Risk factors for financial toxicity in patients with gynecologic cancer.

BACKGROUND: The cost of cancer care is high and rising. Evidence of increased patient cost burden is prevalent in the medical literature and has been defined as "financial toxicity," the financial hardship and financial concerns experienced by patients because of a disease and its related treatments. With targeted therapies and growing out-of-pocket costs, patient financial toxicity is a growing concern among patients with gynecologic cancer. OBJECTIVE: This study aimed to determine the prevalence of financial toxicity and identify its risk factors in patients with gynecologic cancer treated at a large cancer center using objective data. STUDY DESIGN: Using institutional databases, we identified patients with gynecologic cancer treated from January 2016 to December 2018. Patients with a preinvasive disease were excluded. Financial toxicity was defined according to institutionally derived metrics as the presence of ≥1 of the following: ≥2 bills sent to collections, application or granting of a payment plan, settlement, bankruptcy, financial assistance program enrollment, or a finance-related social work visit. Clinical characteristics were gathered using a 2-year look-back from the time of the first financial toxicity event or a randomly selected treatment date for those not experiencing toxicity. Risk factors were assessed using chi-squared tests. All significant variables on univariate analysis were included in the logistic regression model. RESULTS: Of the 4655 patients included in the analysis, 1155 (25%) experienced financial toxicity. In the univariate analysis, cervical cancer (35%), stage 3 or 4 disease (24% and 30%, respectively), younger age (35% for age <30 years), nonpartnered marital status (31%), Black (45%) or Hispanic (37%) race and ethnicity, self-pay (48%) or commercial insurance (30%), clinical trial participation (31%), more imaging studies (39% for ≥9), ≥1 emergency department visit (36%), longer inpatient stays (36% for ≥20 days), and more outpatient clinician visits (41% for ≥20 visits) were significantly associated with financial toxicity (P<.01). In multivariate analysis, younger age, nonpartnered marital status, Black and Hispanic race and ethnicity, commercial insurance, more imaging studies, and more outpatient physician visits were significantly associated with financial toxicity. CONCLUSION: Financial toxicity is an increasing problem for patients with gynecologic cancer. Our analysis, using objective measures of financial toxicity, has suggested that demographic factors and healthcare utilization metrics may be used to proactively identify at-risk patients for financial toxicity.

3D Printed Multiphasic Scaffolds for Osteochondral Repair: Challenges and Opportunities.

Osteochondral (OC) defects are debilitating joint injuries characterized by the loss of full thickness articular cartilage along with the underlying calcified cartilage through to the subchondral bone. While current surgical treatments can provide some relief from pain, none can fully repair all the components of the OC unit and restore its native function. Engineering OC tissue is challenging due to the presence of the three distinct tissue regions. Recent advances in additive manufacturing provide unprecedented control over the internal microstructure of bioscaffolds, the patterning of growth factors and the encapsulation of potentially regenerative cells. These developments are ushering in a new paradigm of 'multiphasic' scaffold designs in which the optimal micro-environment for each tissue region is individually crafted. Although the adoption of these techniques provides new opportunities in OC research, it also introduces challenges, such as creating tissue interfaces, integrating multiple fabrication techniques and co-culturing different cells within the same construct. This review captures the considerations and capabilities in developing 3D printed OC scaffolds, including materials, fabrication techniques, mechanical function, biological components and design.

Negative Printing for the Reinforcement of In Situ Tissue-Engineered Cartilage.

In the realm of in situ cartilage engineering, the targeted delivery of both cells and hydrogel materials to the site of a defect serves to directly stimulate chondral repair. Although the in situ application of stem cell-laden soft hydrogels to tissue defects holds great promise for cartilage regeneration, a significant challenge lies in overcoming the inherent limitation of these soft hydrogels, which must attain mechanical properties akin to the native tissue to withstand physiological loading. We therefore developed a system where a gelatin methacryloyl hydrogel laden with human adipose-derived mesenchymal stem cells is combined with a secondary structure to provide bulk mechanical reinforcement. In this study, we used the negative embodied sacrificial template 3D printing technique to generate eight different lattice-based reinforcement structures made of polycaprolactone, which ranged in porosity from 80% to 90% with stiffnesses from 28 ± 5 kPa to 2853 ± 236 kPa. The most promising of these designs, the hex prism edge, was combined with the cellular hydrogel and retained a stable stiffness over 41 days of chondrogenic differentiation. There was no significant difference between the hydrogel-only and hydrogel scaffold group in the sulfated glycosaminoglycan production (340.46 ± 13.32 µg and 338.92 ± 47.33 µg, respectively) or Type II Collagen gene expression. As such, the use of negative printing represents a promising solution for the integration of bulk reinforcement without losing the ability to produce new chondrogenic matrix.

NEST3D printed bone-mimicking scaffolds: assessment of the effect of geometrical design on stiffness and angiogenic potential.

Tissue-engineered implants for bone regeneration require consideration regarding their mineralization and vascularization capacity. Different geometries, such as biomimetic designs and lattices, can influence the mechanical properties and the vascularization capacity of bone-mimicking implants. Negative Embodied Sacrificial Template 3D (NEST3D) printing is a versatile technique across a wide range of materials that enables the production of bone-mimicking scaffolds. In this study, different scaffold motifs (logpile, Voronoi, and trabecular bone) were fabricated via NEST3D printing in polycaprolactone to determine the effect of geometrical design on stiffness (10.44 ± 6.71, 12.61 ± 5.71, and 25.93 ± 4.16 MPa, respectively) and vascularization. The same designs, in a polycaprolactone scaffold only, or when combined with gelatin methacryloyl, were then assessed for their ability to allow the infiltration of blood vessels in a chick chorioallantoic membrane (CAM) assay, a cost-effective and time-efficient in ovo assay to assess vascularization. Our findings showed that gelatin methacrylolyl alone did not allow new chorioallantoic membrane tissue or blood vessels to infiltrate within its structure. However, polycaprolactone on its own or when combined with gelatin methacrylolyl allowed tissue and vessel infiltration in all scaffold designs. The trabecular bone design showed the greatest mineralized matrix production over the three designs tested. This reinforces our hypothesis that both biomaterial choice and scaffold motifs are crucial components for a bone-mimicking scaffold.

Financial Toxicity Order Set: Implementing a Simple Intervention to Better Connect Patients With Resources.

PURPOSE: Financial toxicity of cancer treatment is well described in the literature, including characterizations of its risk factors, manifestations, and consequences. There is, however, limited research on interventions, particularly those at the hospital level, to address the issue. METHODS: From March 1, 2019, to February 28, 2022, a multidisciplinary team conducted a three-cycle Plan-Do-Study-Act (PDSA) process to develop, test, and implement an electronic medical record (EMR) order set to directly refer patients to a hospital-based financial assistance program. The cycles included an assessment of the efficacy of our current practice in connecting patients experiencing financial hardship with assistance, the development and piloting of the EMR referral order, and the broad implementation of the order set across our institution. RESULTS: In PDSA cycle 1, we found that approximately 25% of patients at our institution experienced some form of financial hardship, but most patients were not connected to available resources because of our referral mechanism. In PDSA cycle 2, the pilot referral order set was deemed feasible and received positive feedback. Over the 12-month study period (March 1, 2021-February 28, 2022) of PDSA cycle 3, 718 orders were placed for 670 unique patients across interdisciplinary providers from 55 treatment areas. These referrals resulted in at least $850,000 in US dollars (USD) in financial aid in 38 patients (mean = $22,368 USD). CONCLUSION: The findings from our three-cycle PDSA quality improvement project demonstrate the feasibility and efficacy of interdisciplinary efforts to develop a hospital-level financial toxicity intervention. A simple referral mechanism can empower providers to connect patients in need with available resources.

Within or Without You? A Perspective Comparing In Situ and Ex Situ Tissue Engineering Strategies for Articular Cartilage Repair.

Human articular cartilage has a poor ability to self-repair, meaning small injuries often lead to osteoarthritis, a painful and debilitating condition which is a major contributor to the global burden of disease. Existing clinical strategies generally do not regenerate hyaline type cartilage, motivating research toward tissue engineering solutions. Prospective cartilage tissue engineering therapies can be placed into two broad categories: i) Ex situ strategies, where cartilage tissue constructs are engineered in the lab prior to implantation and ii) in situ strategies, where cells and/or a bioscaffold are delivered to the defect site to stimulate chondral repair directly. While commonalities exist between these two approaches, the core point of distinction-whether chondrogenesis primarily occurs "within" or "without" (outside) the body-can dictate many aspects of the treatment. This difference influences decisions around cell selection, the biomaterials formulation and the surgical implantation procedure, the processes of tissue integration and maturation, as well as, the prospects for regulatory clearance and clinical translation. Here, ex situ and in situ cartilage engineering strategies are compared: Highlighting their respective challenges, opportunities, and prospects on their translational pathways toward long term human cartilage repair.

Characterization of Polycaprolactone Nanohydroxyapatite Composites with Tunable Degradability Suitable for Indirect Printing.

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.

Cross-Sector Approach Expands Screening and Addresses Health-Related Social Needs in Primary Care.

OBJECTIVES: During infancy, the American Academy of Pediatrics Bright Futures fourth edition health supervision guidelines recommend frequent well-child visits (WCVs) in which providers are expected to screen for and address maternal depression, intimate partner violence (IPV), and health-related social needs (HRSN). We spread an evidence-based approach that implements these recommendations (Developmental Understanding and Legal Collaboration for Everyone; DULCE) with 3 aims for 6-month-old infants and their families: 75% receive all WCVs on time, 95% are screened for 7 HRSNs, and 90% of families with concrete supports needs and 75% of families with maternal depression or IPV receive support. METHODS: Between January 2017 and July 2018, five DULCE teams (including a community health worker, early childhood system representative, legal partner, clinic administrator, pediatric and behavioral health clinicians) from 3 communities in 2 states participated in a learning collaborative. Teams adapted DULCE using Plan-Do-Study-Act cycles, reported data, and shared learning monthly. Run charts were used to study measures. The main outcome was the percent of infants that received all WCVs on time. RESULTS: The percentage of families who completed all WCVs on time increased from 46% to 65%. More than 95% of families were screened for HRSNs, 70% had ≥1 positive screen, and 86% and 71% of those received resource information for concrete supports and maternal depression and IPV, respectively. CONCLUSIONS: Quality improvement-supported DULCE expansion increased by 50% the proportion of infants receiving all WCVs on time and reliably identified and addressed families' HRSNs, via integration of existing resources.

FLASH: Fluorescently LAbelled Sensitive Hydrogel to monitor bioscaffolds degradation during neocartilage generation.

Regenerative therapies based on photocrosslinkable hydrogels and stem cells are of growing interest in the field of cartilage repair. Cell-mediated degradation is critical for the successful clinical translation of implanted hydrogels. However, characterising cell-mediated degradation, while simultaneously monitoring the deposition of a distinct new matrix, remains a major challenge. In this study we generated a Fluorescently LAbelled Sensitive Hydrogel (FLASH) to correlate the degradation of a hydrogel bioscaffold with neocartilage formation. Gelatine Methacryloyl (GelMA) was covalently bound to the FITC fluorophore to generate FLASH and bioscaffolds were produced by casting different concentrations of FLASH GelMA, with and without human adipose-derived stem cells (hADSCs) undergoing chondrogenesis. The loss of fluorescence from FLASH bioscaffolds was correlated with changes in mechanical properties, expression of chondrogenic markers and accumulation of a cartilaginous extracellular matrix. The ability of the system to be used as a sensor to monitor bioscaffold degradability during chondrogenesis was evaluated in vitro, in a human ex vivo model of cartilage repair and in a full chondral defect in vivo rabbit model. This study represents a step towards the generation of a high throughput monitoring system to evaluate de novo cartilage formation in tissue engineering therapies.

Protocols for Culturing and Imaging a Human Ex Vivo Osteochondral Model for Cartilage Biomanufacturing Applications.

Cartilage defects and diseases remain major clinical issues in orthopaedics. Biomanufacturing is now a tangible option for the delivery of bioscaffolds capable of regenerating the deficient cartilage tissue. However, several limitations of in vitro and experimental animal models pose serious challenges to the translation of preclinical findings into clinical practice. Ex vivo models are of great value for translating in vitro tissue engineered approaches into clinically relevant conditions. Our aim is to obtain a viable human osteochondral (OC) model to test hydrogel-based materials for cartilage repair. Here we describe a detailed step-by-step framework for the generation of human OC plugs, their culture in a perfusion device and the processing procedures for histological and advanced microscopy imaging. Our ex vivo OC model fulfils the following requirements: the model is metabolically stable for a relevant culture period of 4 weeks in a perfusion bioreactor, the processing procedures allowed for the analysis of 3 different tissues or materials (cartilage, bone and hydrogel) without compromising their integrity. We determined a protocol and the settings for a non-linear microscopy technique on label free sections. Furthermore, we established a clearing protocol to perform light sheet-based observations on the cartilage layer without the need for tedious and destructive histological procedures. Finally, we showed that our OC system is a clinically relevant in terms of cartilage regeneration potential. In conclusion, this OC model represents a valuable preclinical ex vivo tool for studying cartilage therapies, such as hydrogel-based bioscaffolds, and we envision it will reduce the number of animals needed for in vivo testing.

Relation of school environment and policy to adolescent physical activity.

BACKGROUND: Physical activity (PA) declines as children and adolescents age. The purpose of this study was to examine how specific school factors relate to youth PA, TV viewing, and body mass index (BMI). METHODS: A sample of 12- to 18-year-old adolescents in 3 cities (N = 165, 53% females, mean age 14.6 +/- 1.7 years, 44% nonwhite) completed surveys assessing days of physical education (PE) class per week, school equipment accessibility, after-school supervised PA, and after-school field access. Regression analyses were conducted to examine relationships between these school factors and PA at school facilities open to the public (never active vs active), overall PA level (days per week physically active for 60 minutes), BMI z score, and TV watching (hours per week). RESULTS: Adjusting for demographics, days of PE per week and access to school fields after school were correlated with overall PA (beta= 0.286, p = .002, semipartial correlation .236 and beta= 0.801, p = .016, semipartial correlation .186, respectively). The association between after-school field access and overall PA was mediated by use of publicly accessible school facilities for PA. After-school supervised PA and school PA equipment were not associated with overall PA. In adjusted regression analyses including all school factors, days of PE remained correlated to overall PA independent of other school factors (beta= 0.264, p = .007, semipartial correlation = .136). There were no associations between school factors and BMI or TV watching. CONCLUSIONS: Based on these study findings, PE is a promising intervention to address improving overall adolescent PA within the school setting.