Identifying the mediating role of inflammation on the relationship between socioeconomic status and Alzheimer's disease: a Mendelian randomization analysis and mediation analysis.

BACKGROUND AND OBJECTIVES: Observational studies have demonstrated a significant association between socio-economic status (SES) and Alzheimer's disease (AD). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian Randomization (MR) approach to investigate the causal relationship between SES and genetic susceptibility to AD, as well as to explore the potential mediation effects of inflammation. METHODS: Large-scale cohorts based on publicly available genome-wide association study (GWAS) datasets from European populations were employed for conducting the MR study. The primary criterion utilized was the inverse-variance weighting (IVW) model. Heterogeneity and horizontal pleiotropy were assessed. In addition, multivariate MR (MVMR) was utilized to correct the confounders. Moreover, a two-step MR approach was used to evaluate the potential mediating effects of factors on the causal effects between SES and AD. RESULTS: As indicated by the results of the IVW model, educational years (OR = 0.708, 95% CI 0.610-0.821, P < 0.001) and household income (OR = 0.746, 95% CI 0.566-0.982, P = 0.037) was associated with a decreased genetic susceptibility risk for AD. The univariable results showed that the causal effect of educational years on the lower risk of AD remained significant (OR = 0.643, 95% CI 0.467-0.886, P = 0.006). In addition, our findings indicated that C-reactive protein (CRP) played a role in the causal effect of educational years on AD. The proportions of mediation were - 50.08% (95% CI - 92.78; - 7.38%). DISCUSSION: These findings provided evidence supporting the causal effect of educational attainment lower AD risk, with inflammation playing a mediating role. These findings may inform prevention strategies and interventions directed toward AD. Future studies should explore other plausible biological mechanisms.

Emerging Roles of RNA Methylation in Development.

More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples.This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m6A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m5C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m1A, with a lower abundance than m6A, is widely distributed in various RNA types, mainly locates in the 5' untranslated region (5'UTR) of mRNA and regulates translation. RNA m7G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention.Thanks to the development of sequencing technology, m6A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m5C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m5C dependent manner. m1A also has been revealed to be involved in these developmental processes. m7G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases.Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.

A systematic review and meta-analysis of factors related to non-suicidal self-injury among Chinese adolescents.

BACKGROUND: Over the past several decades the prevalence of adolescent non-suicidal self-injury (NSSI) has been rising steadily. Understanding the factors associated with NSSI is a critical public health concern. The current study aims to explore the critical factors related to NSSI among Chinese adolescents. METHODS: A systematic literature search was conducted to identify the studies meeting our eligibility criteria (published until June 2022) in PubMed, Web of Science, Science Direct, Springer Link, CNKI, VIP, and Wanfang data. The meta-package of R language was used to perform a meta-analysis to compute the pooled effect (r). RESULTS: A total of 59 studies were included in this analysis, with a sample size of 192,546. Twenty-four democratic, personal, and social factors were examined in current study. The pooled effect value (r) has revealed that 23 factors are associated with NSSI behaviors among Chinese adolescents. The factor, Internet addiction, has demonstrated the greatest association with NSSI compared to other factors. CONCLUSION: Consistent with previous studies on adolescent NSSI, findings have demonstrated that a number of demographic, personal, and social factors significantly contribute to NSSI behaviors among Chinese adolescents. Future research on prevention and intervention for adolescent NSSI may benefit from targeting these factors.

Continuous Room-Temperature Spin-Injection Modulation Achieved by Spin-Filtering Competition in Molecular Spin Valves.

Abundant spin-related phenomena that originate from interfaces between ferromagnetic electrodes and molecular semiconductors have greatly enriched research in spintronics, and they are considered promising for realizing novel spintronic functionalities in the future. However, despite great effort, the interfacial effect cannot be precisely controlled to achieve steady and predictable functions, especially at room temperature, and this has gradually become a significant bottleneck in the development of molecular spintronics. In this study, an innovative spin-filtering-competition mechanism is proposed to continuously modulate the interfacial effect in molecular spin valves at room temperature. To form this novel mechanism, the original spin-filtering effect from pure cobalt competes with the newly generated one, which is induced by the bonding effect between cobalt and lithium fluoride. Subsequently, by precisely controlling competition through lithium fluoride coverage on the cobalt surface, continuous modulation of the spin-injection process can be successfully achieved at room temperature. Spin polarization of the injected current and magnetoresistance effect can be actively controlled or their sign can be completely reversed through this novel mechanism. This study provides an innovative approach and theory for precisely controlling spin-related interfacial effects, which may further promote the scientific and technological development of spintronics.

The adaptive market hypothesis and high frequency trading.

This paper uses NASDAQ order book data for the S&P 500 exchange traded fund (SPY) to examine the relationship between one-minute, informational market efficiency and high frequency trading (HFT). We find that the level of efficiency varies widely over time and appears to cluster. Periods of high efficiency are followed by periods of low efficiency and vice versa. Further, we find that HFT activity is higher during periods of low efficiency. This supports the argument that HFTs seek profits and risk reduction by actively processing information, through limit order additions and cancellations, during periods of lower efficiency and revert to more passive market-making and rebate-generation during periods of higher efficiency. These findings support the argument that the adaptive market hypothesis (AMH) is an appropriate description of how prices evolve to incorporate information.

Adoption and effectiveness of de-escalated radiation and endocrine therapy strategies for older women with low-risk breast cancer.

PURPOSE: Recent clinical trials support de-escalation of adjuvant radiation therapy following lumpectomy in some older women with low-risk HR+ breast cancers planning to take endocrine therapy. The adoption of these findings into clinical practice, and the effectiveness of de-escalated therapy in real-world populations, remain under investigation. MATERIALS AND METHODS: We evaluated use of adjuvant radiation therapy and/or endocrine therapy among older women with T1-2 node-negative, HR+ breast cancer in the United States between 2007 and 2011. The study included patients from the Surveillance, Epidemiology and End Results-Medicare linked database and the North Carolina Cancer Information and Population Health Resource database. RESULTS: Radiation therapy was received by 65.5% of patients, with no decrease over time. Older women and those with T2 (compared to T1) tumors were less likely to receive radiation therapy. In propensity-adjusted analyses, both radiation therapy alone (HR 0.75, 95% CI 0.67-0.84) and radiation + endocrine therapy (HR 0.62, 95% CI 0.54-0.69) were associated with significantly lower recurrence risk compared to endocrine therapy alone. Non-adherence to endocrine therapy was common (37%) and similar across groups. With a median follow-up of 48 months (range 13-84), we were not able to detect an association of non-adherence with recurrence risk in endocrine therapy-containing treatment arms. CONCLUSION: Most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors. These findings suggest that while multiple evidence-based treatment options exist in these patients, improvements are needed to ensure that radiation therapy is applied equitably and rationally.

Changes in chronic medication adherence in older adults with cancer versus matched cancer-free cohorts.

OBJECTIVES: A cancer diagnosis can influence medication adherence for chronic conditions by shifting care priorities or reinforcing disease prevention. This study describes changes in adherence to medications for treating three common chronic conditions - diabetes, hyperlipidemia, and hypertension - among older adults newly diagnosed with non-metastatic breast, colorectal, lung, or prostate cancer. METHODS: We identified Medicare beneficiaries aged ≥66 years newly diagnosed with cancer and using medication for at least one chronic condition, and similar cohorts of matched individuals without cancer. To assess medication adherence, proportion of days covered (PDC) was measured in six-month windows starting six-months before through 24 months following cancer diagnosis or matched index date. Generalized estimating equations were used to estimate difference-in-differences (DID) comparing changes in PDCs across cohorts using the pre-diagnosis window as the referent. Analyses were run separately for each cancer type-chronic condition combination. RESULTS: Across cancer types and non-cancer cohorts, adherence was highest for anti-hypertensives (90-92%) and lowest for statins (77-79%). In older adults with colorectal and lung cancer, adherence to anti-diabetics and statins declined post-diagnosis compared with the matched non-cancer cohorts, with estimates ranging from a DID of -2 to -4%. In older adults with breast and prostate cancer cohorts, changes in adherence for all medications were similar to non-cancer cohorts. CONCLUSION: Our findings highlight variation in medication adherence by cancer type and chronic condition. As many older adults with early stage cancer eventually die from non-cancer causes, it is imperative that cancer survivorship interventions emphasize medication adherence for other chronic conditions.

Adding a recyclable amendment to facilitate sewage sludge biodrying and reduce costs.

Finding an economical amendment, available in a steady supply, is needed to support the biodrying industrialization. This research developed a recyclable biodrying amendment (RBA) to condition the biodrying of sewage sludge. The pilot-scale treatment (TR), which included the addition of equivalent weights of RBA and sawdust as amendments, resulted in a higher pile temperature and longer thermophilic phase compared to the control (TC), which used only sawdust as an amendment. The final moisture content levels were below 50% with both TR and TC. The heat use efficiency for water evaporation was 72.2% and 73.0% in TR and TC, respectively. The activity of α-amylase and cellulose 1,4-ß-cellobiosidase increased during the thermophilic phase, while the activity of endo-1,4-ß-glucanase and endo-1,4-ß-xylanase decreased during the thermophilic phase with both TR and TC. The fourier-transform infrared spectra indicated that adding the RBA resulted in good biodegradability of the lipids, proteins, and polysaccharides. The humic acid to fulvic acid ratio in TR and TC increased from 0.33 (TR) and 0.35 (TC) on day 0-0.46 (TR) and 0.45 (TC) on day 21, indicating the humification process. The RBA recovery rate was 95.6% and can be reused. These findings highlight that adding RBA showed satisfactory biodrying performance, reduced the amendment cost, and the biodrying product could be incinerated without energy deficit.

Breastfeeding duration of different age groups and its associated factors among Chinese women: a cross-sectional study.

Background: The current situation of breastfeeding in China has been discussed in many articles, and a declining trend of breastfeeding duration has been confirmed. The associations between various socioeconomic, reproductive factors and breastfeeding duration have been discussed as well. However, there remains a lack of evidence on breastfeeding duration amongst different age groups. Methods: Data was extracted from the baseline of a large cohort study: a sample of 300,000 adult women born in the 1930s' through 1970s' from 10 geographically distinct regions was obtained. The breastfeeding duration was assumed by breastfeeding duration of the first child. Different age groups were categorized by 10-year age groups, and they were born in 1930-1938, 1939-1948, 1949-1958, 1959-1968, and 1969-1974. Multivariable linear regression was used to evaluate the associations between breastfeeding duration and sociodemographic, and reproductive factors (i.e.: different age groups, education, household size, use of oral contraceptive pills, age at menarche, and age at first birth). Results: The mean breastfeeding duration (Standard Deviation) of women born in 1930-1938, 1939-1948, 1949-1958, 1959-1968, and 1969-1974 were 15.4 (9.2), 14.8 (8.2), 14.7 (8.9), 12.8 (7.2), 13.1 (7.2) months, respectively. Younger age groups, higher levels of education, and use of oral contraceptive pills were negatively associated with breastfeeding duration. In particular, the negative association with higher levels of education (for urban regions: ßmiddle school = - 1.3, ßhigh school & above = - 1.6; for rural regions: ßmiddle school = - 0.6, ßhigh school & above = - 1.2; all p < 0.0001) was found significant in both rural and urban areas, household size (ß = - 0.1, p < 0.0001) and age at first birth (ß = - 0.2, p < 0.0001) were negatively associated with breastfeeding duration only in urban areas, but were all positively associated with breastfeeding duration in rural areas. Conclusions: This research demonstrated that, among Chinese women, younger age groups and higher levels of education were negatively associated with breastfeeding duration. Considering the declining trend of breastfeeding duration in China, healthcare providers need to continue advocating for breastfeeding practices. We also call for collaboration with various sectors and concerned groups to actions that promote breastfeeding-friendly environment and measures.

An updated systematic review of the cost-effectiveness of therapies for metastatic breast cancer.

PURPOSE: The goal of this systematic review is to provide an update to the review by Pouwels et al. by conducting a systematic review and an assessment of the reporting quality of the economic analyses conducted since 2014. METHODS: This systematic review identified published articles focused on metastatic breast cancer treatment using the Medline/PubMed and Scopus databases and the following search criteria: (((cost effectiveness[MeSH Terms]) OR (cost effectiveness) OR (cost-effectiveness) OR (cost utility) OR (cost-utility) OR (economic evaluation)) AND (("metastatic breast cancer") OR ("advanced breast cancer"))). The reporting quality of the included articles was evaluated using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Of the 256 identified articles, 67 of the articles were published after October 2014 when the prior systematic review stopped its assessment (Pouwels et al. in Breast Cancer Res Treat 165:485-498, 2017). From the 67 articles, we narrowed down to include 17 original health economic analyses specific to metastatic or advanced breast cancer. These articles were diverse with respect to methods employed and interventions included. CONCLUSION: Although each of the articles contributed their own analytic strengths and limitations, the overall quality of the studies was moderate. The review demonstrated that the vast majority of the reported incremental cost-effectiveness ratios exceeded the typically employed willingness to pay thresholds used in each country of analysis. Only three of the reviewed articles studied chemotherapies rather than treatments targeting either HER2 or hormone receptors, demonstrating a gap in the literature.

Occurrence and risk assessment of potentially toxic elements and typical organic pollutants in contaminated rural soils.

The residual levels and risk assessment of several potentially toxic elements (PTEs), phthalate esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs) in rural soils near different types of pollution sources in Tianjin, China, were studied. The soils were found to be polluted to different extents with PTEs, PAEs and PAHs from different pollution sources. The soil concentrations of chromium (Cr), nickel (Ni), di-n-butyl phthalate (DnBP), acenaphthylene (Any) and acenaphthene (Ane) were higher than their corresponding regulatory reference limits. The health risk assessment model used to calculate human exposure indicates that both non-carcinogenic and carcinogenic risks from selected pollutants were generally acceptable or close to acceptable. Different types of pollution sources and soil physicochemical properties substantially affected the soil residual concentrations of and risks from these pollutants. PTEs in soils collected from agricultural lands around industrial and residential areas and organic pollutants (PAEs and PAHs) in soils collected from agricultural areas around livestock breeding were higher than those from other types of pollution sources and merit long-term monitoring.

The relationship of travel distance with cystectomy access and outcomes.

PURPOSE: Regionalization of care and travel distance may result in unintended consequences for complex surgery such as cystectomy. Our objective was to evaluate effect of differential distance on cystectomy receipt among patients with muscle-invasive bladder cancer (MIBC) and investigate the association between travel distance and cystectomy outcomes such as readmission. METHODS: Using a linked data resource combining the NC Central Cancer Registry with claims data from Medicare, Medicaid, and private insurance plans, we included 736 patients with MIBC and 1,082 who underwent cystectomy. To evaluate access, differential distance was calculated as the difference between the nearest urologist and nearest cystectomy provider. To assess outcomes, logistic regression was used to evaluate rehospitalization and major complications, and Cox proportional hazards model for survival analysis. RESULTS: To evaluate access and outcomes, 736 patients with MIBC and 1,082 patients undergoing cystectomy were evaluated, respectively. Overall, 29% (211 of 736) with MIBC underwent cystectomy. Differential distance was not a predictor of cystectomy receipt (odds ratio = 1.0; 95% CI: 1.00, 1.01). Among patients undergoing cystectomy, travel distance from cystectomy provider was not a significant predictor of 30- or 31 to 90day readmissions (odds ratio = 1.0; 95% CI: 1.00, 1.00) although patients who lived further from their cystectomy provider were more likely to be readmitted to a nonindex hospital (P<0.001) when controlling for other factors. Although travel distance did not have a significant effect on overall survival, patients readmitted between 31 to 90days had worse overall survival (P<0.0001). CONCLUSIONS: The additional distance needed to reach a cystectomy provider did not predict receipt of surgery for MIBC. Furthermore, travel distance from cystectomy provider was not a significant predictor for subsequent readmission after cystectomy and did not affect overall survival.

Comparative Toxicity and Effectiveness of Trastuzumab-Based Chemotherapy Regimens in Older Women With Early-Stage Breast Cancer.

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2-positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score-matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer-specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab. We did not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate.

Clinical Benefits Associated With Medicaid Coverage Before Diagnosis of Gynecologic Cancers.

PURPOSE: Many low-income patients enroll in Medicaid at the time of cancer diagnosis, which improves survival outcomes. Medicaid enrollment before cancer diagnosis may confer additional benefits. Our objective was to compare stage at diagnosis and overall mortality between women with and without Medicaid enrollment before gynecologic cancer diagnosis. METHODS AND MATERIALS: Women younger than 65 years with a gynecologic cancer (2003 to 2008) were identified through the North Carolina Central Cancer Registry and linked to state Medicaid enrollment files. Those with and without Medicaid enrollment within 6 months before diagnosis were identified. Propensity matching was used to balance the exposure groups. Stage at diagnosis was evaluated by using logistic regression, and all-cause mortality was assessed with Cox proportional hazard models. RESULTS: Of 564 women, one half (n = 282) had prediagnosis Medicaid enrollment. Disease sites included the cervix (44%), uterus (25%), ovary (26%), and vulva/vagina (5%). More than one half (51%) of cancers were advanced stage. Women without prediagnosis Medicaid had an increased odds of advanced-stage disease (hazard ratio, 1.46; 95% CI, 1.03 to 2.05). Crude survival outcomes differed significantly between the groups; however, when adjusted for stage at diagnosis, lack of prediagnosis Medicaid coverage had a hazard ratio of 1.19 (95% CI, 0.92 to 1.53). CONCLUSION: Medicaid enrollment before gynecologic cancer diagnosis is associated with an earlier stage at presentation. Given the existence of a cervical cancer screening program in North Carolina and lack of Medicaid expansion, these data suggest that screening programs alone are not sufficient to counteract the delay in diagnosis that is common for uninsured individuals.

Referral patterns between high- and low-volume centers and associations with uterine cancer treatment and survival: a population-based study of Medicare, Medicaid, and privately insured women.

BACKGROUND: High-volume center surgery and gynecologic oncology care are associated with improved outcomes for women with uterine cancer. Referral patterns, from biopsy through to chemotherapy, may have patients interacting with high-volume centers for all, a portion, or none of their care. The relative frequency, the underlying factors that contribute to referral, and the potential impact of these referral patterns on treatment outcomes are unknown. OBJECTIVE: We sought to analyze the referral patterns and subsequent impact of care sites on treatment for women with high- and low-risk uterine cancer. STUDY DESIGN: This is a population-based retrospective cohort study of uterine cancer cases from 2004 through 2009 in North Carolina. Using state cancer registry files linked to Medicare, Medicaid, and private payer insurance claims, we analyzed referral and treatment patterns by annual surgical volume (high ≥12/y). We examined clinical and demographic factors associated with referral and used modified Poisson regression to evaluate risk of referral, lymphadenectomy, and chemotherapy. Stratified Kaplan-Meier plots and Cox proportional hazard models were used to examine survival. RESULTS: A total of 2053 women were analyzed, including 34% (n = 677) with grade 3 histology. Of 1630 (80%) women with preoperative biopsies, referral patterns (biopsy to surgery) were: low volume to high volume (n = 652, 40%), followed by high volume to high volume (n = 605, 37%), then low volume to low volume (n = 318, 20%), and the rare high volume to low volume (n = 50, 3%). Women retained in low-volume centers after biopsy were older, were less likely to have private insurance, and had more comorbidities. High-risk histology (aRR, 1.14; 95% confidence interval, 1.04-1.25) was positively associated with referral, while Medicaid insurance was negatively associated with referral (aRR, 0.64; 95% confidence interval, 0.42-0.96). Most women (74%, n = 1557) had surgery at high-volume centers. Lymphadenectomy was less likely at low-volume centers (aRR, 0.71; 95% confidence interval, 0.64-0.77). Similarly, for high-risk patients, the relationship between low-volume center surgery and subsequent chemotherapy was aRR, 0.71 (95% confidence interval, 0.48-1.02). Of 290 women who received chemotherapy, the referral patterns (surgery to chemotherapy) were: high volume-all (high volume to high volume), high volume-hybrid (high volume to low volume, or low volume to high volume), and high volume-none (low volume to low volume). In all, 36% (n = 104/290) received chemotherapy at a low-volume center, the majority (68%, n = 71/104) of whom were referred from high-volume centers after surgery. Crude, unadjusted mortality risk of chemotherapy recipients differed by referral pattern (surgery to chemotherapy): high volume-all patients (hazard ratio, 1.0; referent), followed by high volume-hybrid (hazard ratio, 1.33; 95% confidence interval, 0.93-1.91) then high volume-none patients (RR, 1.95; 95% confidence interval, 1.24-3.08). CONCLUSION: Most women with uterine cancer treated at high-volume centers arrive through referral, which is affected by age and type of insurance, in addition to histology. For high-risk women who require chemotherapy, survival may be related to the extent of treatment received at high-volume centers.

Disparities in Use of Human Epidermal Growth Hormone Receptor 2-Targeted Therapy for Early-Stage Breast Cancer.

PURPOSE: Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. METHODS: We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. RESULTS: Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). CONCLUSION: Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.

Gynecologic cancer outcomes in the elderly poor: A population-based study.

BACKGROUND: Adults aged ≥65 years who are dually enrolled in Medicare and Medicaid are an at-risk group in health care. However, to the best of the authors' knowledge, the outcomes of women with gynecologic cancers in this population are unknown. METHODS: The current study was a population-based cohort study of North Carolina state cancer registry cases of uterine, ovarian, cervical, and vulvar/vaginal cancers (2003-2009), with linked enrollment in Medicare and state Medicaid. Outcomes of all-cause mortality and stage of disease at the time of diagnosis were analyzed as a function of enrollment status using multivariate analysis and survival curves. RESULTS: Of 4522 women aged ≥65 years (3702 of whom were enrolled in Medicare [82%] and 820 of whom were dually enrolled [18%]), there were 2286 cases of uterine (51%), 1587 cases of ovarian (35%), 302 cases of cervical (7%), and 347 cases of vulvar/vaginal (8%) cancers. Dual enrollees had increased all-cause mortality overall (adjusted hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.19-1.49), and within each cancer site (uterine: aHR, 1.22 [95% CI, 1.02-1.47]; ovarian: aHR, 1.25 [95% CI, 1.05-1.49]; cervical: aHR, 1.34 [95% CI, 0.96-1.87]; and vulvar/vaginal: aHR, 1.93 [95% CI, 1.36-2.72]). Increased odds of advanced-stage disease at the time of diagnosis among dual enrollees was only present in patients with uterine cancer (adjusted odds ratio, 1.38; 95% CI, 1.06-1.79). Stratified survival curves demonstrated the strongest disparities among women with early-stage uterine and early-stage vulvar/vaginal cancers. CONCLUSIONS: Women aged ≥65 years who were dually enrolled in Medicare and Medicaid were found to have an overall 34% increase in all-cause mortality after diagnosis with a gynecologic cancer compared with the non-dually enrolled Medicare population. Women with early-stage uterine and vulvar/vaginal cancers appeared to have the most disparate outcomes. Because these malignancies are generally curable, they have the most potential for benefit from targeted interventions.