bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant struma ovarii with thyroid-type papillary and poorly differentiated carcinoma: a case report
Authors: Terayama Nao , Fujiwara Satoe , Ueda Shoko , Yamada Takashi , Ohmichi Masahide
Published: September 2022

Background

Malignant struma ovarii is a very rare type of gynecologic cancer. Although its most common histological subtype is a pure type of papillary thyroid carcinoma containing two components, papillary carcinoma and poorly differentiated carcinoma, malignant struma ovarii is still extremely rare. As a result, the optimal treatment for this type of tumor remains uncertain due to its rarity.

Case presentation

A 62-year-old Japanese female presented with a pelvic tumor and clinical diagnosis of malignant tumor of the ovary. She underwent complete debulking surgery, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The histology of the ovarian tumor revealed malignant struma ovarii with thyroid-type papillary projections and poorly differentiated carcinoma. Because of the complete resection and the absence of distant metastasis, the patient did not receive any adjuvant therapy. At 24 months after surgery, she was free of disease.

Conclusion

This is a rare case report of malignant struma ovarii, without recurrence, in which the component was papillary thyroid carcinoma mixed with poorly differentiated carcinoma. Foregoing adjuvant therapy might be one option for malignant struma ovarii in cases with complete resection and no distant metastasis. In addition, we should consider that long-term follow-up is needed for malignant struma ovarii.
A change of PD-1/PD-L1 expression on peripheral T cell subsets correlates with the different stages of Alzheimer's Disease
Authors: Wu Ching-Tse , Chu Cheng-I , Wang Feng-Yu , Yang Hui-Yu , Tseng Wei-Sung , Chang Chuang-Rung , Chang Chien-Chung
Published: September 2022

Background

Immune checkpoints are a set of costimulatory and inhibitory molecules that maintain self-tolerance and regulate immune homeostasis. The expression of immune checkpoints on T cells in malignancy, chronic inflammation, and neurodegenerative diseases has gained increasing attention.

Results

To characterize immune checkpoints in neurodegenerative diseases, we aimed to examine the expression of the immune checkpoint PD-1/PD-L1 in peripheral T cells in different Alzheimer’s disease (AD) patients. To achieve this aim, sixteen AD patients and sixteen age-matched healthy volunteers were enrolled to analyze their CD3+T cells, CD3+CD56+(neural cell adhesion molecule, NCAM) T cells, CD4+/CD8+T cells, and CD4+/CD8+CD25+(interleukin-2 receptor alpha, IL-2RA) T cells in this study. The expression of PD-1 on T cells was similar between the AD patients and healthy volunteers, but increased expression of PD-L1 on CD3+CD56+T cells (natural killer T cells, NKT-like), CD4+T cells (helper T cells, Th), CD4+CD25+T cells, and CD8+T cells (cytotoxic T lymphocytes, CTL) was detected in the AD patients. In addition, we found negative correlations between the AD patients’ cognitive performance and both CD8+T cells and CD8+CD25+T cells. To identify CD8+T-cell phenotypic and functional characteristic differences between the healthy volunteers and AD patients in different stages, a machine learning algorithm, t-distributed stochastic neighbor embedding (t-SNE), was implemented. Using t-SNE enabled the above high-dimensional data to be visualized and better analyzed. The t-SNE analysis demonstrated that the cellular sizes and densities of PD-1/PD-L1 on CD8+T cells differed among the healthy, mild AD, and moderate AD subjects.

Conclusions

Our results suggest that changes in PD-1/PD-L1-expressing T cells in AD patients’ peripheral blood could be a potential biomarker for monitoring disease and shed light on the AD disease mechanism. Moreover, these findings indicate that PD-1/PD-L1 blockade treatment could be a novel choice to slow AD disease deterioration.
Microscopic marine invertebrates are reservoirs for cryptic and diverse protists and fungi
Authors: Holt Corey C. , Boscaro Vittorio , Van Steenkiste Niels W. L. , Herranz Maria , Mathur Varsha , Irwin Nicholas A. T. , Buckholtz Gracy , Leander Brian S. , Keeling Patrick J.
Published: September 2022

Background

Microbial symbioses in marine invertebrates are commonplace. However, characterizations of invertebrate microbiomes are vastly outnumbered by those of vertebrates. Protists and fungi run the gamut of symbiosis, yet eukaryotic microbiome sequencing is rarely undertaken, with much of the focus on bacteria. To explore the importance of microscopic marine invertebrates as potential symbiont reservoirs, we used a phylogenetic-focused approach to analyze the host-associated eukaryotic microbiomes of 220 animal specimens spanning nine different animal phyla.

Results

Our data expanded the traditional host range of several microbial taxa and identified numerous undescribed lineages. A lack of comparable reference sequences resulted in several cryptic clades within the Apicomplexa and Ciliophora and emphasized the potential for microbial invertebrates to harbor novel protistan and fungal diversity.

Conclusions

Microscopic marine invertebrates, spanning a wide range of animal phyla, host various protist and fungal sequences and may therefore serve as a useful resource in the detection and characterization of undescribed symbioses.
Discrimination, harassment, and intimidation amongst otolaryngology—head and neck surgeons in Canada
Authors: Hamour Amr F. , Chen Tanya , Cottrell Justin , Campisi Paolo , Witterick Ian J. , Chan Yvonne
Published: September 2022

Background

Understanding mistreatment within medicine is an important first step in creating and maintaining a safe and inclusive work environment. The objective of this study was to quantify the prevalence of perceived workplace mistreatment amongst otolaryngology—head and neck surgery (OHNS) faculty and trainees in Canada.

Methods

This national cross-sectional survey was administered to practicing otolaryngologists and residents training in an otolaryngology program in Canada during the 2020–2021 academic year. The prevalence and sources of mistreatment (intimidation, harassment, and discrimination) were ascertained. The availability, awareness, and rate of utilization of institutional resources to address mistreatment were also studied.

Results

The survey was administered to 519 individuals and had an overall response rate of 39.1% (189/519). The respondents included faculty (n = 107; 56.6%) and trainees (n = 82; 43.4%). Mistreatment (intimidation, harassment, or discrimination) was reported in 47.6% of respondents. Of note, harassment was reported at a higher rate in female respondents (57.0%) and White/Caucasian faculty and trainees experienced less discrimination than their non-White colleagues (22.7% vs. 54.5%). The two most common sources of mistreatment were OHNS faculty and patients. Only 14.9% of those experiencing mistreatment sought assistance from institutional resources to address mistreatment. The low utilization rate was primarily attributed to concerns about retribution.

Interpretation

Mistreatment is prevalent amongst Canadian OHNS trainees and faculty. A concerning majority of respondents reporting mistreatment did not access resources due to fear of confidentiality and retribution. Understanding the source and prevalence of mistreatment is the first step to enabling goal-directed initiatives to address this issue and maintain a safe and inclusive working environment.

Graphical Abstract
The impact of hydrothermal alteration on the physiochemical characteristics of reservoir rocks: the case of the Los Humeros geothermal field (Mexico)
Authors: Weydt Leandra M. , Lucci Federico , Lacinska Alicja , Scheuvens Dirk , Carrasco-Núñez Gerardo , Giordano Guido , Rochelle Christopher A. , Schmidt Stefanie , Bär Kristian , Sass Ingo
Published: September 2022

Hydrothermal alteration is a common process in active geothermal systems and can significantly change the physiochemical properties of rocks. To improve reservoir assessment and modeling of high-temperature geothermal resources linked to active volcanic settings, a detailed understanding of the reservoir is needed. The Los Humeros Volcanic Complex, hosting the third largest exploited geothermal field in Mexico, represents a natural laboratory to investigate the impact of hydrothermal processes on the rock properties through andesitic reservoir cores and outcropping analogs. Complementary petrographic and chemical analyses were used to characterize the intensities and facies of hydrothermal alteration. The alteration varies from argillic and propylitic facies characterized by no significant changes of the REE budget indicating an inert behavior to silicic facies and skarn instead showing highly variable REE contents. Unaltered outcrop samples predominantly feature low matrix permeabilities (< 10–17 m2) as well as low to intermediate matrix porosities (< 5–15%), thermal conductivities (0.89–1.49 W m−1 K−1), thermal diffusivities (~ 0.83 10–6 m2 s−1), and sonic wave velocities (VP: ~ 2800–4100 m s−1, VS: ~ 1600–2400 m s−1). Average magnetic susceptibility and specific heat capacity range between 2.4–7.0 10–3 SI and 752–772 J kg−1 K−1, respectively. In contrast, the hydrothermally altered reservoir samples show enhanced porosities (~ 7–23%), permeabilities (10–17–10–14 m2), and thermal properties (> 1.67 W m−1 K−1; > 0.91 10–6 m2 s−1), but a significant loss of magnetic susceptibility (10–3–10–6 SI). In particular, this latter characteristic appears to be a suitable indicator during geophysical survey for the identification of hydrothermalized domains and possible pathways for fluids. The lack of clear trends between alteration facies, alteration intensity, and chemical indices in the studied samples is interpreted as the response to multiple and/or repeated hydrothermal events. Finally, the proposed integrated field-based approach shows the capability to unravel the complexity of geothermal reservoir rocks in active volcanic settings.
Non-prescribed antibiotic use for children at community levels in low- and middle-income countries: a systematic review and meta-analysis
Authors: Edessa Dumessa , Assefa Nega , Dessie Yadeta , Asefa Fekede , Dinsa Girmaye , Oljira Lemessa
Published: September 2022

Background

Non-prescribed antibiotic use is an emerging risky practice around the globe. An inappropriate use involving nonprescription access is one cause of the rapid increase in antibiotic resistance. Children commonly encounter many self-limiting illnesses for which they frequently use antibiotics without prescription. However, no specific and conclusive evidence exists to inform actions against this unsafe practice. We thus aimed to estimate the pooled proportion of non-prescribed antibiotic use for children at community levels in low- and middle-income countries.

Methods

A systematic search of records was conducted from PubMed/Medline, Embase, Scopus, CINAHL, and Google scholar. Eligible English-language publications were original articles which reported on community-based non-prescribed antibiotic use for children and conducted in low- and middle-income countries. Study features and the number of antibiotics used without prescriptions were extracted and pooled for effect sizes employing a random-effects model. The pooled proportion of non-prescribed antibiotic use was estimated as a percentage.

Results

In this analysis, we included a total of 39 articles consisting of 40,450 participants. Of these, 16,315 participants used non-prescribed antibiotics. The pooled percentage for this use of non-prescribed antibiotics was 45% (95% CI: 40–50%). The estimate was considerably higher in studies involving simulated patient methods (56%; 95% CI: 49–62%) than those studies with community surveys (40%; 95% CI: 34–46%) (P = 0.001). It was also varied by the recall period of antibiotics use—56% (95% CI: 50–62%) for instantly observed practice, 36% (95% CI: 22–50%) for within two week recall, 35% (95% CI: 26–45%) for 1–6 months recall, and 46% (95% CI: 37–54%) for more than six months recall (P = 0.001). Primary access points for the non-prescribed antibiotic uses were retail drug outlets.

Conclusions

We found that nearly half of the antibiotics used for children in community settings were without prescriptions. For these unsafe practices, caregivers accessed antibiotics mainly from drug outlets. Hence, context-specific educational and regulatory interventions at these outlets and the community levels are the first steps to improving antibiotic usage for children in low- and middle-income countries.

Trial registration number:CRD42021288971 (PROSPERO). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288971.
Sustainable colorimetric/luminescent sensors enabled by armored lipid nanoparticles
Authors: Roh Jinkyu , Cho Yong Ho , Ahn Dong June
Published: September 2022

In this study, we developed a highly stable polymeric vesicle using a nanosilica-armor membrane to achieve a sustainable colorimetric/luminescent response. The silica armor can be grown directly as ~ 5 nm spherical nanoparticles on the surface of the diacetylene (DA) vesicle with liposomal structure. This can be accomplished via the modified Stöber reaction in pure water on a layer of amine linkers deposited on the vesicles. Once formed, the structural stability of the DA vesicles dramatically increased and remained so even in a dried powder form that could be stored for a period of approximately 6 months. Then, redispersed in water, the armored vesicles did not agglomerate because of the electric charge of the silica armor. After polymerization, the polydiacetylene (PDA) vesicles maintained an average of 87.4% their sensing capabilities compared to unstored vesicles. Furthermore, the silica membrane thickness can be controlled by reiteration of the electrostatic layer-by-layer approach and the direct hydrolysis of silica. As the number of silica armor membranes increases, the passage of the stimuli passing through the membranes becomes longer. Consequently, three layers of silica armor gave the PDA vesicles size-selective recognition to filter out external stimuli. These discoveries are expected to have large-scale effects in the chemo- and biosensor fields by applying protective layers to organic nanomaterials.

Graphical Abstract
Differences in Physical Match Performance and Injury Occurrence Before and After the COVID-19 Break in Professional European Soccer Leagues: A Systematic Review
Authors: Thron Maximiliane , Düking Peter , Härtel Sascha , Woll Alexander , Altmann Stefan
Published: September 2022

Background

Due to the COVID-19 pandemic, matches and soccer-specific training were suspended for several weeks, matches after resumption were congested, and substitutions per team and game increased from three to five.

Objective

The aim of this review was to examine possible differences in physical match performance and injuries between before and after the COVID-19 induced break of matches and training in professional male European soccer leagues during the 2019/2020 season.

Methods

A systematic search identified all scientifically peer-reviewed publications involving elite male soccer players competing in the European leagues which reported physical match performance variables such as total running distance and running distance at different speed zones and/or injury parameters pre- and post-COVID-19 induced break.

Results

In total, 11 articles were included, which were coming from German Bundesliga, Polish Ekstraklasa, Croatian HNL, Spanish La Liga, and Italian Serie A. In all studies investigating the German Bundesliga, most parameters of physical match performance remained unaffected (0.08 ≤ p ≤ 0.82; − 0.15 ≤ ES 0.15), while studies investigating the Polish Ekstraklasa (p ≤ 0.03; − 0.27 ≤ ES − 0.18), Croatian HNL (p ≤ 0.04; − 1.42 ≤ ES ≤ 1.44), Spanish La Liga (p ≤ 0.017; − 0.32 ≤ ES ≤ 5.5), and Italian Serie A (p ≤ 0.014; − 1.01 ≤ ES 0.24) showed a decrease in most parameters of physical match performance after the COVID-19 break. Injury rates were only investigated by studies targeting the German Bundesliga and Italian Serie A. In the majority of studies (3 out of 4 studies), there occurred no difference in injuries between pre- and post-COVID-19 break (p > 0.05; ES = N/A).

Conclusion

Results indicate that Bundesliga teams maintained physical match performance during the 9-weeks break in matches and 3-weeks break in group training, whereas a longer match and group training interruption up to 15 weeks and 8 weeks, respectively, in the other leagues appeared to lead to a decreased physical match performance. Regarding injuries, we speculate that the increase in substitutions from 3 to 5 substitutions per game might prevent an increase in injury occurrence during matches. The underlying studies’ results provide hints for possible upcoming unexpected interruptions with respect to optimal physical preparations for the resumption of matches and a congested schedule to maintain physical match performance, or for possible rule changes such as 5 instead of 3 substitutions to avoid physical overload during congested match schedules.
Risk factors for epiretinal membrane formation and peeling following pars plana vitrectomy for primary rhegmatogenous retinal detachment, an OCT guided analysis
Authors: Szigiato Andrei-Alexandru , Antaki Fares , Javidi Simon , Touma Samir , Duval Renaud , Cordahi Ghassan , Olivier Sebastien , Rezende Flavio A.
Published: September 2022

Background

To evaluate the rate and risk factors of epiretinal membrane (ERM) formation and need for ERM peeling after pars plana vitrectomy (PPV) for uncomplicated primary rhegmatogenous retinal detachment (RRD).

Methods

Retrospective, single-center, cohort study of 119 consecutive patients (119 eyes) that underwent RRD repair using PPV. The primary outcomes were ERM formation, classified using an optical coherence tomography grading system, and the rate of ERM peeling. Visual acuity, postoperative complications, and risk factors for ERM formation and peeling were also identified.

Results

Postoperative ERM formation occurred in 69 eyes (58.0%); 56 (47.1%) were stage 1, 9 (7.6%) stage 2, 3 (2.5%) stage 3, and 1 (0.8%) stage 4. Only 6 (5.0%) eyes required secondary PPV for a visually significant ERM, with a mean time to reoperation of 488 ± 351 days. Risk factors for ERM formation included intraoperative cryotherapy, more than 1000 laser shots, 360° laser photocoagulation, and choroidal detachment (p < 0.01). Eyes with more than 3 tears had a trend towards increased ERM surgery (p = 0.10).

Conclusions

Visually significant ERM formation following PPV for primary RRD was uncommon in this cohort (5%). Half of the ERMs were detected after the first post-operative year, indicating that this complication may be underreported in studies with only 1-year follow-up.
Aortic valve calcium volume as measured by native versus contrast-enhanced computer tomography and the implications for the diagnosis of severe aortic stenosis in TAVR patients with low-gradient aortic stenosis
Authors: El Garhy Mohammad , Owais Tamer , Lauten Philipp
Published: September 2022

Background

Most of TAVR centers evaluate the calcium score in contrast-enhanced (ce) CT. We compared in this study between different methodologies to measure calcium score. We studied also the difference between patients with low-gradient (LG) and high-gradient (HG) severe aortic stenosis (AS) as regard the burden of aortic valve calcium (AVC).

Results

We measured the calcium volume and score using Agatston methodology in non-contrast (nc) CT and with modified and fixed 850 Hounsfield unit (HU) thresholds in ce CT. The calcium score and volume in ceCT using even with modified thresholds is significantly lower than the assessed score and volume in ncCT. The median (IQR) of calcium score in nc CT and in cc CT were 1288 AU (750–1815) versus 947 HU (384–2202). The median (IQR) of calcium volume in nc CT and in cc CT with modified thresholds were 701 mm3 (239–1632) versus 197 mm3 (139–532). Agatston score and calcium volume were lower in patients with LG AS than HG AS; 2069 AU (899–2477) versus 928AU (572–1284) and 1537 mm3 (644–1860) versus 286 mm3 (160–700), respectively. Only 20% of patients with LGAS had Agatston score higher than the previously supposed AVC score threshold for the diagnosis of severe AS (> 2000AU in men and > 1200 in women).

Conclusions

The diagnosis of severe LGAS should not depend on a single parameter as calcium score. In these patients, calcium score should be measured in nc CT and not in ce CT.
Complex post-traumatic stress disorder: a much needed diagnosis
Authors: Cloitre Marylene
Published: September 2022

This commentary conveys appreciation for a recent review of the rates of complex post-traumatic stress disorder (CPTSD) among refugees, describes the relevance of CPTSD to the refugee experience and discusses implications for assessment and treatment, the effective development of which requires collaboration among researchers, clinicians and individuals with lived experience.
Design and Evaluation of a Computational Phenotype to Identify Patients With Metastatic Breast Cancer Within the Electronic Health Record
Authors: Neely Benjamin , Shahsahebi Mohammad , Marks Caitlin E. , Power Steve , Kanter Andrew , Howell Claire , Hyslop Terry , Plichta Jennifer K.
Published: September 2022

PURPOSE

Outcomes for patients with metastatic breast cancer (MBC) are continually improving as more effective treatments become available. Granular data sets of this unique population are lacking, and the standard method for data collection relies largely on chart review. Therefore, using electronic health records (EHR) collected at a tertiary hospital system, we developed and evaluated a computational phenotype designed to identify all patients with MBC, and we compared the effectiveness of this algorithm against the gold standard, clinical chart review.

METHODS

A cohort of patients with breast cancer were identified according to International Classification of Diseases codes, the institutional tumor registry, and SNOMED codes. Chart review was performed to determine whether distant metastases had occurred. We developed a computational phenotype, on the basis of SNOMED concept IDs, which was applied to the EHR to identify patients with MBC. Contingency tables were used to aggregate and compare results.

RESULTS

A total of 1,741 patients with breast cancer were identified using data from International Classification of Diseases codes, the tumor registry, and/or SNOMED concept identifiers. Chart review of all patients classified each patient as having MBC (n = 416; 23.9%) versus not (n = 1,325; 75.9%). The final computational phenotype successfully classified 1,646 patients (95% accuracy; 82% sensitivity; 99% specificity).

CONCLUSION

Hospital systems with robust EHRs and reliable mapping to SNOMED have the ability to use standard codes to derive computational phenotypes. These algorithms perform reasonably well and have the added ability to be run at disparate health care facilities. Better tooling to navigate the polyhierarchical structure of SNOMED ontology could yield better-performing computational phenotypes.
Development and Adaptation of a Patient-Centered Communication Survey for Parents of Children With Cancer in Guatemala
Authors: Graetz Dylan E. , Rivas Silvia Elena , Fuentes Ana Lucia , Caceres-Serrano Annie , Antillon-Klussmann Federico , Rodriguez-Galindo Carlos , Mack Jennifer W.
Published: September 2022

PURPOSE

Surveys to assess patient and family experiences of pediatric cancer care have been primarily developed and validated in high-income Western settings with English-speaking participants. However, 90% of children with cancer live in low- and middle-income countries. We sought to develop a survey focused on pediatric cancer communication for use in a low-literacy population in Guatemala, including adaptation of many previously validated items.

METHODS

A multidisciplinary team developed a quantitative survey on the basis of a theoretical model of important components and influences on pediatric cancer communication. The original survey included established items previously used in high-income settings and novel questions designed for this study. The survey was translated into Spanish and pilot tested with parents of children receiving treatment at Unidad Nacional de Oncologia Pediatrica in Guatemala City, Guatemala, from April-June 2019. Cognitive interviews were used during pilot testing, and the survey was iteratively revised throughout this process.

RESULTS

Early in testing, Guatemalan parents tended to choose answers at the extreme ends of response categories and socially desirable responses. Ultimately, a visual aid was developed to accompany three-item Likert scale response options. This allowed for successful administration of the survey instrument, resulting in moderate variation of response options and similar proportions to those generated when the original five-item responses were used in parent populations from the United States.

CONCLUSION

Appropriately adapted surveys are necessary to understand patient-centered communication among pediatric oncology populations in low- and middle-income countries. Eventual validation of such tools will enable cross-cultural studies and comparative analysis of results.
Oncology-hospitalist co-management: A model for efficient, high-quality care and education.
Authors: Morris Jensa Catherine , Prsic Elizabeth Horn , Parker Nathaniel , Weber Urs , Gombos Erin Ann , Kottarathara Mathew , Gould Rothberg Bonnie Elyssa , Adelson Kerin B.
Published: September 2022

1

Background: Our inpatient oncology service at Smilow Cancer Hospital had long lengths of stay, high readmission rates and burnout among outpatient oncologists who rotated as inpatient attendings. With a proposal to improve length of stay by.25 days in the first year, the health system funded the integration of internal medicine hospitalists. Methods: Patients were randomly assigned to one of two oncology teams, allowing for real time outcome comparisons. Hospitalists were added to the Intervention Team and served as the primary attending with oncologists as consultants; Oncologists served as the primary attending on the Traditional Team. The intervention began in July 2021. Outcome metrics included LOS, readmission rate, case volume, early discharge rate, educational rankings, and oncologist satisfaction. A multidisciplinary steering group met to review data, study, and act on outcome metrics. Using Quality Improvement PDSA cycles, outcomes were reported at 3 months (PDSA 1), followed by improvement interventions; then reported again at 6 months (PDSA 2). Results: The Intervention Team achieved a 1.0-day reduction in LOS compared to Traditional team. There was no difference in Severity of Illness score in comparator groups, demonstrating no imbalance in patient population. The Intervention team cared for a 29% higher volume of patients and improved early discharge rate without an increase in readmissions from baseline. Oncologists reported a high level of satisfaction with the program. Housestaff overall educational rankings increased after the introduction of hospitalists (Table). Discussion: Hospitalist comanagement exceeded business plan LOS reduction target without compromise in quality or educational metrics. PDSA 1 identified need for role clarity among physicians, increased oncology teaching, and preservation of resident autonomy; PDSA 2 identified need for increased nursing-physician collaboration. Conclusions: Hospitalist comanagement can effectively reduce oncology LOS without adverse effect on readmission rates, educational outcomes, or oncologist satisfaction with care.[Table: see text]
Evaluating the effect of a scalable cancer-navigation program on total cost of care.
Authors: Worland Scott Campbell , Albin Margot , Dorsey Brian , Fosnocht Kevin , Gomez Juan , Johnstone Denise , Kirayoglu Alphan , Licitra Edward , Parikh Ravi Bharat , Sachdeva Kush , Thompson Keith , Voigt Scott , Woerner Shannon , Green Robert Jeffrey
Published: September 2022

4

Background: Cancer-patient navigation programs have been shown to reduce total cost of care while improving outcomes. Previous research has focused on navigation programs embedded within a single institution or a single network of practices. We explore whether an independent cancer-patient navigation program deployed in collaboration with a Medicare Advantage (MA) plan can demonstrate similar cost savings when deployed across a wide variety of practice settings in the state of New Jersey. Methods: We conducted a retrospective observational study to determine the per member per month (PMPM) total cost of care (TCOC) difference between cancer patients with and without a navigation intervention provided by Thyme Care, a technology-enabled virtual cancer-navigation platform. The team, staffed by both lay-health workers and nurses, was assigned members of a single MA plan’s population in NJ beginning on March 2, 2021. Patients with a cancer-specific ICD-10 code who received systemic antineoplastic therapy were eligible for the program. The navigation team coordinated care, addressed barriers to care, facilitated goals of care discussions, and conducted proactive and reactive symptom assessment. The cadence of the symptom assessment was determined by both patient and disease-specific criteria. Concerning responses were triaged to the patient’s oncology team the same day. The study period was from January 1, 2018 to June 13, 2022. The primary outcome was TCOC excluding part D drug spend. We compared TCOC for patients who received the intervention to a control group of eligible individuals that were matched using propensity scores derived from clinical and demographic covariates. We used a repeated measure generalized linear model to estimate the monthly effect of navigation on TCOC. Additionally, we conducted a monte-carlo sensitivity analysis to provide an upper and lower bound on the cost savings. Results: Of 4,172 eligible members, 662 were in the treatment group (across 25 community practices and 45 hospital based practices) and 3,510 were in the control group (across 58 community practices and 73 hospitals). The propensity matching resulted in 188 members in both the treatment and the control group (376 total). The mean TCOC declined $459 more PMPM for the navigated group compared to the non-navigated group. The sensitivity analysis suggested a plausible range of $209-708 PMPM savings in the intervention group. Conclusions: This is the first study to demonstrate that a cancer-navigation program can reduce overall costs when deployed in collaboration with a health plan across a wide geography and range of practice types.
Health care costs among men with metastatic castration-resistant prostate cancer (mCRPC) in the U.S. Medicare population.
Authors: Freedland Stephen J. , Davis Matthew , Epstein Andrew J. , Arondekar Bhakti , Ivanova Jasmina I.
Published: September 2022

10

Background: Studies have reported healthcare costs before and after mCRPC diagnosis in commercially insured populations, but no information is available about costs with progression through lines of therapy after mCRPC diagnosis. This study describes healthcare costs among men with mCRPC in the US Medicare population before mCRPC diagnosis, after diagnosis, and with progression through lines of therapy. Methods: Men newly diagnosed with mCRPC were identified in Medicare fee-for-service claims during 1/1/2014–6/30/2019. Adult men were required to have a diagnosis of prostate cancer, metastasis diagnosis, castration-resistance using a published claims-based algorithm, and continuous insurance coverage for ≥1 year before and ≥6 months after index mCRPC diagnosis unless patients died. Unadjusted all-cause healthcare costs (medical and pharmacy) per patient per year (PPPY) to Medicare inflated to 2019 dollars were described for the periods before mCRPC diagnosis, after diagnosis, and from the start of first-line (1L), second-line (2L), and third-line (3L) therapy with mCRPC life-prolonging treatments to the start of subsequent therapy or end of follow up. Results: Among 14,780 men with mCRPC, median age was 75 years, and the mean Quan-Charlson Comorbidity Index was 2.1. Median follow-up after mCRPC diagnosis was 17 months. During the follow up, 3,252 men had no life-prolonging treatment, 11,528 men initiated 1L mCRPC therapy, 6,275 initiated 2L, and 2,945 initiated 3L. Mean all-cause healthcare costs PPPY were $27,468 in the year before mCRPC diagnosis, $124,379 after mCRPC diagnosis, $102,380 among men without life-prolonging treatment after mCRPC diagnosis, $148,325 from the start of 1L to subsequent therapy or end of follow up, $160,118 from the start of 2L therapy, and $165,186 from the start of 3L therapy. Conclusions: Mean healthcare costs increased over 4-fold from before to after mCRPC diagnosis and increased steadily as patients progressed from first through third lines of mCRPC therapy. These findings help quantify the economic burden of mCRPC and contextualize the economic value of treatments that delay disease progression.[Table: see text]
Low-risk episode characteristics with an impact on total cost of care and performance in the Oncology Care Model.
Authors: Indurlal Puneeth , Garey Jody S. , Hoverman John Russell , Mills Lydia , Payne-De Bock Judi , Staggs Stuart , Wilfong Lalan S.
Published: September 2022

12

Background: The Oncology Care Model (OCM) is an episode-based, Medicare value-based care program, that rewards providers for decreasing the total cost of care (TCOC) compared to a benchmark price. The model differentiates breast & prostate cancer treated with hormone-only therapy, and bladder cancer treated with Bacillus Calmette-Guérin and/or mitomycin as low-risk episodes (LRE). All other qualifying cancers, including breast, prostate & bladder cancer treated with chemotherapy are designated as high-risk episodes (HRE). Independent evaluation of OCM Performance Periods (PP) 1-6 suggests that reductions in TCOC predominantly occurred in HRE but were offset by increased TCOC in LRE. We seek to evaluate the episode characteristics that have a bearing on LRE performance in OCM. Methods: Episode claims data for 14 practices in The US Oncology Network (The Network) participating in OCM during PP 1-6 were assessed. Several episode characteristics including patient age, gender, comorbidities, cancer type, oncology touchpoints, etc. were evaluated. Results: LRE accounted for 30.5% of total episodes for The Network in OCM from PP1-6, with average benchmark price of $6,700. 85% of LRE were breast cancer patients with average benchmark of $5,800. Only 30% of LRE had increased TCOC exceeding benchmark. Average TCOC increased gradually with increasing age, with highest TCOC at extremes of patient age (18-64 and 80+). Episodes with multiple comorbidities (defined as Hierarchical Condition Category (HCC) flags 3, 4-5, 6+) had an average TCOC 3-times higher than episodes with fewer-or-no comorbidities (HCC flags 0, 1, 2). Episode expenses beyond cancer care (inpatient, nursing facility, home health, long term care, durable medical equipment, and inpatient rehabilitation) were 2.5 times higher for patients with advancing age (75-79 or 80+) and multiple comorbidities. Additionally, these patients had lower physician services expenses, fewer oncology care touchpoints (defined as visits with the Oncology practice), and a four-fold higher death rate. Conclusions: In the OCM, LRE for older patients with multiple comorbidities had higher TCOC, with fewer oncology touchpoints, higher death rates, and episode expenses beyond cancer care contributing the most to TCOC. Incorporating a comprehensive geriatric assessment (composed of physical, functional, cognitive, mental, and socioenvironmental factors) could guide oncologic therapeutic choices, and appropriate clinical management of these patients to improve outcomes. In addition, a modified, resource utilization-based risk adjustment approach could better fit this population.
Real-world treatment (tx) patterns, cost, and overall survival (OS) by line of therapy among patients (pt) with mantle cell lymphoma (MCL): A SEER-Medicare (SM) analysis.
Authors: Keating Scott J. , Rege Sanika , McBride Ali , Shah Ruchit , Qian Joyce , Chirikov Viktor
Published: September 2022

19

Background: MCL is an aggressive form of non-Hodgkin’s lymphoma with an incidence of 1 in 200,000 in the United States. Limited evidence exists on real-world tx utilization, costs, and survival outcomes associated with MCL among older pts in the US. This study examined tx patterns and quantified cost and OS in first- (1L), second- (2L), and third-line (3L) settings in SM pts with MCL. Methods: This retrospective cohort study included older pts (age ≥ 66 yrs) with MCL, identified using a SM-linked database from 01/01/2013 to 12/31/2017, and followed for 2 yrs. Pts were eligible if they had ≥ 1L MCL tx with ≥ 6 months (mo) of continuous enrollment before and after MCL diagnosis. Pts with other primary malignancies or stem cell transplantation (SCT) ≤ 6 mo before first diagnosis of MCL were excluded. A tx regimen was defined as combination of all agents ≤ 35 days of tx initiation; rituximab (R) monotherapy initiated ≤ 7 mo after R-containing regimen was considered maintenance. For each tx line, all-cause and MCL-specific health care resource utilization (HCRU) and costs were calculated per pt per year (PPPY) and adjusted to 2021 US dollars. Kaplan‒Meier method for survival analysis was used to estimate OS in 1L, 2L, and 3L settings. Results: This study included 559 pts with newly diagnosed MCL: median (range) age, 75 (66‒94) yrs; male, 59.7%; mean Charlson Comorbidity Index, 1.44; stage IV (45.3%), and poor performance status (12.2%); subsequently, 305 (54.6%) received 2L and 153 (27.4%) received 3L tx. The most common regimens were bendamustine + R (51.7%) in 1L and ibrutinib in 2L (17%) and 3L (15.7%). For 1L, 2L, and 3L, 6.3%, 14.8%, and 8.5% of pts received radiation therapy, and 0.4%, 5.1%, and 8.6% received SCT, respectively. Median time to next treatment from start of previous line was 245, 127, and 222 days for 1L to 2L, 2L to 3L, and 3L to 4L, respectively. Mean (SD) all-cause total (medical + drug) costs were $169,210 ($174,904), $209,092 ($254,229), and $185,718 ($220,495) PPPY. The median OS from MCL diagnosis until end of follow-up was 47.2 mo (95% CI, 40.9‒53.7). The 12-mo survival was 81.1% (95% CI, 77.5%‒84.9%), 71.4% (95% CI, 65.5%‒77.9%), and 69.9% (95% CI, 61.8%‒79.1%) for 1L, 2L, and 3L, respectively. Conclusions: The study results report substantial costs associated with the use of standard care therapies among older pts with MCL. New treatments are needed to improve clinical outcomes, and reduce HCRU and overall healthcare costs in MCL.
Estimating prevalence and financial impact of “bagging” oncology drugs: Evidence from privately-insured patients with cancer.
Authors: Shih Ya-Chen Tina , Xu Ying
Published: September 2022

25

Background: “Bagging” is a drug delivery model that distributes physician-administered drugs through pharmacies, most specialty pharmacies. Under the traditional buy-in-bill model oncology drugs are covered in medical benefit, whereas drugs distributed through bagging practices are reimbursed under pharmacy benefit. Several professional associations have urged policymakers to limit or prohibit bagging practices, citing patient safety as the main concern. This study estimated the prevalence of bagging practice and the associated financial impact among cancer patients with private insurance. Methods: We selected 10 cancer drugs with highest total spending from the 2020 Medicare Part B Drug Spending Dashboard. Using 2019-2020 MarketScan data, we identified these drugs from medical and/or pharmacy claims and estimated the prevalence of “bagging” practice as the proportion of patients who had their cancer drugs covered by pharmacy benefit. We compared the per patient per month (PPPM) insurance payment and out-of-pocket expense (OOPE) between medical and pharmacy claims and tested the difference in PPPM costs using non-parametric Wilcoxon test. Results: The top 10 drugs selected for this study included four immunotherapy (pembrolizumab, nivolumab, durvalumab, atezolizumab), five targeted therapy drugs (rituximab, bevacizumab, daratumumab, trastuzumab, pemetrexed), and one supportive care product (pegfilgrastim). The study cohort consisted of 39,757 cancer patients, including 10,599, 19,276, and 17,882 patients (not mutually exclusive) receiving immunotherapy, targeted therapy agents, and supportive care drug, respectively. On average, “bagging” practice was observed in 4.4% of patients, ranging from less than 1% for immunotherapy and 2.4% for targeted therapy to 6.9% for supportive care drugs. The prevalence of bagging practice was higher in comprehensive plans (11.3%) and PPO (4.3%) versus other insurance plan types (3.8%). By census region, the prevalence was highest in Northeast (7.2%) and lowest in North Central (3.4%). Insurance payment PPPM was lower for drugs distributed through bagging practices than the conventional buy-and-bill model (mean $11,075 vs. $13,622; median $9,275 vs. $10,728, P < 0.001). OOPE PPPM exhibited the opposite pattern, with mean and median OPPE $437 and $53 for bagging practices and $186 and $0 for buy-and-bill. Conclusions: We observed wide variation in bagging practices by drug classes, plan types, and geographic regions. Evidence from the privately insured suggested that although bagging oncology drugs appeared to have reduce oncology drug costs for payors, this practice was associated with higher OOP for cancer patients with private insurance. Future research should examine the impact of bagging practices on clinical outcomes, such as treatment delays or disruptions and treatment-related side effects.
Determinants of low-value imaging for patients with low-to-intermediate risk microscopic hematuria.
Authors: Birken Sarah A , Peluso Alexandra , Wagi Cheyenne , Bundy Richa , Witek Lauren , Krol Bridget C. , Pathak Ram , Nielsen Matthew E. , Matulewicz Richard , Parchman Michael L. , Dharod Ajay
Published: September 2022

27

Background: In the US, two million people are referred to urologists for the evaluation of microscopic hematuria (MH). MH guidelines were revised in 2020 by the American Urological Association, recommending that only patients at high risk for malignancy based on age, smoking history, or urinalysis receive computed tomography (CT) imaging. We found in previous studies that providers continued to use CT for patients with low-to-intermediate risk, representing low-value care. To understand reasons for continued CT use for patients with low-to-intermediate risk MH, we assessed determinants of low-value care in a concurrent mixed-method study. Methods: We stratified patients with a urology consultation within 180 days of a urinalysis documented in one academic medical center’s electronic health record between 1/1/15 and 7/1/21 into high-, intermediate-, and low-risk categories and validated risk designation in a chart review of a 5% subsample. We defined low-value care as CT for patients with low-to-intermediate-risk MH. To assess determinants of low-value MH care, we conducted semi-structured interviews with primary, urology, and gynecology providers (n = 7) identified through our professional networks. Results: Six hundred nineteen patients were referred to urology for MH. 58.6% were high-risk, 33.6% intermediate-risk, 4.4% low-risk, and 3.4% were undefined. 15.9% of intermediate-risk (n = 33) and 11.1% of low-risk (n = 3) patients received CT. Of the 14 patients referred to urology post-guideline change, none with low-to-intermediate-risk received CT. Interviews demonstrated substantial variation in approaches to MH evaluation. Urologists were largely aware of the revised guideline but noted inappropriate evaluation before referral, unnecessary referrals, and inefficiency in evaluation following referral. Lacking accessible data for risk stratification, other providers’ approaches were varied but driven by a common goal of ruling out renal malignancy, based on medical school training and institutional norms. Conclusions: Low-value care was limited but persistent and may be driven by a lack of resources to support risk-stratified MH evaluation, including accessible risk stratification data and clear guidelines for appropriate evaluation. This is consistent with a lack of practical guidance for implementing MH evaluation guidelines. In future studies, we will develop strategies to facilitate risk-stratified MH evaluation in practice.
Comparing chair time required for systemic agent drug reaction (DR) management to allocated chair time for systemic protocol.
Authors: Rauw Jennifer Marie , Anderson Helen , Parimi Sunil , Brown Michelle , Hennessy Kathleen
Published: September 2022

40

Background: Chemotherapy scheduling and determining associated nursing resources are complex multiobjective decision problems. Management of DRs are thought to take additional chair and nurse time and should be accounted for in appointment scheduling in order to having an efficiently running clinic. BC Cancer – Victoria is a tertiary care regional site of BC Cancer in Victoria, British Columbia, Canada and currently schedules patients using a regimen-based resource intensity model (Greene et al, 2012). Methods: DRs were tracked in real time over 3 months, where BC Cancer ID, reaction, protocol, agent, cycle number and time of reaction were recorded. Our electronic medical record was interrogated to determine start and end of chair time. We then compared the actual chair time required to manage patients with a DR to scheduled chair time. Results: Thirty reactions occurred, including DRs to paclitaxel (43%), rituximab (13%), docetaxel (10%), nivolumab (7%), oxaliplatin (7%), pertuzumab (7%), bendmustine (3%), and daratumumab (3%). The reactions most commonly occurred with cycles 1 or 2. The averages for total chair time during DR, time from arrival to reaction, and time from reaction to discharge were 281 min (+79.5), 106 min (+ 55), and 171 min (+ 94), respectively. An average of 449 min/month extra were required for DR management above scheduled chair time. Conclusions: The agents precipitating DRs were common and predictable. An average of 7 hours and 29 minutes per month above scheduled chair time was required to manage DRs. This information could be used to more efficiently schedule chair and nursing time. This also highlights the need to minimize the number of DRs as management is resource intensive.[Table: see text]
Carbon emissions and non-biodegradable medical waste generation with alternative dosing strategies.
Authors: Jacobson Sofia I , Kacew Alec , Knoebel Randall W. , Hsieh Po-Hung , Ratain Mark J. , Strohbehn Garth William
Published: September 2022

44

Background: Climate change from human activity results in catastrophic environmental effects that endanger human life. Health care is responsible for ̃10% of greenhouse gas emissions in the United States, thus health systems are pursuing net-zero emissions care. Methods: This single-center, retrospective, case-control study evaluated the environmental impact of alternative trastuzumab, specifically reducing adjuvant therapy duration from 12 to 6 months (in line with clinical trial evidence) and changing administration frequency from every 3 to every 4 weeks (based on pharmacokinetic simulation). Carbon emissions were estimated from round-trip travel distances, and non-biodegradable waste was estimated by collecting and weighing all single-use items used in trastuzumab preparation and administration. We generated population estimates using SEER data. Results: We identified 192 patients with HER2+ breast cancer who received trastuzumab between 2017 and 2019. At a population level, the environmental impact of continued standard-of-care dosing was 22,919 kg of waste and 1,077,210 kg of carbon emissions, requiring ̃49,000 trees to offset. 12 versus 6 months adjuvant treatment duration led to larger expected environmental benefits: 50,536 kg of waste and 3,265,039 kg of carbon emissions could be avoided with universal adoption of 6-month adjuvant therapy. Conclusions: Given health care's increasing emphasis on net-zero care, clinical trials and use of pharmcokinetically equivalent alternative dosing strategies can in part justified by environmental benefits.[Table: see text][Table: see text]