demographic, appointment, and insurance information. We used descriptive statistics to associate variables with show or no-show status, logistic regression, and random forests utilized, and eXtreme Gradient Boosting (XGBoost) was chosen to develop the final model, determine cut-offs, and evaluate performance. We also used the model to predict future no-shows for appointments from 2022 and onwards. RESULTS: The no-show rate was 6.0% in both the train and test datasets. The train and test datasets both yielded 5.98. Appointments scheduled further in advance (> 60 days of lead time) had a higher (7.7%) no-show rate. Appointments for patients aged 21-30 had the highest no-show rate (11.8%), and those for patients over 60 years of age had the lowest (2.9%). The model predictions yielded an Area Under Curve (AUC) of 0.84 for the train set and 0.83 for the test set. With the cut-off set to 0.4, the sensitivity was 0.71 and the positive predictive value was 0.18. Model results were used to recommend 1 overbook for every 6 at-risk appointments per provider per day. CONCLUSIONS: Our findings demonstrate the feasibility of developing a predictive model based on administrative data from a predominantly rural healthcare system. Our new model distinguished between show and no-show appointments with high performance, and 1 overbook was advised for every 6 at-risk appointments. This data-driven approach to mitigating the impact of no-shows increases treatment availability in rural areas by overbooking appointment slots on days with an elevated risk of no-shows.

Sponsor Perspectives on the Impact of the COVID-19 Pandemic on Interventional Cancer Clinical Trial Protocols and Data Quality.

PURPOSE: The onset of the COVID-19 pandemic created major disruptions in the conduct of cancer clinical trials. In response, regulators and sponsors allowed modifications to traditional trial processes to enable clinical research and care to continue. We systematically evaluated how these mitigation strategies affected data quality and overall trial conduct. METHODS: This study used surveys and live interviews. Forty-one major industry and National Cancer Institute Network groups (sponsors) overseeing anticancer treatment trials open in the United States from January 2015 to May 2022 were invited to participate. Descriptive statistics were used for survey data summaries. Key themes from interviews were identified. RESULTS: Twenty sponsors (48.8%; 15 industry and five Network groups) completed the survey; 11/20 (55.0%) participated in interviews. Sponsors predominantly (n = 12; 60.0%) reported large (≥11 trials) portfolios of phase II and/or phase III trials. The proportion of sponsors reporting a moderate (9) or substantial (8) increase in protocol deviations in the initial pandemic wave versus the pre-pandemic period was 89.5% (17/19); the proportion reporting a substantial increased dropped from 42.1% (n = 8/19) in the initial wave to 15.8% (n = 3/19) thereafter. The most commonly adopted mitigation strategies were remote distribution of oral anticancer therapies (70.0%), remote adverse event monitoring (65.0%), and remote consenting (65.0%). Most respondents (15/18; 83.3%) reported that the pandemic had minimal (n = 14) or no impact (n = 1) on overall data integrity. CONCLUSION: Despite nearly all sponsors observing a temporary increase in protocol deviations, most reported the pandemic had minimal/no impact on overall data integrity. The COVID-19 pandemic accelerated an emerging trend toward greater flexibility in trial conduct, with potential benefits of reduced burden on trial participants and sites and improved patient access to research.

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment. Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602).

PURPOSE: A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used. MATERIALS AND METHODS: A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%. RESULTS: A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist. CONCLUSION: This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Examining Cancer Patients' Perceptions of the Impact of COVID-19 on Teleoncology: Findings From 15 Nigerian Outpatient Cancer Clinics.

PURPOSE: To examine cancer patients' perspectives on the impact of COVID-19 on teleoncology in Nigeria. METHODS: Data from a multicenter survey conducted at 15 outpatient clinics to 1,097 patients with cancer from April and July 2020 were analyzed. The study outcome was telemedicine, defined as patients who reported their routine follow-up visits were converted to virtual visits because of COVID-19 (coded yes/no). Covariates included patient age, ethnicity, marital status, income, cancer treatment, service disruption, and cancer diagnosis/type. Stata/SE.v.17 (StataCorp, College Station, TX) was used to perform chi-square and logistic regression analyses. P values ≤ .05 were considered statistically significant. RESULTS: The majority of the 1,097 patients with cancer were female (65.7%) and age 55 years and older (35.0%). Because of COVID-19, 12.6% of patients' routine follow-ups were converted to virtual visits. More patients who canceled/postponed surgery (17.7% v 7.5%; P ≤ .001), radiotherapy (16.9% v 5.3%; P ≤ .001), and chemotherapy (22.8% v 8.5%; P ≤ .001), injection chemotherapy (20.6% v 8.7%; P ≤ .001) and those who reported being seen less by their doctor/nurse (60.3% v 11.4%; P ≤ .001) reported more follow-up conversions to virtual visits. In multivariate analyses, patients seen less by their doctors/nurses were 14.3 times more likely to have their routine follow-ups converted to virtual visits than those who did not (odds ratio, 14.33; 95% CI, 8.36 to 24.58). CONCLUSION: COVID-19 caused many patients with cancer in Nigeria to convert visits to a virtual format. These conversions were more common in patients whose surgery, radiotherapy, chemotherapy, and injection chemotherapy treatments were canceled or postponed. Our findings suggest how COVID-19 affects cancer treatment services and the importance of collecting teleoncological care data in Nigeria.

Your neighborhood matters: an ecological social determinant study of the relationship between residential racial segregation and the risk of firearm fatalities.

BACKGROUND: Firearm fatalities are a major public health concern, claiming the lives of 40,000 Americans each year. While firearm fatalities have pervasive effects, it is unclear how social determinants of health (SDOH) such as residential racial segregation, income inequality, and community resilience impact firearm fatalities. This study investigates the relationships between these SDOH and the likelihood of firearm fatalities. METHODS: County-level SDOH data from the Agency for Health Care Research and Quality for 2019 were analyzed, covering 72 Wisconsin counties. The dependent variable was the number of firearm fatalities in each county, used as a continuous variable. The independent variable was residential racial segregation (Dissimilarity Index), defined as the degree to which non-White and White residents were distributed across counties, ranging from 0 (complete integration) to 100 (complete segregation), and higher values indicate greater residential segregation (categorized as low, moderate, and high). Covariates were income inequality ranging from zero (perfect equality) to one (perfect inequality) categorized as low, moderate, and high, community resilience risk factors (low, moderate, and high risks), and rural-urban classifications. Descriptive/summary statistics, unadjusted and adjusted negative binomial regression adjusting for population weight, were performed using STATA/MPv.17.0; P-values ≤ 0.05 were considered statistically significant. ArcMap was used for Geographic Information System analysis. RESULTS: In 2019, there were 802 firearm fatalities. The adjusted model demonstrates that the risk of firearm fatalities was higher in areas with high residential racial segregation compared to low-segregated areas (IRR.:1.26, 95% CI:1.04-1.52) and higher in areas with high-income inequality compared to areas with low-income inequality (IRR.:1.18, 95% CI:1.00-1.40). Compared to areas with low-risk community resilience, the risk of firearm fatalities was higher in areas with moderate (IRR.:0.61, 95% CI:0.48-0.78), and in areas with high risk (IRR.:0.53, 95% CI:0.41-0.68). GIS analysis demonstrated that areas with high racial segregation also have high rates of firearm fatalities. CONCLUSION: Areas with high residential racial segregation have a high rate of firearm fatalities. With high income inequality and low community resilience, the likelihood of firearm fatalities increases.

Evaluating the adoption of voice recognition technology for real-time dictation in a rural healthcare system: A retrospective analysis of dragon medical one.

BACKGROUND: In 2013, Marshfield Clinic Health System (MCHS) implemented the Dragon Medical One (DMO) system provided by Nuance Management Center (NMC) for Real-Time Dictation (RTD), embracing the idea of streamlined clinic workflow, reduced dictation hours, and improved documentation legibility. Since then, MCHS has observed a trend of reduced time in documentation, however, the target goal of 100% adoption of voice recognition (VR)-based RTD has not been met. OBJECTIVE: To evaluate the uptake/adoption of VR technology for RTD in MCHS, between 2018-2020. METHODS: DMO data for 1,373 MCHS providers from 2018-2020 were analyzed. The study outcome was VR uptake, defined as the median number of hours each provider used VR technology to dictate patient information, and classified as no/yes. Covariates included sex, age, US-trained/international medical graduates, trend, specialty, and facility. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed. Stata/SE.version.17 was used for analyses. P-values less than/equal to 0.05 were considered statistically significant. RESULTS: Of the 1,373 MCHS providers, the mean (SD) age was 48.3 (12.4) years. VR uptake was higher than no uptake (72.0% vs. 28.0%). In both unadjusted and adjusted analyses, VR uptake was 4.3 times and 7.7 times higher in 2019-2020 compared to 2018, respectively (OR:4.30,95%CI:2.44-7.46 and AOR:7.74,95%CI:2.51-23.86). VR uptake was 0.5 and 0.6 times lower among US-trained physicians compared to internationally-trained physicians (OR:0.53,95%CI:0.37-0.76 and AOR:0.58,95%CI:0.35-0.97). Uptake was 0.2 times lower among physicians aged 60/above than physicians aged 29/less (OR:0.20,95%CI:0.10-0.59, and AOR:0.17,95%CI:0.27-1.06). CONCLUSION: Since 2018, VR adoption has increased significantly across MCHS. However, it was lower among US-trained physicians than among internationally-trained physicians (although internationally physicians were in minority) and lower among more senior physicians than among younger physicians. These findings provide critical information about VR trends, physician factors, and which providers could benefit from additional training to increase VR adoption in healthcare systems.

Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.

BACKGROUND: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction. METHODS: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients. RESULTS: Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low. CONCLUSIONS: The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.

Therapies activating the immune system (checkpoint inhibitors) have revolutionized the treatment of patients with advanced cancer, however new molecular tests may better identify patients who could benefit. Using treatment data and clinical molecular test results, we report the development and validation of Immunotherapy Response Score (IRS) to predict checkpoint inhibitor benefit. Across patients with more than 20 advanced cancer types, IRS better predicted checkpoint inhibitor benefit than currently available tests. Data from >20,000 patients showed that IRS identifies ~8% of patients with advanced cancer who may dramatically benefit from checkpoint inhibitors but would not receive them today based on currently available tests. Our approach may help clinicians to decide which patients should receive checkpoint inhibitors to treat their disease.

Distance Matters: Investigating No-Shows in a Large Rural Provider Network.

Background/Objective: No-shows have a negative effect on healthcare outcomes. It is unclear, however, whether patients' distance from the clinic is associated with higher no-show rates. To fill this knowledge gap, we examined the relationship between patients' distance from the clinic and no-shows in a rural provider network.Methods: Data from Marshfield Clinic Health System's scheduling system, including 263,464 recent patient appointments in 2021 were analyzed. The outcome was no-shows, defined as when patients missed an appointment (categorized as yes/no). The exposure was the distance to the clinic, measured in miles as a straight-line distance from the clinic in the patient's zip code to the facility where the appointment was held (classified as <5 miles, 5-10, 10-20; >20, and used as continuous). Covariates were patient demographics, appointments, providers, and insurance status. Chi-square and logistic regression were used with p-values ≤.05 considered statistically significant.Results: The no-show rate was 8.0%. Patients who lived <5 miles (8.3%) and >20 miles (8.2%) from the clinic had higher no-show rates than those who lived between 10-20 miles (8.0%) and 5-10 miles (7.6%), at P=0.001. In the adjusted model, the odds of no-show were similar between patients who did not show and those who did (OR:1.00,95%CI:1.00-1.00). No-shows were more likely among male patients compared to females (OR:1.14,95%CI:1.11-1.18), Spanish compared to English speakers (OR:1.34,95%CI:1.20-1.50), prior no-show compared to no prior no-show (OR:4.42,95%CI:4.27-4.48), >4 weeks lead time compared to <1 day (OR:5.45,95%CI:4.98-5.97), and Medicaid compared to non-Medicaid patients (OR:1.56,95%CI:1.49-1.63).Conclusion: Our analysis showed patients who lived <5 miles and >20 miles from the clinic had higher no-show rates. The odds of a no-show were comparable between patients who showed up and those who did not. Male patients, Spanish-speaking patients, patients with a history of no-shows, and Medicaid beneficiaries were more likely to miss their appointments. Understanding the impact of these variables on no-show rates can assist healthcare providers in developing strategies to improve patient access and reduce no-show rates. These findings imply that rural patients may face a variety of barriers when seeking healthcare, necessitating a comprehensive approach to addressing this issue.

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.

PURPOSE: To quantify the relationship between diabetes and fatigue from pre-chemotherapy to 6 months post-chemotherapy for women with breast cancer compared to women without a history of cancer (controls). METHODS: This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and controls. Diabetes diagnosis (yes/no) was obtained at baseline, and cancer-related fatigue was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6 months post-chemotherapy in patients; controls were assessed at equivalent time points. Repeated measures mixed effects models estimated the association between fatigue and diabetes controlling for cancer (yes/no), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education. RESULTS: Among 439 patients and 235 controls (52.8 ± 10.5 years old), diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). At baseline, diabetes was associated with worse fatigue (4.1 ± 1.7 points, p = 0.017). Also, diabetes was associated with clinically meaningful worse fatigue throughout the study period among all participants (5.2 ± 1.9 points, p = 0.008) and patients alone (4.5 ± 2.0, p = 0.023). For the MFSI subdomains among patients, diabetes was associated with worse general (p = 0.005) and mental fatigue (p = 0.026). CONCLUSIONS: Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe cancer-related fatigue in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address cancer-related fatigue during chemotherapy treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01382082, first posted June 27, 2011.

Patient's Perspective on the Impact of COVID-19 on Cancer Treatment in Nigeria.

PURPOSE: Because of the global COVID-19 pandemic, health care organizations introduced guidelines for modifications to health and cancer medical care delivery to mitigate transmission and ensure quality health outcomes. To examine the extent and impact of these modifications on oncology service disruptions in Nigeria, we surveyed oncology patients across selected public and private cancer treatment centers. MATERIALS AND METHODS: Participating in the study were 15 tertiary cancer treatment centers across 12 Nigerian states. We recruited adult patients with cancer (18+ years) on active treatment to complete a self-administered survey on cancer care during COVID-19. We conducted descriptive and multivariate data analysis using Stata 16.1. RESULTS: Respondents were (n = 1,072), female (65.7%), ages 18-49 years (50.3%), and married (80.7%). The top two cancers were breast and prostate. Overall, 17.3% of respondents reported disruptions to cancer care, and more than half (51.0%) reported difficulties accessing care. Changes in chemotherapy regimens or route of administration were reported in 8.4% of respondents. Odds for any disruption were highest for older patients, western states, patients with prostate cancer, and patients with two or more flu symptoms. Odds for radiotherapy cancellation were highest for older patients, those with prostate cancer, and those with medium service perception. CONCLUSION: This study investigated COVID-19-influenced cancer treatment disruptions in Nigeria. Patients with cancer experienced significant disruptions to cancer care. Vulnerable patients are most likely to be negatively affected. Policies and strategies aimed at minimizing service disruptions while maintaining cancer patients' safety should be a priority for all health care institutions in the COVID-19 era.

Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy.

Objective: Within the last decade, the use of ibrutinib, a first-generation, non-selective, irreversible Burton's tyrosine kinase inhibitor for the treatment of hematological malignancies has proven highly effective in improving patient outcomes.Background: Ibrutinib has been associated with an increase in atrial fibrillation (AF). The predisposing factors are thought to be pre-existing cardiovascular risk factors, but these have not been directly evaluated.Methods: We conducted a nested case-control study, recruiting consecutive ibrutinib treated subjects to evaluate cardiovascular risk factors associated with the development of AF in patients diagnosed with hematological B-cell malignancies.Results: Of the 189 patients treated with ibrutinib and without AF at baseline, 54 (29%) developed AF. Cardiovascular risk factors associated with AF development were, older age, prior hypertension (HTN), history of heart failure (HF) and congenital heart disease. A patient with HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 40%, 48%, 64%, and 71%, respectively. Patients with prior HTN without HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 5%, 10%, 23%, and 31%, respectively while on ibrutinib therapy.Conclusions: The relationship between ibrutinib, cardiovascular comorbidities, and AF is through pre-existing cardiovascular disease. An individualized, multidisciplinary approach involving cardiologists should be considered when initiating ibrutinib, particularly when there is a history of HTN, HF or congenital heart disease. In such patients, there should be close cardiovascular monitoring and prompt intervention when AF develops to improve patient outcomes.

Unifying the diagnosis of gestational diabetes mellitus: Introducing the NPRP criteria.

AIMS: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations. METHODS: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM). RESULTS: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years. CONCLUSIONS: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM.

Evaluating the association of frailty with communication about aging-related concerns between older patients with advanced cancer and their oncologists.

BACKGROUND: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. METHODS: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided. RESULTS: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01). CONCLUSIONS: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists. LAY SUMMARY: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists.