"Pathways": A hope-enhancing intervention for patients undergoing treatment for advanced lung cancer.

OBJECTIVE: Observational data suggest hope is associated with the quality of life and survival of people with cancer. This trial examined the feasibility, acceptability, and preliminary outcomes of "Pathways," a hope intervention for people in treatment for advanced lung cancer. METHODS: Between 2020 and 2022, we conducted a single-arm trial of Pathways among participants who were 3-12 weeks into systemic treatment. Pathways consisted of two individual sessions delivered during infusions and three phone calls in which participants discussed their values, goals, and goal strategies with a nurse or occupational therapist. Participants completed standardized measures of hope and goal interference pre- and post-intervention. Feasibility was defined as ≥60% of eligible patients enrolling, ≥70% of participants completing three or more sessions, ≥70% of participants completing post-assessments, and mean acceptability ratings ≥7 out of 10 on intervention relevance, helpfulness, and convenience. Linear regression fixed effects models with covariates modeled pre-post changes in complete case analysis and multiple imputation models. RESULTS: Fifty two participants enrolled: female (59.6%), non-Hispanic White (84.6%), rural (75.0%), and with low educational attainment (51.9% high school degree or less). Except for enrollment (54%), feasibility and acceptability markers were surpassed (77% adherence, 77% retention, acceptability ratings ≥8/10). There was moderate improvement in hope and goal interference from pre-to post-intervention (d = 0.51, p < 0.05 for hope; d = -0.70, p < 0.005 for goal interference). CONCLUSIONS: Strong feasibility, acceptability, and patient-reported outcome data suggest Pathways is a promising intervention to increase hope and reduce cancer-related goal interference during advanced lung cancer treatment.

Palliative care use and utilization determinants among patients treated for advanced stage lung cancer care in the community and academic medical setting.

PURPOSE: Despite clinical guidelines, palliative care is underutilized during advanced stage lung cancer treatment. To inform interventions to increase its use, patient-level barriers and facilitators (i.e., determinants) need to be characterized, especially among patients living in rural areas or those receiving treatment outside academic medical centers. METHODS: Between 2020 and 2021, advanced stage lung cancer patients (n = 77; 62% rural; 58% receiving care in the community) completed a one-time survey assessing palliative care use and its determinants. Univariate and bivariate analyses described palliative care use and determinants and compared scores by patient demographic (e.g., rural vs. urban) and treatment setting (e.g., community vs. academic medical center) factors. RESULTS: Roughly half said they had never met with a palliative care doctor (49.4%) or nurse (58.4%) as part of cancer care. Only 18% said they knew what palliative care was and could explain it; 17% thought it was the same as hospice. After palliative care was distinguished from hospice, the most frequently cited reasons patients stated they would not seek palliative care were uncertainty about what it would offer (65%), concerns about insurance coverage (63%), difficulty attending multiple appointments (60%), and lack of discussion with an oncologist (59%). The most common reasons patients stated they would seek palliative care were a desire to control pain (62%), oncologist recommendation (58%), and coping support for family and friends (55%). CONCLUSION: Interventions should address knowledge and misconceptions, assess care needs, and facilitate communication between patients and oncologists about palliative care.

Impact of relative dose intensity on pathologic complete response in human epidermal growth factor receptor 2 positive breast cancer patients receiving neoadjuvant TCHP.

PURPOSE: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. METHODS: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. RESULTS: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. CONCLUSIONS: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

A Daily Assessment Study of Smoking Cessation After a Head and Neck Cancer Diagnosis.

INTRODUCTION: This intensive longitudinal study describes key events in the process of smoking cessation after a new head and neck cancer (HNC) diagnosis. Prior longitudinal studies show some cancer patients quit, while others continue to smoke, but details about the pattern in which these discrete outcomes arise are scarce. This study is meant to help rectify this gap in the literature. AIMS AND METHODS: Participants were 42 HNC patients who reported current smoking at enrollment. Participants were recruited from an outpatient oncology clinic and completed a baseline questionnaire prior to begin a 30-day daily assessment. RESULTS: Few participants (9.52%) achieved 30-day continuous abstinence from smoking. On average, participants reported 9.64 ± 11.93 total days of abstinence. Nearly, all (94.44%, n = 34) participants made at least one quit attempt, with an average of 16.94 ± 11.30 quit attempt days. Fewer participants were able to achieve a 24-hour quit attempt (52.78%, n = 19), with a corresponding average of 5.50 ± 8.69 24-hour days. The median time to first 24-hour quit attempt was 13 days after enrollment. Based on smoking behavioral patterns, participants were categorized into five groups, the most common being "persistent attempters," which involved unsuccessful quit attempts throughout the study. Only 45% of participants (n = 19) used evidence-based treatment, the most common being cessation medication. CONCLUSIONS: This intensive longitudinal study found that cancer diagnosis can spur a lot of efforts to quit smoking. Unfortunately, this study suggests that many quit attempts are short lived, possibly a result of an absence or insufficient use of evidence-based treatments. IMPLICATIONS: For adults who are current smokers at the time of cancer diagnosis, there is a high likelihood of persistent cigarette smoking and use of other tobacco products in the weeks and months after a cancer diagnosis. Furthermore, this study shows that while a lot of quit attempts may occur, few are successful, which may be partly attributable to the low use of evidence-based tobacco treatment. Future research with cancer patients should aim to identify predictors of quit attempts and abstinence as well as treatment utilization.

Using Implementation Science to Disseminate a Lung Cancer Screening Education Intervention Through Community Health Workers.

National lung cancer screening with low dose computed tomography (LDCT) uptake is suboptimal. One factor contributing to slow uptake is lack of awareness. Trained Community Health Workers (CHWs) may be effective in increasing lung cancer screening awareness among disparate populations, however little is known about the processes necessary to scale an intervention for implementation by CHWs in a new area. We examined implementation processes with the RE-AIM framework and pilot tested a CHW-delivered lung cancer education intervention based on the Health Belief Model. We measured pre-post participant knowledge, attitudes and beliefs regarding cancer screening, lung cancer stigma, and intent to obtain LDCT screening. We used community-engaged strategies to collaborate with a local health system, to identify CHWs. CHWs were trained to recruit participants and deliver the one-session lung cancer education intervention. Seven CHWs and eight community sites participated. Participants (n = 77) were female (53%) primarily low income (62.9%); tobacco use was high (36.9%). Post intervention changes in lung cancer screening knowledge (p = < .0001), attitudes regarding lung cancer screening benefit (p = .034) and lung cancer stigma. (p = .024) We learned important lessons that will be useful in subsequent scaling. Collaborating with a local health system is a promising method to disseminate a lung cancer screening education intervention.

Web-Based Contingency Management for Adolescent Tobacco Smokers: A Clinical Trial.

INTRODUCTION: Adolescence is a critical time when the majority of tobacco users initiate smoking. Contingency management for adolescent smoking cessation has shown promise in previous studies, but efficacy following removal of contingencies is not well understood. This study examined a remote form of contingency management among non-treatment-seeking adolescent smokers. METHODS: Participants (N = 127) submitted breath carbon monoxide (CO) three times daily throughout a 42-day program. For this randomized trial, participants in the active condition (n = 63) were reinforced for providing CO measurements on schedule and below a set criterion, whereas those in the control condition (n = 64) were reinforced for providing CO measurements on schedule. Self-reported smoking and urinary cotinine levels were collected at several timepoints. RESULTS: Active condition showed greater within-group reductions in CO levels relative to control condition, but not at 3- or 6-month follow-up. Active condition reported significantly less smoking during treatment compared to control condition, but not at follow-up. There were no significant differences for urinary cotinine. Overall treatment adherence was low, with only 37% and 51% of possible CO samples being submitted among active and control, respectively. Poor treatment adherence may explain the disparity between CO and cotinine results, and poor follow-up treatment efficacy. CONCLUSIONS: This study replicates feasibility of a remote form of contingency management for adolescent smoking. CO results suggest active condition reduced smoking within group, but treatment adherence and posttreatment efficacy was poor. Future research should focus on increasing adherence for this type of program among adolescent smokers. IMPLICATIONS: This study demonstrates feasibility of a remote form of contingency management therapy for smoking cessation among adolescents, while providing posttreatment efficacy data. Within-group efficacy of this form of treatment is suggested, but treatment adherence and follow-up efficacy were poor. This study underscores the need for further development of contingency management therapy for adolescent smoking cessation, which emphasizes better treatment adherence and posttreatment efficacy.

Outcomes in surgically resectable oropharynx cancer treated with transoral robotic surgery versus definitive chemoradiation.

PURPOSE: Optimal treatment strategies for the management of oropharyngeal squamous cell carcinoma (OPSCC) remain unclear. The objective of this study is to examine the role of transoral robotic surgery (TORS) on functional and treatment outcomes. MATERIALS AND METHODS: A retrospective review of patients with OPSCC (tonsil/base of tongue) who underwent TORS with neck dissection± adjuvant therapy between January 2011 to December 2016 were compared to a stage matched cohort of patients treated with primary chemoradiation. Demographic, treatment, and outcome data were collected. RESULTS: 54 patients received primary chemoradiation and 65 patients (surgical group) received TORS ± adjuvant therapy for clinically staged disease meeting study criteria. 25% (N = 17) were treated with surgery alone. The remainder of the surgical group received postoperative radiation (N = 48), half of which received adjuvant chemotherapy (N = 24) in addition to radiation. 63% (N = 41) of the patients did not have risk factors for chemotherapy. No differences in overall or disease free survival were observed with TORS compared to chemoradiation (p = 0.9), although Charlson Comorbidity Index (CCI) was higher in the surgical group (p = 0.01). The strongest predictor of prolonged gastrostomy tube use was not treatment, but rather co-morbidity (p = 0.03), with no significant differences beyond 12 months. CONCLUSION: Although no significant survival differences were observed across treatment groups, this was maintained despite increased comorbidity index in the surgical patients. Given the ability to de-escalate and/or eliminate adjuvant therapy, particularly in a less healthy population, TORS would appear to be the viable treatment option it has become.

Estimation of exposure distribution adjusting for association between exposure level and detection limit.

In environmental exposure studies, it is common to observe a portion of exposure measurements to fall below experimentally determined detection limits (DLs). The reverse Kaplan-Meier estimator, which mimics the well-known Kaplan-Meier estimator for right-censored survival data with the scale reversed, has been recommended for estimating the exposure distribution for the data subject to DLs because it does not require any distributional assumption. However, the reverse Kaplan-Meier estimator requires the independence assumption between the exposure level and DL and can lead to biased results when this assumption is violated. We propose a kernel-smoothed nonparametric estimator for the exposure distribution without imposing any independence assumption between the exposure level and DL. We show that the proposed estimator is consistent and asymptotically normal. Simulation studies demonstrate that the proposed estimator performs well in practical situations. A colon cancer study is provided for illustration. Copyright © 2017 John Wiley & Sons, Ltd.

Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii.

In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations, including LPS. However, the physiological role of IFN-γ production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b(+) cells suggested that IFN-γ production by microglia, which is the only CD11b(+) cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-γ produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii.

Delay discounting and self-reported impulsivity in adolescent smokers and nonsmokers living in rural Appalachia.

Background and Objectives This study evaluated whether impulsivity (delay discounting and BIS-11-A) is associated with adolescent smoking status in a region with strong environmental risk factors for smoking. Methods Forty-two adolescent smokers and nonsmokers from rural Appalachia completed discounting and self-reported impulsivity assessments. Results The BIS-11-A, but not the measure of discounting, was associated with smoking status; however, neither assessment predicted smoking status once parent/best-friend smoking variables were statistically accounted for. Discussion and Conclusions In regions with strong environmental risk factors for smoking, delay discounting may play a more limited role in risk of initiation. Scientific Significance Helps to better define impulsivity as risk factors for smoking in relation to familial and broader cultural variables.

A rural Appalachian faith-placed smoking cessation intervention.

Although health promotion programming in faith institutions is promising, most faith-based or placed health projects focus on diet, exercise, or cancer screening and many have been located in urban environments. This article addresses the notable absence of faith programming for smoking cessation among underserved rural US residents who experience tobacco-related health inequities. In this article, we describe our faith-oriented smoking cessation program in rural Appalachia, involving 590 smokers in 26 rural churches randomized to early and delayed intervention groups. We present three main themes that account for participants' positive evaluation of the program; the program's ability to leverage social connections; the program's convenience orientation; and the program's financial support for smoking cessation. We also present themes on the roles of faith and church in smoking cessation programming, including some mixed perceptions on smoking stigma and comfort in church settings; challenges in faith-placed smoking cessation recruitment; and the positive perception of such programming by church leaders. We conclude that faith-placed smoking cessation programs offer great potential, although they must be administered with great sensitivity to individual and community norms.

A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure.

Fulvestrant, which degrades ER, is used after AI failure in metastatic breast cancer but resistance develops quickly. We hypothesized that using everolimus to inhibit mTOR, a key signaling pathway in endocrine resistance, may delay fulvestrant resistance in patients and thus improve its efficacy. We conducted a phase II trial of combined fulvestrant and everolimus in postmenopausal women with disease progression or relapse after an AI. Primary endpoint was time to progression (TTP) and secondary endpoints included objective response rate, clinical benefit rate (CBR), safety, and biomarker correlates. Tumor blocks were collected and biopsy of accessible tumor was done for future biomarker analysis. Of 33 patients enrolled two were ruled ineligible after enrollment and were excluded from study analysis, for a total of 31 evaluable patients. Median age was 54 years (range 45-85). Prior therapy included tamoxifen (81 %), chemotherapy (71 %), with 26 % of patients having received 3 or more endocrine agents. Median TTP was 7.4 months (95 % CI 1.9-12.1) with an objective response rate of 13 % and CBR of 49 %. Of particular note, 32 % of patients exhibited de novo resistance to study treatment with disease progression as their best response. Most common adverse events (AEs) were elevated AST (87 %) and ALT (77 %), anemia (74 %), hyperglycemia (71 %), and hypercholesterolemia (68 %). Prominent clinical toxicities were mucositis (58 %), weight loss (48 %), and rash (42 %). Most AEs were grade 1 or 2 and largely reversible with infrequent need for everolimus dose reduction. To conclude, everolimus plus fulvestrant is effective after AI failure in heavily pretreated metastatic ER-positive breast cancer and has manageable toxicity. Further study of this combination is warranted in randomized studies. Since not all patients experience benefit, and in view of potential toxicities, biomarker examination is critical to help select patients most likely to benefit from this strategy in future studies.

Effectiveness of a primary care practice intervention for increasing colorectal cancer screening in Appalachian Kentucky.

OBJECTIVE: This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. METHODS: Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. RESULTS: A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). CONCLUSIONS: Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy.

Cervical cancer screening: exploring Appalachian patients' barriers to follow-up care.

This article describes a community-based Patient Navigation (PN) project conducted to identify potential barriers to seeking follow-up cervical cancer care in southeastern Kentucky. Patient navigators (PNs) were placed in cervical cancer programs within county public health departments where they interviewed patients about their perceived barriers to seeking follow-up care after receiving a positive Pap test result. Participants identified various potential barriers at three levels: the individual/personal level, the health care system level and the community/environmental level. One identified barrier that was unique to this study was a lack of consistency between follow-up recommendations and follow-up guidelines for patients under age 21. Implications are discussed.

A Social Media-Delivered Melanoma Prevention Program for Young Women Engaged in Frequent UV Tanning: Protocol for a Randomized Controlled Trial.

BACKGROUND: Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. OBJECTIVE: This study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. METHODS: Participants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. RESULTS: This project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. CONCLUSIONS: This trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals' everyday routines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56562.

Piloting a Patient Tool to Aid Palliative Care Referrals during Advanced Lung Cancer Treatment.

CONTEXT: Patient misperceptions are a strong barrier to early palliative care discussions and referrals during advanced lung cancer treatment. OBJECTIVES: We developed and tested the acceptability of a web-based patient-facing palliative care education and screening tool intended for use in a planned multilevel intervention (i.e., patient, clinician, system-level targets). METHODS: We elicited feedback from advanced lung cancer patients (n = 6), oncology and palliative care clinicians (n = 4), and a clinic administrator (n = 1) on the perceived relevance of the intervention. We then tested the prototype of a patient-facing tool for patient acceptability and preliminary effects on patient palliative care knowledge and motivation. RESULTS: Partners agreed that the intervention-clinician palliative care education and an electronic health record-integrated patient tool-is relevant and their feedback informed development of the patient prototype. Advanced stage lung cancer patients (n = 20; age 60 ± 9.8; 40% male; 70% with a technical degree or less) reviewed and rated the prototype on a five-point scale for acceptability (4.48 ± 0.55), appropriateness (4.37 ± 0.62), and feasibility (4.43 ± 0.59). After using the prototype, 75% were interested in using palliative care and 80% were more motivated to talk to their oncologist about it. Of patients who had or were at risk of having misperceptions about palliative care (e.g., conflating it with hospice), 100% no longer held the misperceptions after using the prototype. CONCLUSION: The palliative care education and screening tool is acceptable to patients and may address misperceptions and motivate palliative care discussions during treatment.

Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults.

NK cells are essential for health, yet little is known about human NK turnover in vivo. In both young and elderly women, all NK subsets proliferated and died more rapidly than T cells. CD56(bright) NK cells proliferated rapidly but died relatively slowly, suggesting that proliferating CD56(bright) cells differentiate into CD56(dim) NK cells in vivo. The relationship between CD56(dim) and CD56(bright) proliferating cells indicates that proliferating CD56(dim) cells both self-renew and are derived from proliferating CD56(bright) NK cells. Our data suggest that some dying CD56(dim) cells become CD16(+)CD56(-) NK cells and that CD16(-)CD56(low) NK cells respond rapidly to cellular and cytokine stimulation. We propose a model in which all NK cell subsets are in dynamic flux. About half of CD56(dim) NK cells expressed CD57, which was weakly associated with low proliferation. Surprisingly, CD57 expression was associated with higher proliferation rates in both CD8(+) and CD8(-) T cells. Therefore, CD57 is not a reliable marker of senescent, nonproliferative T cells in vivo. NKG2A expression declined with age on both NK cells and T cells. Killer cell Ig-like receptor expression increased with age on T cells but not on NK cells. Although the percentage of CD56(bright) NK cells declined with age and the percentage of CD56(dim) NK cells increased with age, there were no significant age-related proliferation or apoptosis differences for these two populations or for total NK cells. In vivo human NK cell turnover is rapid in both young and elderly adults.

Mobile mammography in underserved populations: analysis of outcomes of 3,923 women.

Mobile health units are increasingly utilized to address barriers to mammography screening. Despite the existence of mobile mammography outreach throughout the US, there is a paucity of data describing the populations served by mobile units and the ability of these programs to reach underserved populations, address disparities, and report on outcomes of screening performance. To evaluate the association of variables associated with outcomes for women undergoing breast cancer screening and clinical evaluation on a mobile unit. Retrospective analysis of women undergoing mammography screening during the period 2008-2010. Logistic regression was fitted using generalized estimating equations to account for potential repeat annual visits to the mobile unit. In total, 4,543 mammograms and/or clinical breast exams were conducted on 3,923 women with a mean age of 54.6, 29 % of whom had either never been screened or had not had a screening in 5 years. Age < 50 years, lack of insurance, Hispanic ethnicity, current smoking, or having a family relative (<50 years of age) with a diagnosis of cancer were associated with increased odds of a suspicious mammogram finding (BIRADS 4,5,6). Thirty-one breast cancers were detected. The mobile outreach initiative successfully engaged many women who had not had a recent mammogram. Lack of insurance and current smoking were modifiable variables associated with abnormal screens requiring follow up.

Weighted mean difference statistics for paired data in the presence of missing values.

Missing data is a common issue in many biomedical studies. Under a paired design, some subjects may have missing values in either one or both of the conditions due to loss of follow-up, insufficient biological samples, etc. Such partially paired data complicate statistical comparison of the distribution of the variable of interest between the two conditions. In this article, we propose a general class of test statistics based on the difference in weighted sample means without imposing any distributional or model assumption. An optimal weight is derived from this class of tests. Simulation studies show that our proposed test with the optimal weight performs well and outperforms existing methods in practical situations. Two cancer biomarker studies are provided for illustration.

Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment.

The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study we compared functional properties of stem and stromal cells between the strains, and delineated the boundary of the B6.SJL congenic interval. We identified a 25% reduction in homing efficiency, 3.8-fold reduction in transplantable long-term hematopoietic stem cells (LT-HSCs), a 5-fold reduction in LT-HSCs capable of 24-hour homing, and a cell-intrinsic engraftment defect of 30% to 50% in B6.SJL-derived bone marrow cells relative to B6-derived cells. These functional differences were independent of stem cell number, cycling, or apoptosis. Genotypic analysis revealed a 42.1-mbp congenic interval in B6.SJL including 306 genes, and at least 124 genetic polymorphisms. Moreover, expression profiling revealed 288 genes differentially expressed between nonhematopoietic stromal cells of the 2 strains. These results indicate that polymorphisms between the B6 and SJL genotype within the B6.SJL congenic interval influence HSC engraftment and result in transcriptional variation within bone marrow stroma.