Costs of care and financial hardship among patients with heart failure.

With the implementation of new therapies, more patients are living with heart failure (HF) as a chronic condition. Alongside these advances, out-of-pocket (OOP) medical costs have increased, and patients experience significant financial burden. Despite increasing interest in understanding and mitigating financial burdens, there is a relative paucity of data specific to HF. Here, we explore financial hardship in HF from the patient perspective, including estimated OOP costs for guideline-directed medical therapy for HF with reduced ejection fraction, hospitalizations, and total direct medical costs, as well as the consequences of high OOP costs. Studies estimate that high OOP costs are common in HF, and a large proportion are related to prescription drugs. Subsequently, the effects on patients can lead to worsening adherence, delayed care, and poor outcomes, leading to a financial toxicity spiral. Further, we summarize patients' cost preferences and outline future research that is needed to develop evidence-based solutions to reduce costs in HF.

Guideline Adherence and Practice Patterns in the Management of Medullary Thyroid Cancer.

INTRODUCTION: Little is known about nationwide practice patterns for the management medullary thyroid cancer (MTC) in relation to the 2015 American Thyroid Association guidelines and their impact on survival. METHODS: Using the Surveillance, Epidemiology, and End Results Program database (2000-2018), MTC treatment patterns were evaluated in terms of adherence to the 2015 American Thyroid Association guidelines across three time periods (2000-2009, 2010-2015, and 2016-2018). Outcomes of interest were guideline concordance, treatment utilization trends, disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 3332 patients with MTC were identified. Of which, 53.8%, 33.2%, and 11.4% of patients had localized, regional, and distant disease, respectively. In patients with locoregional disease, the rate of guideline-concordant surgery improved over time from 63.0% in 2000-2009 to 76.0% in 2016-2018 (P < 0.001). Guideline-concordant care was associated with increased OS (HR = 1.85, 95% CI: 1.42-2.43, P < 0.001) in patients with localized disease and increased DSS (HR = 1.65, 95% CI: 1.01-2.54, P < 0.001) and OS (HR = 1.89, 95% CI: 1.35-2.58, P < 0.001) in patients with regional disease. The median OS and DSS in patients with distant disease were 31 and 55 mo, respectively, and the rate of chemotherapy use rose from 21.6% to 39.2% (P = 0.003). CONCLUSIONS: The rate of guideline-concordant surgery for locoregional MTC increased after guideline publication in 2015, with an observed prolongment in OS and DSS. Chemotherapy use among patients with distant disease has increased over time, but their prognosis remains variable.

Navigating the high costs of cancer care: opportunities for patient engagement.

Over the past decade, the financial burden of cancer care on patients and their families has garnered increased attention. Many of the potential solutions have focused on system-level interventions such as adopting value-based payment models and negotiating drug prices; less consideration has been given to actions at the patient level to address cancer care costs. We argue that it is imperative to develop and support patient-level strategies that engage patients and consider their preferences, values and individual circumstances. Opportunities to meet these aims and improve the economic experience of patients in oncology are discussed, including: shared decision-making and communication, financial navigation and treatment planning, digital technology and alternative care pathways, and value-based insurance design.

Lay abstract The financial burden of cancer care on patients and their families is a growing problem and action is critically needed to alleviate the high costs of such care. So far, potential solutions have focused on system-level interventions, with less consideration given to solutions at the patient level. This review argues that it is imperative to develop and support patient-level strategies that engage patients. Next, the review presents evidence of the interplay between patient preferences and values and the costs of cancer care. Finally, opportunities to enhance engagement and improve the economic experience of patients in oncology are discussed, including: shared decision-making and communication, financial navigation and treatment planning, digital technology and alternative care pathways, and value-based insurance design.

Ovarian tissue transport to expand access to fertility preservation: from animals to clinical practice.

Primordial follicles dictate a female's reproductive life span and therefore are central to fertility preservation for both endangered species and individuals with fertility-threatening conditions. Ovarian tissue containing primordial follicles can be cryopreserved and later thawed and transplanted back into individuals to restore both endocrine function and fertility. Importantly, increasing numbers of human live births have been reported following ovarian tissue cryopreservation and transplantation. A current limitation of this technology is patient access to sites that are approved or equipped to process and cryopreserve ovarian tissue - especially in larger countries or low resource settings. Here, we review empirical evidence from both animal models and human studies that suggest that ovarian tissue can be transported at cold temperatures for several hours while still maintaining the integrity and reproductive potential of the primordial follicles within the tissue. In fact, several human live births have been reported in European countries using tissue that was transported at cold temperatures for up to 20 h before cryopreservation and transplantation. Ovarian tissue transport, if implemented widely in clinical practice, could therefore expand both patient and provider access to emerging fertility preservation options.

Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial.

BACKGROUND: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. METHODS/DESIGN: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. DISCUSSION: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02560922 , registered 9/22/2015.

Physical therapy vs. internet-based exercise training (PATH-IN) for patients with knee osteoarthritis: study protocol of a randomized controlled trial.

BACKGROUND: Physical activity improves pain and function among individuals with knee osteoarthritis (OA), but most people with this condition are inactive. Physical therapists play a key role in helping people with knee OA to increase appropriate physical activity. However, health care access issues, financial constraints, and other factors impede some patients from receiving physical therapy (PT) for knee OA. A need exists to develop and evaluate other methods to provide physical activity instruction and support to people with knee OA. This study is examining the effectiveness of an internet-based exercise training (IBET) program designed for knee OA, designed by physical therapists and other clinicians. METHODS/DESIGN: This is a randomized controlled trial of 350 participants with symptomatic knee OA, allocated to three groups: IBET, standard PT, and a wait list (WL) control group (in a 2:2:1 ratio, respectively). The study was funded by the Patient Centered Outcomes Research Institute, which conducted a peer review of the proposal. The IBET program provides patients with a tailored exercise program (based on functional level, symptoms, and current activity), video demonstrations of exercises, and guidance for appropriate exercise progression. The PT group receives up to 8 individual visits with a physical therapist, mirroring standard practice for knee OA and with an emphasis on a home exercise program. Outcomes are assessed at baseline, 4 months (primary time point) and 12 months (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include objective physical function, satisfaction with physical function, physical activity, depressive symptoms and global assessment of change. Linear mixed models will be used to compare both the IBET and standard PT groups to the WL control group, examine whether IBET is non-inferior to PT (a treatment that has an established evidence base for knee OA), and explore whether participant characteristics are associated with differential effects of IBET and/or standard PT. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill. DISCUSSION: The IBET program could be disseminated widely at relatively low cost and could be an important resource for helping patients with knee OA to adopt and maintain appropriate physical activity. This trial will provide an important evaluation of the effectiveness of this IBET program for knee OA. TRIAL REGISTRATION: NCT02312713.

Medullary thyroid cancer with RET V804M mutation: more indolent than expected?

BACKGROUND: Significant genotype-phenotype variability among multiple endocrine neoplasia type 2A patients with a RET V804M mutation has been reported. METHODS: Patients with a RET V804M mutation treated at a single center were identified (January 1996-December 2020). The baseline characteristics, operative details, pathology, biochemical, and long-term data were analyzed. RESULTS: There were 79 patients; none developed pheochromocytoma or hyperparathyroidism or died in the study period. The mean age was 41.5 years (range = 1.0-81.0 years); 46.8% were men. Of 68 surgical patients, 53 (77.9%) underwent total thyroidectomy and 15 (22.1%) underwent total thyroidectomy with central neck dissection with or without lateral neck dissection. Twenty-four patients had elevated preoperative calcitonin, of whom 12 underwent total thyroidectomy (median = 7.5; range = 5.0-237.0 pg/mL), 10 underwent total thyroidectomy + central neck dissection (median = 27.6; range = 5.1-147.0 pg/mL), and 2 underwent total thyroidectomy + central neck dissection + lateral neck dissection (median = 3182.0; range = 361.0-6003.0 pg/mL). Pathology was benign (27.9%), papillary thyroid cancer alone (1.5%), C-cell hyperplasia (23.5%), and medullary thyroid cancer (47.1%; median tumor size = 3.0 mm). Three patients had elevated calcitonin postoperatively (median follow-up time = 60.0 months). In adjusted modeling, a preoperative calcitonin >5 pg/mL was associated with having medullary thyroid cancer on final pathology (odds ratio = 13.3; 95% confidence interval, 3.2-56.3; P < .001). CONCLUSION: In this large United States cohort of surgical patients with a RET V804M mutation, most had indolent disease and were without classic multiple endocrine neoplasia type 2A features. Calcitonin >5 pg/mL may serve as a meaningful value to guide surveillance and timing of surgery.

Tumor marker response to SARS-CoV-2 infection among patients with cancer.

BACKGROUND: Inflammatory responses from benign conditions can cause non-cancer-related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS-CoV-2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID-19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID-19. However, available data excludes cancer patients, so little is known about the effect of COVID-19 on tumor markers among cancer patients. METHODS: We conducted a case series and identified patients with a positive SARS-CoV-2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19-9, CA 125, or CA 27-29 laboratory test. Cancer patients with documented COVID-19 infection and at least one pre- and two post-infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID-19 infection, and tumor marker values. RESULTS: Seven patients were identified with a temporary elevation of tumor marker values during the post-COVID-19 period. Elevation in tumor marker occurred within 56 days of COVID-19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post-infectious period among all patients. CONCLUSION: We report temporary elevations of cancer tumor markers in the period surrounding COVID-19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research.

Patient-Reported Outcomes Following Total Thyroidectomy for Graves' Disease.

Background: Graves' disease accounts for ∼80% of all cases of hyperthyroidism and is associated with significant morbidity and decreased quality of life. Understanding the association of total thyroidectomy with patient-reported quality-of-life and thyroid-specific symptoms is critical to shared decision-making and high-quality care. We estimate the change in patient-reported outcomes (PROs) before and after surgery for patients with Graves' disease to inform the expectations of patients and their physicians. Methods: PROs using the MD Anderson Symptom Inventory (MDASI) validated questionnaire were collected prospectively from adult patients with Graves' disease from January 1, 2015, to November 20, 2020, on a longitudinal basis. Survey responses were categorized as before surgery (≤120 days), short term after surgery (<30 days; ST), and long term after surgery (≥30 days; LT). Negative binomial regression was used to estimate the association of select covariates with PROs. Results: Eighty-five patients with Graves' disease were included. The majority were female (83.5%); 47.1% were non-Hispanic white and 35.3% were non-Hispanic black. The median thyrotropin (TSH) value before surgery was 0.05, which increased to 0.82 in ST and 1.57 in LT. In bivariate analysis, the Total Symptom Burden Score, a composite of all patient-reported burden, significantly reduced shortly after surgery (before surgery mean of 56.88 vs. ST 39.60, p < 0.001), demonstrating improvement in PROs. Furthermore, both the Thyroid Symptoms Score, including patient-reported thermoregulation, palpitations, and dysphagia, and the Quality-of-Life Symptom Score improved in ST and LT (thyroid symptoms, before surgery 13.88 vs. ST 8.62 and LT 7.29; quality of life, before surgery 16.16 vs. ST 9.14 and LT 10.04, all p < 0.05). After multivariate adjustment, the patient-reported burden in the Thyroid Symptom Score and the Quality-of-Life Symptom Score exhibited reduction in ST (thyroid symptoms, rate ratio [RR] 0.55, confidence interval [CI]: 0.42-0.72; quality of life, RR 0.57, CI: 0.40-0.81) and LT (thyroid symptoms, RR 0.59, CI: 0.44-0.79; quality of Life, RR 0.43, CI: 0.28-0.65). Conclusions: Quality of life and thyroid-specific symptoms of Graves' patients improved significantly from their baseline before surgery to both shortly after and longer after surgery. This work can be used to guide clinicians and patients with Graves' disease on the expected outcomes following total thyroidectomy.

The Emergency Department as an Opportunity for Naloxone Distribution.

INTRODUCTION: Substance use disorders, including opioid use disorders, are a major public health concern in the United States. Between 2005 and 2014, the rate of opioid-related emergency department (ED) visits nearly doubled, from 89.1 per 100,000 persons in 2005 to 177.7 per 100,000 persons in 2014. Thus, the ED presents a distinctive opportunity for harm-reduction strategies such as distribution of naloxone to patients who are at risk for an opioid overdose. METHODS: We conducted a systematic review of all existing literature related to naloxone distribution from the ED. We included only those articles published in peer-reviewed journals that described results relating to naloxone distribution from the ED. RESULTS: Of the 2,286 articles we identified from the search, five met the inclusion criteria and had direct relevance to naloxone distribution from the ED setting. Across the studies, we found variation in the methods of implementation and evaluation of take-home naloxone programs in the ED. In the three studies that attempted patient follow-up, success was low, limiting the evidence for the programs' effectiveness. Overall, in the included studies there is evidence that distributing take-home naloxone from the ED has the potential for harm reduction; however, the uptake of the practice remained low. Barriers to implementation included time allocated for training hospital staff and the burden on workflow. CONCLUSION: This systematic review of the best evidence available supports the ED as a potential setting for naloxone distribution for overdose reversal in the community. The variability of the implementation methods across the studies highlights the need for future research to determine the most effective practices.

Fear of Movement and Associated Factors Among Adults With Symptomatic Knee Osteoarthritis.

OBJECTIVE: To examine the frequency of and factors associated with fear of movement (FOM) among patients with symptomatic knee osteoarthritis (KOA), using the new Brief Fear of Movement (BFOM) measure. METHODS: Participants (n = 350) enrolled in a clinical trial completed the BFOM scale prior to randomization. The relationships of BFOM with the following characteristics were examined: age, sex, race, education, pain and activities of daily living (ADL) subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee symptom duration, depressive symptoms (8-item Patient Health Questionnaire [PHQ-8]), history of falls and knee injury, family history of knee problems, self-efficacy for exercise (SEE), and unilateral balance test. A proportional odds logistic regression model examined multivariable associations of participant characteristics with a 3-level BFOM variable (agreement with 0, 1-2, or ≥3 items). RESULTS: The majority of participants (77%) agreed with at least 1 item on the BFOM scale, and 36% endorsed 3+ items, suggesting a high degree of FOM. In the multivariable model, the following remained significant after backward selection: age (odds ratio [OR] 0.79 per 10-point increase, 95% confidence interval [95% CI] 0.66-0.95), KOOS ADL (OR 0.86 per 10-point increase, 95% CI 0.76-0.97), PHQ-8 (OR 1.15, 95% CI 1.08-1.22), and SEE (OR 0.87 per 10-point increase, 95% CI 0.78-0.96). CONCLUSION: FOM was common among patients with symptomatic KOA, and this could negatively impact physical activity. Psychological variables were significantly associated with FOM, suggesting behavioral and psychological interventions may decrease FOM and improve outcomes among individuals with symptomatic KOA.

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods.

PURPOSE: Fertility preservation in a pediatric and teen female population is challenging because standard technologies of egg and embryo freezing may not be possible due to premenarcheal status. Ovarian tissue cryopreservation (OTC) with the intent of future ovarian tissue transplantation or in vitro follicle growth may be the only option to preserve fertility. The purpose of this study was to add to the general understanding of primordial follicle dynamics in young patients. METHODS: First, the unique infrastructure of the Oncofertility Consortium National Physicians Cooperative (OC-NPC) is described, which simultaneously drives clinical fertility preservation and basic research to explore and expand the reproductive options for those in need. Then, the OC-NPC research resource is used to perform a histological evaluation of ovarian tissue from 24 participants younger than 18 years of age. RESULTS: Primordial follicles, which comprise the ovarian reserve, were observed in all participant tissues, irrespective of variables, including age, diagnosis, previous treatment history, tissue size, and tissue processing methods. Primordial follicles were present in ovarian tissue, even in participants who had a previous history of exposure to chemotherapy and/or radiation treatment regimens, which placed them at risk for iatrogenic infertility or premature ovarian failure. CONCLUSION: Primordial follicles were observed in ovarian tissue from all participants examined, despite population and tissue heterogeneity. These results increase the understanding of human follicle dynamics and support OTC as a promising fertility preservation modality in the young female population. Future studies to evaluate follicle quality within these tissues are warranted.