bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the representativeness of trial populations for contemporary real-world cancer patients: A case study of adjuvant chemotherapy for colon cancer.
Authors: Lund Jennifer Leigh , Webster-Clark Michael , Bratton Emily W. 
Published: September 2021

306 Background: Randomized controlled trials are the gold standard for assessing the efficacy of new cancer therapies and are required for marketing approval. However, participants enrolled into trials are often not representative of the more diverse populations in whom treatment will ultimately be delivered. Real-world data can be used to potentially bridge this gap by evaluating the effectiveness and safety of therapies in more generalizable populations. In this study, we describe differences in demographic and clinical characteristics between participants enrolled in a phase III trial of adjuvant chemotherapy for colon cancer and a contemporary comparator cohort using structured oncology electronic medical records (EMR) data. Methods: We drew upon publications from the Multicenter International Study of Oxaliplatin/5 Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) recruiting patients primarily from Western Europe with stage II or III colon cancer from October 1998-January 2001. This trial established FOLFOX (oxaliplatin + 5-FU) as the standard of care over 5FU alone in treating stage III colon cancer and led to US marketing approval. For comparison, we identified patients diagnosed with stage II or III colon cancer (September 2014-2020) who received FOLFOX in the IQVIA US Oncology EMR database via E360, IQVIA’s Real World Discovery and Analytics platform. In the two populations, we described distributions of prognostic factors including age, sex, stage of disease, body mass index (BMI), and Eastern Cooperative Group (ECOG) performance status. Results: The MOSAIC trial included 2,246 participants; we identified 4,566 patients starting FOLFOX in the EMR comparator. Median age was similar: 61 versus 62 years, but the range differed (19-75 years versus 18-85 years) in the trial and EMR comparator, respectively. Female sex was similar at 44% and 48%, while the proportion of patients with stage III disease differed considerably at 60% and 84% for trial and EMR comparator, respectively. Half (51%) of all EMR patients were missing ECOG status; among those with a reported ECOG status, 96% had a score of 0-1, while 87% of trial participants had an ECOG of 0-1. BMI was missing in 34% of patients in the EMR comparator; among those with a reported BMI, 28% had a BMI < 25, while 54% of trial participants had a BMI < 25. Conclusions: Colon cancer patients receiving FOLFOX in an EMR comparator had a similar age and sex distribution as MOSAIC trial participants, but were more likely to have stage III disease. Missing ECOG and BMI data were common in the EMR comparator, which limited comparisons. Structured oncology EMR data represent an important resource for generating real-world evidence; future data enrichment efforts focused on critical patient-level variables via unstructured EMR extraction may improve data completeness and quality.
Use of formative evaluation surveying and tailored digital education to identify and address knowledge and competency gaps in upper tract urothelial carcinoma (UTUC) care.
Authors: Ackbarali Tariqa , Turell Wendy , del Nido Elizabeth L. , Shore Neal D. , Pierorazio Phillip M. 
Published: September 2021

307 Background: Upper tract urothelial carcinoma (UTUC) treatment poses a unique challenge for clinicians, due to the complexity in diagnosis, risk stratification, and a lack of treatment options, leading to a lower patient quality of life. However, recent advances in kidney sparing treatment options have created an opportunity for clinicians to integrate newer therapies into practice and improve function for UTUC patients. To address these needs, a serial educational initiative was designed for the uro-oncology team. Methods: A 2-part CE activity was launched in partnership with Large Urology Group Practice Association live-online in June and December, 2020, and remains on-demand through December, 2021 at UroCareLive.com and OMedLive.com. The first activity focused on diagnosis, risk stratification, and newer treatments. Formative evaluation was applied to obtain feedback from the 1st activity through an in-depth survey to clinician learners, the results of which were used to shape the content of the 2nd activity. Formative evaluation survey results revealed gaps in recognizing disease progression (48%), risk stratification (with difficulty obtaining tissue from upper urinary tract noted as the most common barrier; 57%), and experience with newer agents leading to a lack of their use in practice (62%). Only 23% rated their team’s training on patient education as “Very Good” or “Excellent.” Additionally, knowledge and competence questions were administered pre-, immediate post-activity, and at 2-months follow-up. Data from these questions were analyzed to determine engagement and remaining gaps. Results: To date, 788 clinicians participated in the activity. All 8 pre/post-test questions demonstrated statistically significant improvements in knowledge and competence concerning risk stratification, treatment applications, and adverse event management. At 2-mos. follow-up, 75% reported improved behavioral impact on clinical practice and 55% reported impact on patient experience and outcomes. Learners provided write-in examples detailing changes such as improved confidence and understanding of newer treatment options, patient experience, and increased use of kidney-sparing treatments including mitomycin gel. Conclusions: The activity was successful in demonstrating sustained knowledge advances in critical areas such as tumor categorizing and risk stratification, the use of emerging treatment options, and management of adverse events in practice. Use of formative evaluation surveying allowed identification of practice gaps and barriers to change, providing an opportunity for tailored education addressing these needs. Learners also reported strong post-activity improvements in clinical practice and patient outcomes, illustrating the importance of serial education for the uro-oncology team.
Factors associated with failure to receive oral anticancer drugs.
Authors: Doshi Sahil D , Lichtenstein Morgan RL , Beauchemin Melissa Parsons , Raghunathan Rohit R. , Law Cynthia , Accordino Melissa Kate , Wright Jason Dennis , Elkin Elena B. , Hershman Dawn L. 
Published: September 2021

41 Background: Oral anti-cancer drugs (OACDs) have become increasingly prescribed over the last 10 years and require a significant amount of care coordination. Preliminary administrative database studies have shown that 10-15% of prescriptions are never received by the patient, but the reasons behind this are poorly understood. In this study, we prospectively identified failure to receive (FR) cases in which OACD prescriptions were never received by patients, examined underlying reasons for FR, and assessed clinical and process-related factors associated with FR. Methods: We prospectively collected data on new OACD prescriptions for adult oncology patients at a large, urban academic cancer center from 1/1/2018 to 12/31/2019. We collected patient demographic, clinical, and insurance data, OACD delivery date, and interactions with payers and financial assistance groups. FR was defined as failure to receive a prescribed OACD. Reasons for FR were confirmed by manual chart review and classified into seven categories: clinical deterioration, financial access, provider-driven clinical decision making, patient-directed change, transfer of care, lost to follow up, and other. We calculated the relative proportion of each FR category and used multivariable logistic regression to identify factors associated with FR, including initiation of a prior authorization and drug class. Results: The cohort included 1,080 patients who were prescribed 1,269 new OACDs. Of these prescriptions, 13% (N=163) were categorized as FR. Among the 158 patients with FR, average patient age was 66 years, 55% identified as non-Hispanic white, 61% had any Medicare plan, 11% had Medicaid only, and 25% had commercial insurance. Overall, 18% of FR cases were attributed to clinical deterioration, 13% to financial access, 29% to provider-driven clinical decision making, 17% to patient-directed change, 13% to transfer of care, and 5% were lost to follow up. Univariate analysis showed that FR was less likely in cases where prior authorization was initiated (p < 0.001) and multivariate analysis confirmed this result (OR 0.47 [CI 0.33-0.66], p < 0.001). Conclusions: Though the majority of oncology patients prescribed OACDs received the drug, 13% of patients in our study experienced FR. FR is associated with a lack of prior authorization initiation, which may reflect barriers to access, a change in clinical decision-making, or patient choice. Ultimately, FR is multifactorial and may be appropriate in some cases. More work is needed to determine whether improved access would increase uptake in some patients. [Table: see text]
Survival in the real world: A national analysis of patients treated for early-stage breast cancer.
Authors: Franks Jeffrey , Gidwani Risha , Enogela Ene Mercy , Caston Nicole E. , Williams Courtney , Aswani Monica S. , Azuero Andres , Rocque Gabrielle Betty 
Published: September 2021

75 Background: Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is unclear how treatment outcomes may differ for these patients compared to those well represented in trials. Methods: This retrospective cohort study included women diagnosed with early-stage (I-III) breast cancer (EBC) between 2005-2015 in the CancerLinQ Discovery electronic medical record-based dataset. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those aged <45 or ≥70 years were considered underrepresented. Patients who were White and aged 45-69 were considered well represented. Overall and EBC subtype-stratified Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for five-year mortality by representation group. The overall model was adjusted for cancer stage, subtype, chemotherapy intensity, and year of EBC diagnosis. Stratified models were adjusted for cancer stage, individual treatment regimen (due to lack of chemotherapy intensity variation within subtype), and year of EBC diagnosis. Results: Of 11,770 patients, most were aged 45-69 (71%), White (72%), diagnosed with stage II (51%), or HR+HER2- EBC (56%). Unrepresented patients (7%) were categorized due to comorbidities (76%), concurrent cancer (22%), or both (2%). Underrepresented patients (45%) were categorized based on age (44%), race/ethnicity (39%), or both (17%). The remaining patients were well represented in trials (48%). In adjusted models, unrepresented patients had almost three times the hazard of death than well-represented patients (HR 2.71, 95% CI 2.08-3.52; Table). The hazard of death for underrepresented versus well-represented patients was similar (HR 1.19, 95% CI 0.98-1.45). Comparable results were seen in EBC subtype-specific models. Conclusions: Over half of patients in this study would be considered underrepresented or unrepresented in clinical trials due to age, comorbidity, or race/ethnicity. Patients considered unrepresented in trials experienced poorer survival compared to those well-represented. Trialists should ensure study participants reflect the real-world disease population to support evidence-based decision making for all individuals with cancer.[Table: see text]
Exclusion criteria of breast cancer research protocols: A descriptive analysis.
Authors: Wan Clara , Caston Nicole E. , Ingram Stacey A. , Rocque Gabrielle Betty 
Published: September 2021

82 Background: Clinical trials play an important role in advancing cancer treatments. Unfortunately, only about 3% of adults with cancer are enrolled in a clinical trial in the United States due to various barriers to enrollment. This includes restrictive eligibility criteria, which currently have no standard guidelines. The purpose of this study is to evaluate the variability of eligibility criteria. Methods: This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham (UAB) between 2004-2020. Exclusion criteria (e.g., laboratory values and comorbidities) were extracted from protocols using OnCore, an online dataset used to manage clinical trials, and ClinicalTrials.gov. Laboratory values or vital signs analyzed included liver function tests, hematologic labs, Eastern Cooperative Oncology Group (ECOG) performance status, and hypertension. Comorbid conditions included congestive heart failure, cardiovascular disease, presence of central nervous system (CNS) metastases, and history of prior cancer. Comorbid conditions were further analyzed by amount of time protocols required participants to be from initial diagnosis or exacerbation-free. Results: There were a total of 102 eligible protocols. Substantial heterogeneity was observed in exclusion criteria across liver/hematologic laboratory values and demographic/comorbidity variables. Among liver laboratory values, most protocols included an upper limit of acceptable for bilirubin (78%): 9% used the institutional upper limit of normal (ULN), 2% used 1.2xULN, 3% used 1.25xULN, 56% used 1.5xULN, 6% used 2xULN, and 2% used 3xULN. Similar variability was observed in protocols that included alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count: 1% 500mcL, 11% used 1,000mcL, 4% used 1,200mcL, 1% used 1,250mcL, 64% used 1,500mcL, and 1% used 1,800mcL. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%) and a prior cancer (66%). While most protocols included cardiovascular disease, the allowable timeframe varied between protocols: 4% did not allow an acute exacerbation within the previous 3 months, 32% did not allow within the previous 6 months, 5% did not allow within the previous 12 months, and 38 % did not specify a time frame. Protocols including history of a prior cancer as a criterion similarly had varied definitions based on timeline. Conclusions: Substantial heterogeneity was observed among clinical trial protocols. While exclusion criteria are necessary for patient safety, there is lack of evidence for current parameters. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.
Fertility preservation in young breast cancer patients: A population-based study.
Authors: Nguyen Diana , Jamjoum Ghader , Meguerditchian Ari N. 
Published: September 2021

90 Background: Treatment-related infertility is an important cause of distress in young women with breast cancer (YWBC) that is preventable by fertility preservation (FP) prior to initiating therapy. This study assesses FP service use by YWBC in Quebec (Canada). Methods: Administrative claims for women ≤ 40 diagnosed between 01-04-2012 and 31-03-2018 were identified using Quebec’s universal health services database (RAMQ). Access to and use of FP services were ascertained by identifying claims for a visit with an obstetrician/gynecologist (OB/GYN) ≤ 90 days of diagnosis, followed by claims for ovarian stimulation, ovule harvesting or artificial insemination. Patient, disease and treatment-related predictors were estimated using logistic regression. Results: 1 616 YWBC were treated. Mean age was 36 (SD 4.1), 72.1% had a CCI = 0, 84.5% were urban residents, and 72.2% experienced some form of socioeconomical disadvantages. Stage distribution was: 0.93%, 68.8, and 30.3% for stages 0, 1-2, and 3 respectively. 53.0% had a mastectomy, 40.8% received chemotherapy (CT), 70.7% received radiotherapy, 20.9% initiated anti-estrogen therapy. 387 YWBC consulted an OB/GYN within 90 days of diagnosis and 155 subsequently received FP services. Predictors associated with FP use included: decreased age (OR= 0.82, 95CI = 0.79-0.86), type of surgery (OR = 0.46, CI = 0.22-0.97), social isolation (OR =1.39, 95CI = 0.99-1.96) and receipt of chemotherapy (OR = 1.74, 95CI = 1.10-2.76). Conclusions: Only 23.9% of eligible YWBC in Quebec accessed FP specialists. Of these, 40.1% chose to move forward with FP. These findings raise important questions on how to optimize access to FP expertise. [Table: see text]
Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences
Authors: Riestenberg Carrie , Jagasia Anika , Markovic Daniela , Buyalos Richard P , Azziz Ricardo 
Published: September 2021

Abstract

Context
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5% to 20% of women of reproductive age. The economic burden of PCOS was previously estimated at approximately $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, without considering the costs of pregnancy-related and long-term morbidities.

Objective
This study aimed to estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS.

Methods
PubMed, EmBase, and Cochrane Library were searched, and studies were selected in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health, or Androgen Excess and PCOS Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index were included. Two investigators working independently extracted data on study characteristics and outcomes. Data were pooled using random effects meta-analysis. The I2 statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale.

Results
The additional total healthcare-related economic burden of PCOS due to pregnancy-related and long-term morbidities in the United States is estimated to be $4.3 billion annually in 2020 USD.

Conclusion
Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.
PCMD-1 bridges the centrioles and the pericentriolar material scaffold in C. elegans
Authors: Stenzel Lisa , Schreiner Alina , Zuccoli Elisa , Üstüner Sim , Mehler Judith , Zanin Esther , Mikeladze-Dvali Tamara 
Published: September 2021

ABSTRACT
Correct cell division relies on the formation of a bipolar spindle. In animal cells, microtubule nucleation at the spindle poles is facilitated by the pericentriolar material (PCM), which assembles around a pair of centrioles. Although centrioles are essential for PCM assembly, the proteins that anchor the PCM to the centrioles are less known. Here, we investigate the molecular function of PCMD-1 in bridging the PCM and the centrioles in Caenorhabditis elegans. We demonstrate that the centrosomal recruitment of PCMD-1 is dependent on the outer centriolar protein SAS-7. The most C-terminal part of PCMD-1 is sufficient to target it to the centrosome, and the coiled-coil domain promotes its accumulation by facilitating self-interaction. We reveal that PCMD-1 interacts with the PCM scaffold protein SPD-5, the mitotic kinase PLK-1 and the centriolar protein SAS-4. Using an ectopic translocation assay, we show that PCMD-1 can selectively recruit downstream PCM scaffold components to an ectopic location in the cell, indicating that PCMD-1 is able to anchor the PCM scaffold proteins at the centrioles. Our work suggests that PCMD-1 is an essential functional bridge between the centrioles and the PCM.
Dental health status of community-dwelling adults aged 50 years and over in Ireland. A cross-sectional analysis of the Wave 3 TILDA cohort.
Authors: Naseer Amara , McLoughlin Jacinta , Donoghue Orna A. , Kenny Rose Anne , O'Connell Brian 
Published: September 2021

Background: Little is known about the current oral health status of adults in Ireland. The aim of this study was to assess the dental health of community-dwelling adults aged 50 years and over in Ireland and to compare the current status to previous national surveys. Methods: The Irish Longitudinal Study on Ageing (TILDA) Wave 3 assessed the dental health of a subset of participants. Respondents attending for health assessments were offered a dental examination. The World Health Organization examination criteria were used.Results:Of the 3111 people who were offered the dental assessment, 2525 were examined. Adults below 50 years of age and respondents whose dental health data were unavailable at the time of analysis were omitted, giving a final sample of 2504. Among the dental assessment sample, 9.9% (249) were edentate. Of those aged 65 years and older, 15.6% were edentate while for the same age group 40.9% were edentate in the 2000-02 national survey. The mean number of teeth present in those aged 65 years or older was 14.9 for males and 14.2 for females, whereas in 2000-02 it was 9.9 and 7.4, respectively. 56.8% of the dentate sample had 10 or more tooth contacts. The mean DMFT of those aged 50 years or more was 18.5 and the Root Caries Index was 6.3. Between 2000-02 and 2014-5 (this study) in adults aged 65 years and over, the mean DMFT decreased from 25.9 to 20.1 and the Root Caries Index decreased from 11.6 to 9.1.Conclusion: The results indicate improvements in the dental health of community-dwelling adults aged 50 years and over in Ireland as compared to the previous survey of 2000-02. These improvements mean a change in the treatment needs of this age group and will require policy and service adjustments to meet these needs