A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

Examining the Association between Abstinence from Smoking and Healthcare Costs Among Patients with Cancer.

Continuous tobacco use in cancer patients is linked to substantial healthcare costs due to increased risks and complications, whereas quitting smoking leads to improved treatment outcomes and cost reductions. Addressing the need for empirical evidence on the economic impact of smoking cessation, this study examined the association between smoking cessation and healthcare cost utilization among a sample of 930 cancer patients treated at The University of Texas MD Anderson Cancer Center's Tobacco Research and Treatment Program (TRTP). Applying conditional quantile regression and propensity scores to address confounding, our findings revealed that abstinence achieved through the TRTP significantly reduced the median cost during a 3-month period post-quitting by $1,095 (ß=-$1,095, p=0.007, 95%CI=[-$1,886, -$304]). Sensitivity analysis corroborated these conclusions, showing a pronounced cost reduction when outlier data were excluded. The long-term accrued cost savings from smoking cessation could potentially offset the cost of participation in the TRTP program, underscoring its cost-effectiveness. An important implication of this study is that by reducing smoking rates, healthcare systems can more efficiently allocate resources, enhance patient health outcomes, and lessen the overall cancer burden.

Impact of state telehealth policies on telehealth use among patients with newly diagnosed cancer.

BACKGROUND: Telehealth restrictions were relaxed under the COVID-19 public health emergency. We examined telehealth use before and during the pandemic among patients with newly diagnosed cancers and the association between state policies and telehealth use. METHODS: The study cohort was constructed from Optum's deidentified Clinformatics Data Mart and included patients with lymphoma, female breast cancer, colorectal cancer, prostate cancer, and lung cancer diagnosed between March 1, 2019, and March 31, 2021. We performed an interrupted time series analysis to examine the trend of cancer-related telehealth use within 1 month of diagnosis relative to the timing of the COVID-19 public health emergency and multivariable logistic regressions to examine factors-specifically, state parity laws and regulations on cross-state practice-associated with telehealth. RESULTS: Of 110 461 patients, the rate of telehealth use peaked at 33.4% in April 2020, then decreased to 12% to 15% between September 2020 and March 2021. Among the 53 982 patients diagnosed since March 2020, telehealth use was statistically significantly lower for privately insured patients residing in states with coverage-only parity or no or unspecified parity than those in states with coverage and payment parity (adjusted rate = 20.2%, 19.1%, and 23.3%, respectively). The adjusted rate was lower for patients in states with cross-state telehealth policy limitations than for those in states without restrictions (14.9% vs 17.8%). CONCLUSIONS: Telehealth use by patients diagnosed with cancer during the pandemic was higher among those living in states with more generous parity and less restrictive rules for cross-state practice. Policy makers contemplating whether to permanently relax certain telehealth policies must consider the impact on vulnerable patient populations who can benefit from telehealth.

Current Trends in the Utilization of Preoperative Breast Magnetic Resonance Imaging Among Women With Newly Diagnosed Breast Cancer.

PURPOSE: The clinical benefit of preoperative breast magnetic resonance imaging (MRI) for early-stage breast cancer (BC) remains controversial. We examined trends and the associated factors of preoperative breast MRI use. METHODS: This study cohort, constructed from Optum Clinformatics database, included women with early-stage BC who had a cancer surgery between March 1, 2008, and December 31, 2020. Preoperative breast MRI was performed between the date of BC diagnosis and index surgery. Multivariable logistic regressions, one for elderly (65 years and older) and the other for non-elderly patients (younger than 65 years), were performed to examine factors associated with the use of preoperative MRI. RESULTS: Among 92,077 women with early-stage BC, the crude rate of preoperative breast MRI increased from 48% in 2008 to 60% in 2020 for nonelderly and from 27% to 34% for elderly women. For both age groups, non-Hispanic Blacks were less likely (odds ratio [OR]; 95% CI, younger than 65 years: 0.75, 0.70 to 0.81; 65 years and older: 0.77, 0.72 to 0.83) to receive preoperative MRI than non-Hispanic White patients. Across Census divisions, the highest adjusted rate was observed in Mountain division (OR compared with New England; 95% CI, younger than 65 years: 1.45, 1.27 to 1.65; 65 years and older: 2.42, 2.16 to 2.72). Other factors included younger age, fewer comorbidities, family history of BC, axillary node involvement, and neoadjuvant chemotherapy for both age groups. CONCLUSION: The use of preoperative breast MRI has steadily increased. Aside from clinical factors, age, race/ethnicity, and geographic location were associated with preoperative MRI use. This information is important for future implementation or deimplementation strategies of preoperative MRI.

Neuroprotective Effects of a Multi-Herbal Extract on Axonal and Synaptic Disruption in Vitro and Cognitive Impairment in Vivo.

Background: Alzheimer's disease (AD) is a multifactorial disorder characterized by cognitive decline. Current available therapeutics for AD have limited clinical benefit. Therefore, preventive therapies for interrupting the development of AD are critically needed. Molecules targeting multifunction to interact with various pathlogical components have been considered to improve the therapeutic efficiency of AD. In particular, herbal medicines with multiplicity of actions produce cognitive benefits on AD. Bugu-M is a multi-herbal extract composed of Ganoderma lucidum (Antler form), Nelumbo nucifera Gaertn., Ziziphus jujuba Mill., and Dimocarpus longan, with the ability of its various components to confer resilience to cognitive deficits. Objective: To evaluate the potential of Bugu-M on amyloid-ß (Aß) toxicity and its in vitro mechanisms and on in vivo cognitive function. Methods: We illustrated the effect of Bugu-M on Aß25-35-evoked toxicity as well as its possible mechanisms to diminish the pathogenesis of AD in rat cortical neurons. For cognitive function studies, 2-month-old female 3×Tg-AD mice were administered 400 mg/kg Bugu-M for 30 days. Behavioral tests were performed to assess the efficacy of Bugu-M on cognitive impairment. Results: In primary cortical neuronal cultures, Bugu-M mitigated Aß-evoked toxicity by reducing cytoskeletal aberrations and axonal disruption, restoring presynaptic and postsynaptic protein expression, suppressing mitochondrial damage and apoptotic signaling, and reserving neurogenic and neurotrophic factors. Importantly, 30-day administration of Bugu-M effectively prevented development of cognitive impairment in 3-month-old female 3×Tg-AD mice. Conclusion: Bugu-M might be beneficial in delaying the progression of AD, and thus warrants consideration for its preventive potential for AD.

Assessment of Uptake Appropriateness of Computed Tomography for Lung Cancer Screening According to Patients Meeting Eligibility Criteria of the US Preventive Services Task Force.

Importance: Currently, computed tomography (CT) is used for lung cancer screening (LCS) among populations with various levels of compliance to the eligibility criteria from the US Preventive Services Task Force (USPSTF) recommendations and may represent suboptimal allocation of health care resources. Objective: To evaluate the appropriateness of CT LCS according to the USPSTF eligibility criteria. Design, Setting, and Participants: This cross-sectional study used the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Participants included individuals who responded to the LCS module administered in 20 states and had valid answers to questions regarding screening and smoking history. Data were analyzed between October 2021 and August 2022. Exposures: Screening eligibility groups were categorized according to the USPSTF 2013 recommendations, and subgroups of individuals who underwent LCS were analyzed. Main Outcomes and Measures: Main outcomes included LCS among the screening-eligible population and the proportions of the screened populations according to compliance categories established from the USPSTF 2013 and 2021 recommendations. In addition, the association between respondents' characteristics and LCS was evaluated for the subgroup who were screened despite not meeting any of the 3 USPSTF screening criteria: age, pack-year, and years since quitting smoking. Results: A total of 96 097 respondents were identified for the full study cohort, and 2 subgroups were constructed: (1) 3374 respondents who reported having a CT or computerized axial tomography to check for lung cancer and (2) 33 809 respondents who did not meet any screening eligibility criteria. The proportion of participants who were under 50 years old was 53.1%; between 50 and 54, 9.1%; between 55 and 79, 33.8%; and over 80, 4.0%. A total of 51 536 (50.9%) of the participants were female. According to the USPSTF 2013 recommendation, 807 (12.8%) of the screening-eligible population underwent LCS. Among those who were screened, only 807 (20.9%) met all 3 screening eligibility criteria, whereas 538 (20.1%) failed to meet any criteria. Among respondents in subgroup 2, being of older age and having a history of stroke, chronic obstructive pulmonary disease, kidney disease, or diabetes were associated with higher likelihood of LCS. Conclusions and Relevance: In this cross-sectional study of the BRFSS 2019 survey, the low uptake rate among screening-eligible patients undermined the goal of LCS of early detection. Suboptimal screening patterns could increase health system costs and add financial stress, psychological burden, and physical harms to low-risk patients, while failing to provide high-quality preventive services to individuals at high risk of lung cancer.

Growing Financial Burden From High-Cost Targeted Oral Anticancer Medicines Among Medicare Beneficiaries With Cancer.

PURPOSE: The rapidly rising costs of targeted oral anticancer medicines (TOAMs) raise concerns over their affordability. Our goal was to examine recent trends in the uptake of TOAMs among cancer patients with Medicare Part D, the share of TOAM users who reached catastrophic coverage, and the annual spending on TOAMs in the catastrophic phase. METHODS: Using the 5% SEER-Medicare, we included patients age 65 years and older who had one primary cancer diagnosis between 2011 and 2016. We included person-years where patients were enrolled in a Part D plan for the entire year, did not receive the low-income subsidy at any time of the year, and received anticancer systemic therapies. We estimated the trends in the share of patients who used TOAMs, the percentage of TOAM users reaching catastrophic coverage, and the total and patient out-of-pocket spending on TOAMs in the catastrophic phase in a year. RESULTS: From 2011 to 2016, the uptake of TOAMs among our study population increased from 3.6% to 8.9%. The percentage of non-low-income subsidy TOAM users who reached catastrophic coverage increased from 54.6% to 60.3%. Among those who reached the catastrophic phase, mean total gross spending on TOAMs in the catastrophic phase increased from $16,074 (USD) to $64,233 (USD) and mean patient out-of-pocket spending from $596 (USD) to $2,549 (USD). The mean 30-day total spending increased from $4,011 (USD) to $8,857 (USD), and the mean 30-day out-of-pocket spending from $154 (USD) to $328 (USD). CONCLUSION: The high and growing burden from TOAMs highlighted the need for reining in drug prices and capping out-of-pocket spending.

Multilayer Reversible Information Hiding with Prediction-Error Expansion and Dynamic Threshold Analysis.

The rapid development of internet and social media has driven the great requirement for information sharing and intelligent property protection. Therefore, reversible information embedding theory has marked some approaches for information security. Assuming reversibility, the original and embedded data must be completely restored. In this paper, a high-capacity and multilayer reversible information hiding technique for digital images was presented. First, the integer Haar wavelet transform scheme converted the cover image from the spatial into the frequency domain that was used. Furthermore, we applied dynamic threshold analysis, the parameters of the predicted model, the location map, and the multilayer embedding method to improve the quality of the stego image and restore the cover image. In comparison with current algorithms, the proposed algorithm often had better embedding capacity versus image quality performance.

Global Challenges in Access to and Implementation of Precision Oncology: The Health Care Manager and Health Economist Perspective.

Precision medicine changes the landscape of oncology practices by offering the opportunity to optimize care through a more targeted, personalized approach of managing cancer treatments. However, precision oncology is costly and does not benefit all patients with cancer, making it critically important to consider the tradeoff between costs and health benefits. Here, we discuss the global challenges in implementing precision oncology from the perspective of health care management and health economics and emphasize the different challenges for high-income compared with low- and middle-income countries. For health care managers making resource allocation decisions, the decision to adopt, implement, and finance precision oncology must consider opportunity costs, and the allocation must be proportional to the system's capacity. The standard approach of health technology assessment is inadequate because it fails to consider the capacity to pay. From an economic perspective, global implementation of precision oncology must confront the issues of accessibility, affordability, and system readiness. Low- and middle-income countries often have no or delayed access to novel targeted-therapy agents, find these drugs cost-prohibitive, and struggle to build the infrastructure with sufficient workforce and adequate testing and computing facilities to capitalize the benefit of precision oncology. Although high-income countries are better equipped to implement precision oncology, the challenges there lie in implementing strategies to maximize the value of precision oncology through promoting appropriate use while limiting inappropriate applications. The recent rollout of COVID-19 vaccines internationally highlights the importance of information uncertainty and offers valuable insights on global access to and implementation of precision oncology.

Impact of race-specific screening guideline on the uptake of colorectal cancer screening among young African Americans.

BACKGROUND: African Americans (AAs) have had lower colorectal cancer (CRC) screening rates, higher incidence rate, and earlier mean age at onset. The 2017 U.S. Multi-Society Task Force (MSTF) recommended initiating CRC screening at age 45 for AAs and age 50 for non-AAs. OBJECTIVE: To investigate the impact of the 2017 MSTF's race-specific guidelines on CRC screening rate among young AAs. DESIGN, SETTING, AND PARTICIPANTS: We used the 2015 and 2018 National Health Interview Survey to provide nationally representative estimates. The study sample included adults aged between 45 and 75 without a history of CRC, excluding screening recipients for diagnosis or surveillance purposes. MAIN MEASURES: The outcome is a binary variable of CRC screening. Primary independent variables were age and race category (non-AAs aged 45-49, AAs 45-49, non-AAs 50-75, AAs 50-75), a binary variable indicating before or after the 2017 MSTF guideline (2015 vs. 2018), and their interaction terms. We employed a multivariable logistic model, adjusting for individual characteristics, and accounting for complex survey design. KEY RESULTS: Among the total sample (n = 21,735), CRC screening rate increased from 54.6% in 2015 to 58.5% in 2018 (p < 0.01). By age and race, the screening rate exhibited an increase for all age and race groups except for young non-AAs. Compared to young non-AAs, the adjusted predicted probability (APP) of screening for young AAs was significantly higher by 0.10 (average marginal effect, 0.10; 95% confidence interval, 0.01-0.19) in 2018, while the difference was insignificant in 2015. Racial differences in screening among older adults were not significant in both years. The CRC screening rate was substantially lower among young AAs compared to older AAs (17.2% vs. 65.5% in 2018). CONCLUSION: The race-specific recommendation is an effective policy tool to increase screening uptake and would contribute to reducing cancer disparities among racial/ethnic minorities.

Psychometric Testing of the Newly Developed Competence Scale for Clinical Nurses.

BACKGROUND: Nursing competence is an essential element in ensuring high-quality nursing care and positive patient outcomes. Valid and reliable assessment tools for assessing nurse competence are needed to help nurse supervisors measure whether nurses are performing their job well and to provide a baseline for improving the competences of nurses. PURPOSE: This study was designed to develop and psychometrically validate the Competence Scale for Clinical Nurses (CSCN). METHODS: The CSCN was developed in three steps: (a) generalize assessment items from nursing competence-related scales and a review of the relevant literature, (b) determine the content validity of the developed scale, and (c) psychometrically test the developed scale. Five hundred nurses were recruited from a medical center in southern Taiwan. Exploratory and confirmatory factor analyses were executed to analyze construct validity and internal consistency reliability. RESULTS: The scale-content validity index was .87, as determined by five experts. Two thirds (63.29%) of the variance was explained by three factors: basic care skills (nine items), being dedicated to work (five items), and patient-centered and ethical considerations (four items). A second-order confirmatory factor analysis indicated that the data fit the model well. The Cronbach's alpha coefficients for each of the three factors and the total scale were .84-.91. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The 18-item CSCN is a feasible and time-efficient tool for assessing competence in clinical nurses. Nursing supervisors may use this tool to explore nurses' competency and routinely track the effect of continuing education on competence. Continuous evaluation of nurses' clinical-based competence using the CSCN is recommended.

Ethylene Response Factor109 Attunes Immunity, Photosynthesis, and Iron Homeostasis in Arabidopsis Leaves.

Iron (Fe) is an essential micronutrient element for all organisms including plants. Chlorosis of young leaves is a common symptom of Fe deficiency, reducing the efficiency of photosynthesis, and, ultimately, crop yield. Previous research revealed strong responsiveness of the putative key transcription factor ERF109 to the Fe regime. To elucidate the possible role of ERF109 in leaf Fe homeostasis and photosynthesis, we subjected Arabidopsis thaliana erf109 knockout lines and Col-0 wild-type plants to transcriptome profiling via RNA-seq. The transcriptome profile of Fe-sufficient erf109 leaves showed a 71% overlap with Fe-deficient Col-0 plants. On the other hand, genes that were differentially expressed between Fe-deficient and Fe-sufficient Col-0 plants remained unchanged in erf109 plants under conditions of Fe deficiency. Mutations in ERF109 increased the expression of the clade Ib bHLH proteins bHLH38, bHLH39, bHLH101, the nicotianamine synthase NAS4, and the Fe storage gene FER1. Moreover, mutations in ERF109 led to significant down-regulation of defense genes, including CML37, WRKY40, ERF13, and EXO70B2. Leaves of erf109 exhibited increased Fe levels under both Fe-sufficient and Fe-deficient conditions. Reduced Fv/Fm and Soil Plant Analysis Development (SPAD) values in erf109 lines under Fe deficiency indicate curtailed ability of photosynthesis relative to the wild-type. Our findings suggest that ERF109 is a negative regulator of the leaf response to Fe deficiency. It further appears that the function of ERF109 in the Fe response is critical for regulating pathogen defense and photosynthetic efficiency. Taken together, our study reveals a novel function of ERF109 and provides a systematic perspective on the intertwining of the immunity regulatory network and cellular Fe homeostasis.

Pinocembrin Reduces Keratinocyte Activation and Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis in BALB/c Mice through the Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Pathway.

Psoriasis is an autoimmune disease characterized by chronic skin inflammation and excessive keratinocyte proliferation. The itchy, scaly, and erythematous lesions present on psoriatic skin negatively affect patients' quality of life. Pinocembrin is a flavonoid present in propolis, fruits, and vegetables. It exerts neuroprotective effects and was used for treating ischemic stroke in a human clinical trial. However, the effects of pinocembrin on psoriasis have never been examined. In this study, we evaluated the effects of pinocembrin on human HaCaT keratinocytes and BALB/c mice with imiquimod- (IMQ-) induced psoriatic dermatitis. In interferon-γ- (IFN-γ-) activated HaCaT cells, pinocembrin reduced the expression of inflammatory cytokines, namely, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and keratinocyte proliferation markers, namely, keratin (K)16, K17, and Ki-67. The mechanism underlying these inhibitory effects involved the regulation of the heme oxygenase- (HO-) 1/signal transducer and activator of transcription (STAT) 3 pathway. In the IMQ-induced psoriatic dermatitis mouse model, the topical application of pinocembrin significantly ameliorated the Skin Psoriasis Area and Severity Index score, epidermal thickness, inflammation, hyperplasia, hyperkeratosis, and cluster of differentiation (CD) 4+ T-cell infiltration. Expression of the inflammatory cytokines and keratinocyte proliferation markers in dorsal skin was significantly decreased in the pinocembrin-treated group. Meanwhile, in lesional skin, the expression of HO-1 was upregulated, but that of phospho-STAT3 (pSTAT3) was downregulated. Collectively, our results indicated the therapeutic potential of pinocembrin. Additional studies are warranted to evaluate its clinical benefits in patients with psoriasis.

Complications and Failure to Rescue After Inpatient Pediatric Surgery.

OBJECTIVE: To describe the frequency and patterns of postoperative complications and FTR after inpatient pediatric surgical procedures and to evaluate the association between number of complications and FTR. SUMMARY AND BACKGROUND: FTR, or a postoperative death after a complication, is currently a nationally endorsed quality measure for adults. Although it is a contributing factor to variation in mortality, relatively little is known about FTR after pediatric surgery. METHODS: Cohort study of 200,554 patients within the National Surgical Quality Improvement Program-Pediatric database (2012-2016) who underwent a high (≥ 1%) or low (< 1%) mortality risk inpatient surgical procedures. Patients were stratified based on number of postoperative complications (0, 1, 2, or ≥3) and further categorized as having undergone either a low- or high-risk procedure. The association between the number of postoperative complications and FTR was evaluated with multivariable logistic regression. RESULTS: Among patients who underwent a low- (89.4%) or high-risk (10.6%) procedures, 14.0% and 12.5% had at least 1 postoperative complication, respectively. FTR rates after low- and high-risk procedures demonstrated step-wise increases as the number of complications accrued (eg, low-risk- 9.2% in patients with ≥3 complications; high-risk-36.9% in patients with ≥ 3 complications). Relative to patients who had no complications, there was a dose-response relationship between mortality and the number of complications after low-risk [1 complication - odds ratio (OR) 3.34 (95% CI 2.62-4.27); 2 - OR 10.15 (95% CI 7.40-13.92); ≥3-27.48 (95% CI 19.06-39.62)] and high-risk operations [1 - OR 3.29 (2.61-4.16); 2-7.24 (5.14-10.19); ≥3-20.73 (12.62-34.04)]. CONCLUSIONS: There is a dose-response relationship between the number of postoperative complications after inpatient surgery and FTR, ever after common, "minor" surgical procedures. These findings suggest FTR may be a potential quality measure for pediatric surgical care.

Cost-Sharing and Out-of-Pocket Cost for Women Who Received MRI for Breast Cancer Screening.

BACKGROUND: The financial protection of the prevention provision of the Affordable Care Act (ACA) doesn't apply to breast MRI but only to mammography for breast cancer screening. The purpose of the study is to examine the financial burden among women who received breast magnetic resonance imaging (MRI) for screening. METHODS: This observational study used the Marketscan database. Women who underwent breast MRI between 2009 and 2017 and had screening mammography within 6 months of the MRI were included. We compared the time trend of the proportion of zero cost-share for women undergoing screening mammography and that for MRI. We quantified out-of-pocket (OOP) costs as the sum of copayment, coinsurance, and deductible and defined zero cost-share as having no OOP cost. We conducted multivariable logistic regression and 2-part model to examine factors associated with zero cost-share and OOP costs of MRI, respectively. RESULTS: During the study period, 16 341 women had a screening breast MRI. The proportion of screening MRI claims with zero cost-share decreased from 43.1% (2009) to 26.2% (2017). The adjusted mean OOP cost for women in high-deductible plans was more than twice the cost for their counterparts ($549 vs $251; 2-sided P < .001). Women who resided in the South in the post-Affordable Care Act era were less likely to have zero cost-share and paid higher OOP costs for screening MRI. CONCLUSIONS: Many women are subject to high financial burden when receiving MRI for breast cancer screening. Those enrolled in high-deductible plans and who reside in the South are especially vulnerable financially.

A Systematic Review of Economic and Quality-of-Life Research in Carcinoid Syndrome.

BACKGROUND: To date, the economic burden and patient-reported outcomes associated with carcinoid syndrome (CS) in patients with neuroendocrine tumor (NET) remain largely unknown. OBJECTIVES: The objective of this study was to perform a systematic review of economic and quality-of-life (QOL) studies related to the treatment of CS. METHODS: Articles included in the review were extracted from PubMed, Embase, and the Cochrane Library. Studies had to be in English and published between 1 January 2000 and 2 July 2020. Other study eligibility criteria included patients with NET with CS receiving treatment for CS, study outcomes of cost or QOL, and clinical trials or population-based studies using claims or other secondary databases. The interventions included somatostatin analogs, telotristat ethyl, or other treatment for CS. To evaluate the quality and bias of the included studies, the 24-item CHEERS and 10-item Gill and Feinstein checklists were used. We report a narrative synthesis of the findings from the selected studies. RESULTS: A total of 12 economic and 12 QOL studies met the inclusion criteria and were included for review. Patients with uncontrolled CS symptoms had 23-92% higher costs than those with controlled CS; mostly, ambulatory/outpatient services were the primary drivers of the costs. The use of telotristat ethyl may be cost effective if the societal willingness to pay is as high as $US150,000 per quality-adjusted life-year in the USA. Of the 12 QOL papers, only three case-control studies assessed QOL at baseline and more than two follow-up time points. Seven studies evaluated QOL at two or more time points but lacked a control group, obscuring direct intervention effects on patients' well-being. CONCLUSIONS: We observed wide variations in the reviewed studies evaluating the economic burden and patient-reported outcomes, in terms of cost and QOL, of patients with CS. Although QOL is consistently impaired and costs are consistently increased by CS, the numbers of both cost and QOL studies among this patient population remain sparse, and many of the existing studies indicated an important need for quality improvement.

Malnutrition Affects the Outcomes of Patients with Low-Output Heart Failure and Congestion.

BACKGROUND: This study aimed to investigate the relationship between malnutrition and outcomes in patients with decompensated severe systolic heart failure (HF) focusing on clinical presentations and medication use. METHODS: This study prospectively enrolled 108 patients admitted for severe systolic HF with a left ventricular (LV) ejection fraction < 35%, low cardiac output, and high LV filling pressure. Five patients died during the index hospitalization, and the remaining 103 patients were followed up for 2 years. The primary endpoints were HF rehospitalization and all-cause mortality. Nutritional risk index (NRI) was calculated as (1.519 × serum albumin, g/L) + (41.7 × body weight/ideal body weight). RESULTS: Forty-four patients reached the study endpoints. An NRI ≤ 93 predicted events. The NRI ≤ 93 group had higher pulmonary artery systolic pressure, more edema over dependent parts, longer hospital stay, and more primary endpoints compared to the NRI > 93 group. The NRI ≤ 93 group received fewer evidence-based medications and more loop diuretics compared to the NRI > 93 group. NRI was an independent predictor of cardiovascular events [hazard ratio 0.902; 95% confidence interval (CI) 0.814-0.982 per 1 point increase; p = 0.012]. Low NRI was associated with a significantly higher use of loop diuretics [odds ratio (OR) 2.75; 95% CI 1.046-5.647; p = 0.004] and significantly lower use of beta blockers (OR 0.541; 95% CI 0.319-0.988; p = 0.002). CONCLUSIONS: Malnutrition assessed using the NRI was associated with cardiovascular events in the patients with severe systolic HF with low cardiac output and high LV filling pressure. Low NRI was associated with more diuretic and less beta blocker use.

Choice of local therapy for young women with early-stage breast cancer who have young-aged children.

BACKGROUND: Decision making regarding the initial treatment of women with breast cancer is complicated. In the current study, the authors examined the relationship between treatment choices and their children's ages among young women with early-stage breast cancer. METHODS: Using the MarketScan Commercial Claims and Encounters database, the authors identified women aged 20 to 50 years who underwent lumpectomy or mastectomy for early-stage breast cancer between 2008 and 2014. Predictors of compliance with radiotherapy after undergoing lumpectomy and of undergoing mastectomy were determined using multinomial logistic regression. The authors conducted sensitivity analyses to explore the impact of the number of young-aged children and a reduction in the sample size in 2014 due to the attrition of health plans contributing to MarketScan. RESULTS: A total of 21,052 women were included in the current analysis. Among women with at least 1 child aged <7 years, the adjusted rate of lumpectomy was 59.9%; approximately 22% of these women did not receive radiotherapy. Compared with women undergoing lumpectomy plus radiotherapy, women with at least 1 child aged <7 years or aged 7 to 12 years were 25% and 16%, respectively, more likely to undergo lumpectomy alone compared with women with no children aged <18 years (P = .002 and P = .012, respectively) and 64% and 37%, respectively, more likely to undergo mastectomy (P < .001). CONCLUSIONS: Among privately insured women with breast cancer, having young children was found to be strongly associated with the omission of postlumpectomy radiotherapy or undergoing mastectomy. Having >1 young-aged child further amplified these associations. The findings of the current study suggested that caring for young children may present unique challenges to young women with breast cancer.

Sociodemographic Factors in Pediatric Epilepsy Surgery.

BACKGROUND: Despite documented efficacy of surgical treatment in carefully selected patients, surgery is delayed and/or underutilized in both adult and children with focal onset epilepsy. The reasons for surgical delay are often assumed or theorized, and studies have predominantly targeted the adult population. To focus on a more targeted pediatric population and to determine identifiable reasons for intervention, this study aimed to investigate time to epilepsy surgery among pediatric patients with medically intractable epilepsy associated with focal cortical dysplasia and to identify sociodemographic and clinical associations in time to epilepsy surgery. METHODS: We reviewed 96 consecutive pediatric patients who underwent surgery for medically intractable epilepsy with a diagnosis of focal cortical dysplasia. Descriptive statistics, univariate and multivariate analyses were conducted to study the association of sociodemographic variables of patients with focal cortical dysplasia and time to epilepsy surgery and postoperative seizure control. RESULTS: We identified that non-white patients on average had a longer duration of epilepsy before surgery and traveled shorter distances for care. Non-white patients were more likely to have government-funded insurance. Patients who traveled the shortest distance to the surgical center underwent epilepsy surgery at an older age. CONCLUSIONS: Sociodemographic factors of travel distance, insurance, and race influenced time to epilepsy surgery for children with focal cortical dysplasia. Further research is warranted to target barriers in access to subspecialty care and develop ways to identify earlier the patients who may benefit from evaluation and deployment of surgical intervention.

Haematococcus pluvialis-Derived Astaxanthin Is a Potential Neuroprotective Agent against Optic Nerve Ischemia.

Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death via anti-oxidative and anti-apoptotic responses. Adult male Wistar rats were fed astaxanthin (100 mg/kg/day) by daily gavage for seven consecutive days, either before or after inducing oxidative stress in the retina by photodynamic treatment. The visual function, RGC apoptosis, macrophage infiltration in the optic nerve, expression of p-Akt, p-mTOR, SGK1, pS6K, Nrf2, p62, TNFα, Il1ß in retinas were investigated. The visual function and the RGC densities were significantly higher in both pre- and post-treatment groups. The numbers of apoptotic RGCs and extrinsic macrophage infiltration in the optic nerve were significantly decreased in both astaxanthin-treated groups. Furthermore, pre- and post-treatment of astaxanthin showed a higher expression of p-Akt, p-mTOR, Nrf2 and superoxide dismutase activity, and a lower expression of cleaved caspase-3, suggesting anti-apoptotic and anti-oxidative roles. Our findings indicate that astaxanthin can preserve visual function and reduce RGC apoptosis after ischemic insults. Including astaxanthin in daily diet as a supplement may be beneficiary for ischemic optic neuropathy.