Residential proximity to oil and gas developments and childhood cancer survival.

BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers. METHODS: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders. RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances. CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.

Latino Enclaves and Healthcare Accessibility: An Ecologic Study Across Five States.

BACKGROUND: Hispanic or Latino populations (hereafter, "Latinos") are a rapidly expanding U.S. demographic and have documented inequities in preventable diseases and conditions. Many Latinos reside in ethnic enclaves, and understanding the context and healthcare accessibility within these places is critical. OBJECTIVE: This study described the neighborhood social and built environment attributes of Latino enclaves and evaluated associations between enclaves and geographic healthcare accessibility. DESIGN: Cross-sectional ecologic analysis. SUBJECTS: Our unit of analysis was all neighborhoods (n ~ 20,000 census tracts) in California, Florida, New Jersey, New York, and Texas in years 2000 and 2010. MAIN MEASURES: The primary exposure of interest, "Latino enclaves," was defined using neighborhood-level data on the percentage of Latino residents, foreign-born Latinos, Spanish speakers with limited English proficiency, and linguistically isolated Spanish-speaking households. The primary outcome was a neighborhood-level measure of geographic healthcare accessibility of primary care physicians, which accounted for both the supply of physicians and population demand for healthcare (i.e., population size within driving distance). RESULTS: Approximately 30% of neighborhoods were classified as Latino enclaves, 87% of which were enclaves in both 2000 and 2010. Compared with non-enclaves, Latino enclaves had more markers of structural disadvantage including having higher proportions of poverty, uninsured individuals, crowded housing, and higher crime scores. Results from multivariable models suggest that more culturally distinct neighborhoods (i.e., higher enclave score) had lower healthcare accessibility, though when stratified, this association persisted only in high (≥ 20%) poverty neighborhoods. CONCLUSION: This study highlights several neighborhood structural disadvantages within Latino enclaves, including higher poverty, uninsured individuals, and crime compared to non-enclave neighborhoods. Moreover, our findings point to the need for interventions aimed at improving healthcare accessibility particularly within socioeconomically disadvantaged Latino enclaves. Addressing these inequities demands multifaceted approaches that consider both social and structural factors to ensure equitable healthcare access for Latino populations.

Geographic Accessibility and Completion of Initial Low-Dose CT-Based Lung Cancer Screening in an Urban Safety-Net Population.

BACKGROUND: Recent modifications to low-dose CT (LDCT)-based lung cancer screening guidelines increase the number of eligible individuals, particularly among racial and ethnic minorities. Because these populations disproportionately live in metropolitan areas, we analyzed the association between travel time and initial LDCT completion within an integrated, urban safety-net health care system. METHODS: Using Esri's StreetMap Premium, OpenStreetMap, and the r5r package in R, we determined projected private vehicle and public transportation travel times between patient residence and the screening facility for LDCT ordered in March 2017 through December 2022 at Parkland Memorial Hospital in Dallas, Texas. We characterized associations between travel time and LDCT completion in univariable and multivariable analyses. We tested these associations in a simulation of 10,000 permutations of private vehicle and public transportation distribution. RESULTS: A total of 2,287 patients were included in the analysis, of whom 1,553 (68%) completed the initial ordered LDCT. Mean age was 63 years, and 73% were underrepresented minorities. Median travel time from patient residence to the LDCT screening facility was 17 minutes by private vehicle and 67 minutes by public transportation. There was a small difference in travel time to the LDCT screening facility by public transportation for patients who completed LDCT versus those who did not (67 vs 66 min, respectively; P=.04) but no difference in travel time by private vehicle for these patients (17 min for both; P=.67). In multivariable analysis, LDCT completion was not associated with projected travel time to the LDCT facility by private vehicle (odds ratio, 1.01; 95% CI, 0.82-1.25) or public transportation (odds ratio, 1.14; 95% CI, 0.89-1.44). Similar results were noted across travel-type permutations. Black individuals were 29% less likely to complete LDCT screening compared with White individuals. CONCLUSIONS: In an urban population comprising predominantly underrepresented minorities, projected travel time is not associated with initial LDCT completion in an integrated health care system. Other reasons for differences in LDCT completion warrant investigation.

Historical Bias in Mortgage Lending, Redlining, and Implications for the Uncertain Geographic Context Problem: A Study of Structural Housing Discrimination in Dallas and Boston.

According to the uncertain geographic context problem, a lack of temporal information can hinder measures of bias in mortgage lending. This study extends previous methods to: (1) measure the persistence of racial bias in mortgage lending for Black Americans by adding temporal trends and credit scores, and (2) evaluate the continuity of bias in discriminatory areas from 1990 to 2020. These additions create an indicator of persistent structural housing discrimination. We studied the Boston-Cambridge-Newton and Dallas-Fort Worth metropolitan statistical areas to examine distinct historical trajectories and urban development. We estimated the odds of mortgage denial for census tracts. Overall, all tracts in Boston-Cambridge-Newton (N = 1003) and Dallas-Fort Worth (N = 1312) displayed significant change, with greater odds of bias over time in Dallas-Fort Worth and lower odds in Boston-Cambridge-Newton. Historically redlined areas displayed the strongest persistence of bias. Results suggest that temporal data can identify persistence and improve sensitivity in measuring neighborhood bias. Understanding the temporality of residential exposure can increase research rigor and inform policy to reduce the health effects of racial bias.

Immune modulation in chronic myeloid leukaemia patients treated with nilotinib and interferon-alpha.

The addition of interferon to tyrosine kinase inhibitors (TKIs), to improve deep molecular response (DMR) and potentially treatment-free remission (TFR) rates in chronic-phase chronic myeloid leukaemia (CP-CML) patients is under active investigation. However, the immunobiology of this combination is poorly understood. We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon-alpha (IFN-α) within the ALLG CML11 trial (n = 12) or nilotinib alone (n = 17). We demonstrate that nilotinib+IFN transiently reduced absolute counts of natural killer (NK) cells, compared with nilotinib alone. Furthermore, CD16+ -cytolytic and CD57+ CD62L- -mature NK cells were transiently reduced during IFN therapy, without affecting NK-cell function. IFN transiently increased cytotoxic T-lymphocyte (CTL) responses to leukaemia-associated antigens (LAAs) proteinase-3, BMI-1 and PRAME; and had no effect on regulatory T cells, or myeloid-derived suppressor cells. Patients on nilotinib+IFN who achieved MR4.5 by 12 months had a significantly higher proportion of NK cells expressing NKp46, NKp30 and NKG2D compared with patients not achieving this milestone. This difference was not observed in the nilotinib-alone group. The addition of IFN to nilotinib drives an increase in NK-activating receptors, CTLs responding to LAAs and results in transient immune modulation, which may influence earlier DMR, and its effect on long-term outcomes warrants further investigation.

Distance spectacle-wearing habits in older patients in England.

PURPOSE: To report the proportion of older people in England who wear distance spectacles full time, part time and rarely, and to investigate factors that influence how much the distance vision (DV) correction is worn. METHODS: A two-part questionnaire investigating the spectacle-wearing habits of older people was developed and completed by 322 participants (age 72 years ±7.7, range 60-94). A subcohort of 209 DV correction wearers with a mean spherical equivalent (MSE) of <±4.00DS was selected for a logistic regression to investigate which factors influence how much the DV correction is used. RESULTS: In total, 43% of emmetropic, and 55% of pseudophakic, DV spectacle wearers wear their correction full time. Lens type, MSE and the age that participants first wore a DV correction significantly predicted DV correction wearing habit (adjusted R2 = 0.36), with lens type being the strongest predicting factor and progressive users wearing their spectacles 37% more than those using single vision lenses. CONCLUSIONS: Many patients appear to consider convenience more important than being spectacle independent at distance, with lens type the most significant influencing factor of how much those with low/moderate refractive error wear their distance correction. Many emmetropes and pseudophakes choose to wear their progressive or bifocal spectacles full time, and the emmetropia provided by cataract surgery does not provide independence from full-time spectacle wear for many patients. The optometrist has a key role in discussing both choice of spectacle lens correction and the refractive outcome options of cataract surgery with patients.

Impact of a dietitian in general practice: paediatric food allergy.

BACKGROUND: Food allergy in infants and young children places a significant burden on primary care. This study evaluated a dietetic-led paediatric food allergy service, which attempts to provide more rapid access to the dietitian and reduce the need for general practitioner (GP) and secondary care appointments. METHODS: Two community dietetic services for children referred with food allergy were compared. The first was dietetic-led care where dietitians train community children's nurses to recognise potential cases of food allergy, undertake basic diagnostic assessment and subsequently refer to the dietitian. The other was a more traditional dietetic community service where patients were referred predominantly by the GP or secondary care. RESULTS: In dietetic-led care 86 patients were seen, compared to 96 in dietetic community care. Dietetic-led care received fewer referrals from the GP, 36% versus 67% (p < 0.001); GP appointments for allergy-related conditions prior to dietetic referral were lower, 3 versus 6 visits (p = 0.001); and input from secondary care was also lower, 8 versus 25 patients (p = 0.002) compared with dietetic community care. Children referred to dietetic-led care were younger, 78% <6 months versus 40% (p < 0.001) in dietetic community care. CONCLUSIONS: Dietetic-led care describes a model that has the potential to reduce GP and secondary care appointments, identify patients more quickly and reduce the time to receive dietetic input, thereby resolving symptoms more quickly and reducing prescribed medications. This model demonstrates the importance of integrated care and multidisciplinary working, offering a solution to reducing GP workload while maintaining or improving patient care.

The Association of a Geographically Wide Social Media Network on Depression: County-Level Ecological Analysis.

BACKGROUND: Social connectedness decreases human mortality, improves cancer survival, cardiovascular health, and body mass, results in better-controlled glucose levels, and strengthens mental health. However, few public health studies have leveraged large social media data sets to classify user network structure and geographic reach rather than the sole use of social media platforms. OBJECTIVE: The objective of this study was to determine the association between population-level digital social connectedness and reach and depression in the population across geographies of the United States. METHODS: Our study used an ecological assessment of aggregated, cross-sectional population measures of social connectedness, and self-reported depression across all counties in the United States. This study included all 3142 counties in the contiguous United States. We used measures obtained between 2018 and 2020 for adult residents in the study area. The study's main exposure of interest is the Social Connectedness Index (SCI), a pair-wise composite index describing the "strength of connectedness between 2 geographic areas as represented by Facebook friendship ties." This measure describes the density and geographical reach of average county residents' social network using Facebook friendships and can differentiate between local and long-distance Facebook connections. The study's outcome of interest is self-reported depressive disorder as published by the Centers for Disease Control and Prevention. RESULTS: On average, 21% (21/100) of all adult residents in the United States reported a depressive disorder. Depression frequency was the lowest for counties in the Northeast (18.6%) and was highest for southern counties (22.4%). Social networks in northeastern counties involved moderately local connections (SCI 5-10 the 20th percentile for n=70, 36% of counties), whereas social networks in Midwest, southern, and western counties contained mostly local connections (SCI 1-2 the 20th percentile for n=598, 56.7%, n=401, 28.2%, and n=159, 38.4%, respectively). As the quantity and distance that social connections span (ie, SCI) increased, the prevalence of depressive disorders decreased by 0.3% (SE 0.1%) per rank. CONCLUSIONS: Social connectedness and depression showed, after adjusting for confounding factors such as income, education, cohabitation, natural resources, employment categories, accessibility, and urbanicity, that a greater social connectedness score is associated with a decreased prevalence of depression.

Correction: The Association of a Geographically Wide Social Media Network on Depression: County-Level Ecological Analysis.

[This corrects the article DOI: 10.2196/43623.].

Real-world evaluation of osteoporotic fractures using the Japan Medical Data Vision database.

In Japanese patients who experienced an osteoporotic fracture, 10.8% and 18.6% had a subsequent fracture within 1 and 2 years of follow-up, respectively. Although the burden of hip and vertebral fractures has been reported widely, we found that patients with non-hip non-vertebral (NHNV) fractures had a 26% higher risk of subsequent fracture than patients with hip fractures; therefore, NHNV fractures should also be considered an important risk factor for subsequent fracture. INTRODUCTION: To investigate imminent risk and odds of subsequent osteoporotic fractures and associated risk factors in patients who experienced an initial osteoporotic fracture. METHODS: Patients aged ≥ 50 years with ≥ 1 osteoporotic fracture were analyzed from Japan's Medical Data Vision (MDV) database of claims from acute-care hospitals (January 2012-January 2017). Multivariable models were constructed to explore the impact of key comorbidities and medications on the subsequent fracture risk: Cox proportional hazards model for time to subsequent fracture and logistic regression models for odds of subsequent fracture within 1 and 2 years from index fracture. RESULTS: In total, 32,926 patients were eligible with a median follow-up duration of 12.3 months. The percentage of patients experiencing subsequent fractures was 14.1% across the study duration, and 10.8% and 18.6% in patients with 1 and 2 years of follow-up, respectively. In the Cox proportional hazards model, patients with vertebral or NHNV index fractures had a higher subsequent fracture risk than patients with a hip index fracture (adjusted hazard ratio [aHR] 1.11 and 1.26, respectively); subsequent fracture risk was lower in males than females (aHR 0.89). Patients with baseline claims for tranquilizers and glucocorticoids had a higher subsequent fracture risk than those without (aHR 1.14 and 1.08, respectively). Additionally, baseline claims for anti-Parkinson's medications, alcoholism, and stage 4/5 chronic kidney disease were significantly associated with higher odds of subsequent fracture in the logistic regression models. CONCLUSION: Several clinical and demographic factors were associated with a higher risk and odds of subsequent fracture. This may help to identify patients who should be prioritized for osteoporosis treatment.

District-Level Universal Masking Policies and COVID-19 Incidence During the First 8 Weeks of School in Texas.

Texas discontinued state-sponsored business restrictions and mask mandates on March 10, 2021, and mandated that no government officials, including public school officials, may implement mask requirements even in areas where COVID-19 hospitalizations comprised more than 15% of hospitalizations. Nonetheless, some public school districts began the 2021-2022 school year with mask mandates in place. We used quasi-experimental methods to analyze the impact of school mask mandates, which appear to have resulted in approximately 40 fewer student cases per week in the first eight weeks of school. (Am J Public Health. 2022;112(6):871-875. https://doi.org/10.2105/AJPH.2022.306769).

Residence in a Latinx enclave and end-induction minimal residual disease positivity among children with acute lymphoblastic leukemia.

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase 1.63, CI 1.12-2.46). There was also a significant trend toward increased odds of MRD positivity among children living in areas with the highest enclave index scores. MRD positivity at end of induction is associated with higher incidence of relapse and lower overall survival among children with ALL; future studies are needed to elucidate the exact causes of these findings and to improve ALL outcomes among children residing within Latinx enclaves.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2047850.

Disparities in Kidney Stone Disease: A Scoping Review.

PURPOSE: We reviewed the available evidence regarding health disparities in kidney stone disease to identify knowledge gaps in this area. MATERIALS AND METHODS: A literature search was conducted using PubMed®, Embase® and Scopus® limited to articles published in English from 1971 to 2020. Articles were selected based on their relevance to disparities in kidney stone disease among adults in the United States. RESULTS: Several large epidemiological studies suggest disproportionate increases in incidence and prevalence of kidney stone disease among women as well as Black and Hispanic individuals in the United States, whereas other studies of comparable size do not report racial and ethnic demographics. Numerous articles describe disparities in imaging utilization, metabolic workup completion, analgesia, surgical intervention, stone burden at presentation, surgical complications, followup, and quality of life based on race, ethnicity, socioeconomic status and place of residence. Differences in urinary parameters based on race, ethnicity and socioeconomic status may be explained by both dietary and physiological factors. All articles assessed had substantial risk of selection bias and confounding. CONCLUSIONS: Health disparities are present in many aspects of kidney stone disease. Further research should focus not only on characterization of these disparities but also on interventions to reduce or eliminate them.

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review.

BACKGROUND: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. METHODS: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. RESULTS: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). CONCLUSIONS: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.

What are patients' beliefs about, and experiences of, adaptation to glasses and how does this affect their wearing habits?

PURPOSE: It is well known that some patients experience difficulties adapting to new glasses. However, little is known about what patients themselves understand of the adaptation process, and how this influences their attitudes and the decisions they make when adapting to a new pair of glasses. Nor is it understood whether these factors affect their wearing habits. METHODS: We conducted four focus groups. Participants were 22 glasses wearers (mean ± SD age 43 ± 14 years, range 21-71 years) who reported they: (1) wore spectacle correction for distance vision (single vision, bifocal or progressive lenses); (2) had struggled to get used to a new pair of glasses and (3) sometimes chose not to wear their distance correction. Focus groups were audio recorded, transcribed verbatim and analysed thematically. RESULTS: We identified three themes. Trust is about how participants' trust in their optometrist and themselves influences the likelihood of them adapting successfully to new glasses. Conflict describes how the advice patients have received about adapting to glasses can conflict with what they have experienced and how this conflict influences their expectations. Part of Me explores how participants' experiences and feelings about their glasses are important to adaptation and this includes physical, visual, emotional and behavioural aspects. CONCLUSIONS: The traditional optometric perspective of adaptation to glasses is much narrower than that held by patients, and significantly underestimates the physical, behavioural and emotional adaptation that patients must go through in order to feel fully comfortable wearing their glasses. Patients should receive significantly more information about adaptation, including symptoms that may be experienced and why these happen, practical tips to aid adaptation, and when and how to raise concerns. Patients should also receive information about the day-to-day effects of blur adaptation to avoid them not wearing their glasses, including for vision-critical tasks such as driving.

Capacity Building Together: Shifting Roles for Research and Implementation in Health Resilience Among American Indians in Arizona.

Community engagement has become a leading framework for supporting health equity. The process of engagement includes groups working together to continually identify and erode existing inequalities to promote a justice-oriented approach to health and wellness for all. Missing from the literature is a fine-grained study of processes that occur between and among project partners building the foundation for ongoing trust and reciprocity. Our project, Health Resilience among American Indians in Arizona, brought new and seasoned researchers together to collect and analyze data on healthcare provider knowledge and American Indian resilience. Four years after the conclusion of the project, central members of the team developed a postproject self-assessment to investigate lasting impacts of project participation using what we call an "Iterative Poly-knowledge Evaluation Cycle approach." Results highlight the value of flexibility of roles and organic change within projects, the importance of a focus on strengths rather than deficits, and the identification of lasting change on project team members at all levels to build and bolster multisectoral scaffolding for partnerships for health. We present this case study to contribute to an understanding of impacts of community-engaged, Indigenous research projects on people who work together toward challenging existing systems of inequality for better community health.

Nativity, ethnic enclave residence, and breast cancer survival among Latinas: Variations between California and Texas.

BACKGROUND: Among Latinas with breast cancer, residence in an ethnic enclave may be associated with survival. However, findings from prior studies are inconsistent. METHODS: The authors conducted parallel analyses of California and Texas cancer registry data for adult (aged ≥18 years) Latinas who were diagnosed with invasive breast cancer from 1996 to 2005, with follow-up through 2014. Existing indices applied to tract-level 2000 US Census data were used to measure Latinx enclaves and neighborhood socioeconomic status (nSES). Multivariable Cox proportional hazard models were fit for all-cause and breast cancer-specific survival adjusted for year of diagnosis, patient age, nativity (with multiple imputation), tumor stage, histology, grade, size, and clustering by census tract. RESULTS: Among 38,858 Latinas, the majority (61.3% in California and 70.5% in Texas) lived in enclaves. In fully adjusted models for both states, foreign-born women were found to be more likely to die of breast cancer and all causes when compared with US-born women. Living in enclaves and in neighborhoods with higher SES were found to be independently associated with improved survival from both causes. When combined into a 4-level variable, those in low nSES nonenclaves had worse survival for both causes compared with those living in low nSES enclaves and, in the all-cause but not breast cancer-specific models, those in high nSES neighborhoods, regardless of enclave status, had improved survival from all causes. CONCLUSIONS: Applying the same methods across 2 states eliminated previously published inconsistent associations between enclave residence and breast cancer survival. Future studies should identify specific protective effects of enclave residence to inform interventions.

Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells.

There is currently no biomarker that reliably predicts treatment-free remission (TFR) in chronic myeloid leukaemia (CML). We characterised effector and suppressor immune responses at the time of tyrosine kinase inhibitor (TKI) cessation in patients from the CML8 and CML10 clinical studies. Natural killer (NK) cells with increased expression of activating NK receptors were higher in patients who achieved TFR. There was no difference in the proportion of CD4+ or CD8+ T cells. Furthermore, we found that FoxP3+ regulatory T cells (T reg) and monocytic myeloid-derived suppressor cells (Mo-MDSCs) were concomitantly decreased in TFR patients, suggesting that the effector and suppressor arms of the immune system work in concert to mediate TFR. A discovery cohort (CML10) was used to generate a predictive model, using logistic regression. Patients classified into the high-risk group were more likely to relapse when compared with the low-risk group (HR 7·4, 95% CI 2·9-19·1). The model was successfully validated on the independent CML8 cohort (HR 8·3, 95% CI 2·2-31·3). Effective prediction of TFR success may be obtained with an effector-suppressor score, calculated using absolute NK cell, T reg, and Mo-MDSC counts, at TKI cessation, reflecting the contribution of both immune suppressors and effectors in the immunobiology underlying successful TFR.

Do mobile units contribute to spatial accessibility to mammography for uninsured women?

Limited spatial accessibility to mammography, and socioeconomic barriers (e.g., being uninsured), may contribute to rural disparities in breast cancer screening. Although mobile mammography may contribute to population-level access, few studies have investigated this relationship. We measured mammography access for uninsured women using the variable two-step floating catchment area (V2SFCA) method, which estimates access at the local level using estimated potential supply and demand. Specifically, we measured supply with mammography machine certifications in 2014 from FDA and brick-and-mortar and mobile facility data from the community-based Breast Screening and Patient Navigation (BSPAN) program. We measured potential demand using Census tract-level estimates of female residents aged 45-74 from 5-year 2012-2016 American Community Survey data. Using the sign test, we compared mammography access estimates based on 3 facility groupings: FDA-certified, program brick-and-mortar only, and brick-and-mortar plus mobile. Using all mammography facilities, accessibility was high in urban Dallas-Ft. Worth, low for the ring of adjacent counties, and high for rural counties outlying this ring. Brick-and-mortar-based estimates were lower for the outlying ring, and mobile-unit contribution to access was observed more in urban tracts. Weak mobile-unit contribution across the study area may indicate suboptimal dispatch of mobile units to locations. Geospatial methods could identify the optimal locations for mobile units, given existing brick-and-mortar facilities, to increase access for underserved areas.

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors.

Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n = 8), MMR (BCR-ABL1 ≤0.1%, n = 20), molecular response4.5 (MR4.5, BCR-ABL1 ≤0.0032%, n = 16), and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n = 13). Aberrant immune-inhibitory responses (myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and programmed death-1 (PD-1) inhibitory molecule expression on CD4+/CD8+ T cells were increased in CML patients at diagnosis. Consequent quantitative and functional defects of innate effector natural killer (NK) cells and cytotoxic T-lymphocyte responses to leukemia-associated antigens WT1, BMI-1, PR3, and PRAME were observed at diagnosis. Treg and PD-1+CD4+/CD8+ T cells persisted in pre-MMR CML patients on TKI. Patients in MMR and MR4.5 had a more mature, cytolytic CD57+CD62L- NK cell phenotype, consistent with restoration of NK cell activating and inhibitory receptor repertoire to normal healthy donor levels. Immune responses were retained in TFR patients off-therapy, suggesting the restored immune control observed in MMR and MR4.5 is not an entirely TKI-mediated effect. Maximal restoration of immune responses occurred only in MR4.5, as demonstrated by increased NK cell and effector T-cell cytolytic function, reduced T-cell PD-1 expression and reduced numbers of monocytic MDSCs.