Geographic, Patient, and VA Medical Center Variation in the Receipt and Mode of Primary Care in a National Sample of Veterans with Diabetes during 2020.

While telemedicine infrastructure was in place within the Veterans Health Administration (VHA) healthcare system before the onset of the COVID-19 pandemic, geographically varying ordinances/closures disrupted vital care for chronic disease patients such as those with type 2 diabetes. We created a national cohort of 1,647,158 non-Hispanic White, non-Hispanic Black, and Hispanic veterans with diabetes including patients with at least one primary care visit and HbA1c lab result between 3.5% and 20% in the fiscal year (FY) 2018 or 2019. For each VAMC, the proportion of telehealth visits in FY 2019 was calculated. Two logistic Bayesian spatial models were employed for in-person primary care or telehealth primary care in the fourth quarter of the FY 2020, with spatial random effects incorporated at the VA medical center (MC) catchment area level. Finally, we computed and mapped the posterior probability of receipt of primary care for an "average" patient within each catchment area. Non-Hispanic Black veterans and Hispanic veterans were less likely to receive in-person primary care but more likely to receive tele-primary care than non-Hispanic white veterans during the study period. Veterans living in the most socially vulnerable areas were more likely to receive telehealth primary care in the fourth quarter of FY 2020 compared to the least socially vulnerable group but were less likely to receive in-person care. In summary, racial minorities and those in the most socially vulnerable areas were less likely to receive in-person primary care but more likely to receive telehealth primary care, potentially indicating a disparity in the impact of the pandemic across these groups.

Allochthonous marsh subsidies enhances food web productivity in an estuary and its surrounding ecosystem mosaic.

Terrestrial organic matter is believed to play an important role in promoting resilient estuarine food webs, but the inherent interconnectivity of estuarine systems often obscures the origins and importance of these terrestrial inputs. To determine the relative contributions of terrestrial (allochthonous) and aquatic (autochthonous) organic matter to the estuarine food web, we analyzed carbon, nitrogen, and sulfur stable isotopes from multiple trophic levels, environmental strata, and habitats throughout the estuarine habitat mosaic. We used a Bayesian stable isotope mixing model (SIMM) to parse out relationships among primary producers, invertebrates, and a pelagic and demersal fish species (juvenile Chinook salmon and sculpin, respectively). The study was carried out in the Nisqually River Delta (NRD), Washington, USA, a recently-restored, macrotidal estuary with a diverse habitat mosaic. Plant groupings of macroalgae, eelgrass, and tidal marsh plants served as the primary base components of the NRD food web. About 90% of demersal sculpin diets were comprised of benthic and pelagic crustaceans that were fed by autochthonous organic matter contributions from aquatic vegetation. Juvenile salmon, on the other hand, derived their energy from a mix of terrestrial, pelagic, and benthic prey, including insects, dipterans, and crustaceans. Consequently, allochthonous terrestrial contributions of organic matter were much greater for salmon, ranging between 26 and 43%. These findings demonstrate how connectivity among estuarine habitat types and environmental strata facilitates organic matter subsidies. This suggests that management actions that improve or restore lateral habitat connectivity as well as terrestrial-aquatic linkages may enhance allochthonous subsidies, promoting increased prey resources and ecosystem benefits in estuaries.

Geographic variation in diabetic retinopathy screening within the Veterans Health Administration.

AIMS: Diabetic retinopathy (DR) remains the leading cause of vision impairment among working-age adults in the United States. The Veterans Health Administration (VA) supplemented its DR screening efforts with teleretinal imaging in 2006. Despite its scale and longevity, no national data on the VA's screening program exists since 1998. Our objective was to determine the influence of geography on diabetic retinopathy screening adherence. METHODS: Setting: VA national electronic medical records. STUDY POPULATION: A national cohort of 940,654 veterans with diabetes (defined as two or more diabetes ICD-9 codes (250.xx)) without a history of DR. EXPOSURES: 125 VA Medical Center catchment areas, demographics, comorbidity burden, mean HbA1c levels, medication use and adherence, as well as utilization and access metrics. MAIN OUTCOME MEASURE: Screening for diabetic retinopathy within the VA medical system within a 2-year period. RESULTS: Within a 2-year time frame 74 % of veterans without a history of DR received retinal screenings within the VA system. After adjustment for age, gender, race-ethnic group, service-connected disability, marital status, and the van Walraven Elixhauser comorbidity score, the prevalence of DR screening varied by VA catchment area with values ranging from 27 % to 86 %. These differences persisted after further adjusting for mean HbA1c level, medication use and adherence as well as utilization and access metrics. CONCLUSIONS: The wide variability in DR screening across 125 VA catchment areas indicates the presence of unmeasured determinants of DR screening. These results are relevant to clinical decision making in DR screening resource allocation.

Development and psychometric evaluation of the Aversion to Bowel Cancer Screening Scale.

OBJECTIVE: Avoidance of colorectal cancer (CRC) screening is well documented with emotional barriers deterring screening intention and uptake. However, the assessment of such aversion is limited by the available instruments focusing on siloed emotions or screening procedures, limiting relevance to the complete process of decision-making in the CRC context. METHODS: To address this gap, psychometric properties of the newly developed Aversion to Bowel Cancer Screening Scale (ABCSS) were assessed using data from 640 CRC screening eligible asymptomatic community members. Item review and piloting reduced 179 items to the initial 29-item scale. Using a holdout sample technique, exploratory and confirmatory factor analysis, reliability and validity checks were conducted. RESULTS: A three-factor model (Fecal Occult Blood Test [FOBT] Aversion, Colonoscopy Aversion and Health Conscientiousness) with 21 items was identified. Analyses of the 21-item ABCSS indicated excellent reliabilities for the scale and subscales (α = .91 to .95). Correlations with relevant existing measures, intention and behaviour indicated good construct validity. CONCLUSION: The ABCSS is a valid measure of aversion to CRC screening for asymptomatic community members facing the decision to undertake CRC screening. This instrument may provide a more comprehensive understanding of the decision-making process for CRC screening.

School-related sedentary behaviours and indicators of health and well-being among children and youth: a systematic review.

BACKGROUND: The purpose of this systematic review was to examine the associations between school-related sedentary behaviours and indicators of health and well-being in children and youth (~ 5-18 years) attending school. METHODS: This review was conducted to inform the development of School-Related Sedentary Behaviour Recommendations. Peer-reviewed, published, or in-press articles in English were included. Reviews, meta-analyses, and case studies were excluded; all other study designs were eligible. Further, articles had to meet the a priori study criteria for population, intervention, comparator (PROSPERO ID: CRD42021227600). Embase, MEDLINE® ALL, and PsycINFO were searched. Risk of bias was assessed for individual experimental studies using the Cochrane risk of bias assessment tool, and in observational studies based on the GRADE framework and in line with previous systematic reviews examining sedentary behaviours in children. Overall quality of evidence was assessed using the GRADE framework for each outcome category and study design. Results were synthesized narratively, grouped by study design and outcome category. Further, several high-level summaries were conducted to help interpret results. RESULTS: Evidence was synthesized from 116 reports, including 1,385,038 participants and 1173 extracted associations. More school-related sedentary behaviour was favourably associated with nearly one-third of extracted associations for cognitive (33%) and social-emotional (32%) indicators (e.g., less anxiety), but unfavourably associated with other movement behaviours (e.g., less physical activity) (35%). Active lessons were favourable (72%), compared to more school-related sedentary behaviours, when examining associations for all health and well-being indicators. More homework was favourable across all health and well-being indicators in 4% of extracted associations for primary school children, and 25% of extracted associations for secondary school children. However, ≥2 h/day of homework appeared to be unfavourable for health and well-being. Limitations for synthesized studies included generally low quality of evidence and a lack of studies in South American, African, or low-middle income countries. CONCLUSIONS: Findings can help inform policy makers, schools, and teachers, regarding the amount of homework assigned and the introduction of active lessons into the classroom to enhance health and well-being of children. More research is needed examining school-related sedentary behaviours and indicators of health and well-being in low- and middle-income countries.

International school-related sedentary behaviour recommendations for children and youth.

BACKGROUND: Existing sedentary behaviour guidelines for children and youth target overall sedentary behaviour and recreational screen time, without any specific recommendations regarding school-related sedentary behaviours (i.e., sedentary behaviours performed during the school day, or within the influence of school). The purpose of this paper is to describe the development of international evidence-based recommendations for school-related sedentary behaviours for children and youth, led by the Sedentary Behaviour Research Network (SBRN). METHODS: A panel of international experts was convened by SBRN in November 2020 to guide the development of these recommendations for children and youth aged ~ 5-18 years. The recommendations were informed by 1) age-relevant existing sedentary behaviour guidelines, 2) published research on the relationship between overall sedentary behaviour and health, 3) a de novo systematic review on the relationship between school-related sedentary behaviours and health and/or academic outcomes, and 4) a de novo environmental scan of the grey literature to identify existing recommendations for school-related sedentary behaviours. Draft recommendations were presented to the Expert Panel in June 2021. Following thorough discussion and modifications, updated recommendations were distributed for stakeholder feedback from July 9-26. Feedback was received from 148 stakeholders across 23 countries, leading to additional updates to the recommendations. Following further rounds of discussion and updates with the Expert Panel in August and September 2021, consensus was achieved on the final recommendations. RESULTS: A healthy day includes breaking up extended periods of sedentary behaviour and incorporating different types of movement into homework whenever possible, while limiting sedentary homework. School-related screen time should be meaningful, mentally or physically active, and serve a specific pedagogical purpose that enhances learning. Replacing sedentary learning activities with movement-based learning activities, and replacing screen-based learning activities with non-screen-based learning activities, can further support students' health and wellbeing. DISCUSSION: This paper presents the first evidence-based recommendations for school-related sedentary behaviours for children and youth. These recommendations will support the work of parents, caregivers, educators, school system administrators, policy makers, researchers and healthcare providers interested in promoting student health and academic success.

Implementation of Magnetic Resonance Safety Program for Radiation Oncology.

During the last decade, radiation oncology departments have integrated magnetic resonance imaging (MRI) equipment, procedures, and expertise into their practices. MRI safety is an important consideration because a large percentage of patients receiving radiation therapy have histories of multiple surgeries and implanted devices. However, MRI safety guidelines and workflows were traditionally designed for radiology departments. This report presents an MR safety program designed for a radiation oncology department to address its specific needs.

Propensity score matching for multilevel spatial data: accounting for geographic confounding in health disparity studies.

BACKGROUND: Diabetes is a public health burden that disproportionately affects military veterans and racial minorities. Studies of racial disparities are inherently observational, and thus may require the use of methods such as Propensity Score Analysis (PSA). While traditional PSA accounts for patient-level factors, this may not be sufficient when patients are clustered at the geographic level and thus important confounders, whether observed or unobserved, vary by geographic location. METHODS: We employ a spatial propensity score matching method to account for "geographic confounding", which occurs when the confounding factors, whether observed or unobserved, vary by geographic region. We augment the propensity score and outcome models with spatial random effects, which are assigned scaled Besag-York-Mollié priors to address spatial clustering and improve inferences by borrowing information across neighboring geographic regions. We apply this approach to a study exploring racial disparities in diabetes specialty care between non-Hispanic black and non-Hispanic white veterans. We construct multiple global estimates of the risk difference in diabetes care: a crude unadjusted estimate, an estimate based solely on patient-level matching, and an estimate that incorporates both patient and spatial information. RESULTS: In simulation we show that in the presence of an unmeasured geographic confounder, ignoring spatial heterogeneity results in increased relative bias and mean squared error, whereas incorporating spatial random effects improves inferences. In our study of racial disparities in diabetes specialty care, the crude unadjusted estimate suggests that specialty care is more prevalent among non-Hispanic blacks, while patient-level matching indicates that it is less prevalent. Hierarchical spatial matching supports the latter conclusion, with a further increase in the magnitude of the disparity. CONCLUSIONS: These results highlight the importance of accounting for spatial heterogeneity in propensity score analysis, and suggest the need for clinical care and management strategies that are culturally sensitive and racially inclusive.

Maturational timing, physical self-perceptions and physical activity in UK adolescent females: investigation of a mediated effects model.

BACKGROUND: Advanced (early) biological maturation may be a risk factor for inactivity among adolescent girls. AIM: To test the mediational effects of body attractiveness and physical self-worth on the relationship between biological maturity and accelerometer assessed moderate-to-vigorous physical activity (MVPA) in a large multi-ethnic sample of girls from the Midlands area in the UK (11-14 years). SUBJECTS AND METHODS: Biological maturity (predicting age at peak height velocity (APHV)); self-perceptions of body attractiveness, physical self-worth, and minutes spent in MVPA were assessed in 1062 females aged 11-14 years. RESULTS: Structural equation modelling using maximum likelihood estimation and boot- strapping procedures supported the hypothesised model. Later maturation predicted higher perceptions of body attractiveness (ß = 0.25, p < .001) which, in turn, predicted higher perceptions of physical self-worth (ß = 0.91, p < .001) and, significantly higher MVPA (ß = 0.22, p < .001). Examination of the bootstrap-generated bias-corrected confidence intervals suggested that perceptions of body attractiveness and physical self-worth partially mediated a positive association between predicted APHV and MVPA (ß = 0.05, p < .001). CONCLUSIONS: Greater biological maturity (i.e. early maturity) in adolescent girls is associated with less involvement in MVPA and appears to be partly explained by lower perceptions of body attractiveness and physical self-worth. Physical activity interventions should consider girls' perceptions of their pubertal related physiological changes during adolescence, particularly among early maturing girls.

Geographic and Racial/Ethnic Variation in Glycemic Control and Treatment in a National Sample of Veterans With Diabetes.

OBJECTIVE: Geographic and racial/ethnic disparities related to diabetes control and treatment have not previously been examined at the national level. RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted in a national cohort of 1,140,634 veterans with diabetes, defined as two or more diabetes ICD-9 codes (250.xx) across inpatient and outpatient records. Main exposures of interest included 125 Veterans Administration Medical Center (VAMC) catchment areas as well as racial/ethnic group. The main outcome measure was HbA1c level dichotomized at ≥8.0% (≥64 mmol/mol). RESULTS: After adjustment for age, sex, racial/ethnic group, service-connected disability, marital status, and the van Walraven Elixhauser comorbidity score, the prevalence of uncontrolled diabetes varied by VAMC catchment area, with values ranging from 19.1% to 29.2%. Moreover, these differences largely persisted after further adjusting for medication use and adherence as well as utilization and access metrics. Racial/ethnic differences in diabetes control were also noted. In our final models, compared with non-Hispanic Whites, non-Hispanic Blacks (odds ratio 1.11 [95% credible interval 1.09-1.14]) and Hispanics (1.36 [1.09-1.14]) had a higher odds of uncontrolled HBA1c level. CONCLUSIONS: In a national cohort of veterans with diabetes, we found geographic as well as racial/ethnic differences in diabetes control rates that were not explained by adjustment for demographics, comorbidity burden, use or type of diabetes medication, health care utilization, access metrics, or medication adherence. Moreover, disparities in suboptimal control appeared consistent across most, but not all, VAMC catchment areas, with non-Hispanic Black and Hispanic veterans having a higher odds of suboptimal diabetes control than non-Hispanic White veterans.

Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma.

BACKGROUND: Among patients with cervical cancer, little is known about the significance of persistent human papillomavirus (HPV) expression after chemoradiation (CRT). This study evaluated associations between early posttreatment HPV clearance and patient outcomes with an added focus on the value of posttherapy positron emission tomography (PET) imaging. METHODS: Included patients underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)-based genital swab after CRT. Posttherapy responses were stratified on the basis of HPV mRNA detection into an early clearance (EC) group (no mRNA) and a persistent expression (PE) group (detectable mRNA) on the basis of an evaluation at a median of 6 weeks after therapy. The Kaplan-Meier method was used to compare outcomes, and multivariable analysis was used to identify predictors of outcomes. RESULTS: Seventy-two of the 97 eligible patients (74.2%) had EC. The mean follow-up time was 25 months (range, 4-56 months), and 2-year pelvic control (76.9% vs 50.2%; P = .01) and overall survival (OS; 80.9% vs 52.2%; P < .01) were superior among EC patients. In the multivariable analysis, EC predicted for improved survival (hazard ratio [HR] for mortality, 0.46; 95% confidence interval [CI], 0.21-0.96; P = .047), as did a complete response (CR) on posttherapy PET (HR for less than a CR on PET, 6.17; 95% CI, 2.58-14.72; P < .01). In a subset analysis of patients with a posttherapy PET CR, HPV clearance retained prognostic significance (2-year OS, 95.6% with EC vs 66.7% with PE; P = .04), whereas PE patients without a PET CR had the worst survival (35.9%; P < .01 for trend). CONCLUSIONS: Early posttherapy clearance of HPV is associated with improved survival in cervical cancer. Evaluating HPV expression at this 6-week time point provides prognostic information beyond posttherapy PET imaging and may aid in risk stratification and decisions for treatment escalation.

Analysis of racial differences in hospital stays in the presence of geographic confounding.

Using recent methods for spatial propensity score modeling, we examine differences in hospital stays between non-Hispanic black and non-Hispanic white veterans with type 2 diabetes. We augment a traditional patient-level propensity score model with a spatial random effect to create a matched sample based on the estimated propensity score. We then use a spatial negative binomial hurdle model to estimate differences in both hospital admissions and inpatient days. We demonstrate that in the presence of unmeasured geographic confounding, spatial propensity score matching in addition to the spatial negative binomial hurdle outcome model yields improved performance compared to the outcome model alone. In the motivating application, we construct three estimates of racial differences in hospitalizations: the risk difference in admission, the mean difference in number of inpatient days among those hospitalized, and the mean difference in number of inpatient days across all patients (hospitalized and non-hospitalized). Results indicate that non-Hispanic black veterans with type 2 diabetes have a lower risk of hospital admission and a greater number of inpatient days on average. The latter result is especially important considering that we observed much smaller effect sizes in analyses that did not incorporate spatial matching. These results emphasize the need to address geographic confounding in health disparity studies.

A Phase I/II Trial of Cetuximab in Combination with Interleukin-12 Administered to Patients with Unresectable Primary or Recurrent Head and Neck Squamous Cell Carcinoma.

PURPOSE: mAbs including cetuximab can induce antibody-dependent cellular cytotoxicity (ADCC) and cytokine production mediated via innate immune cells with the ability to recognize mAb-coated tumors. Preclinical modeling has shown that costimulation of natural killer (NK) cells via the Fc receptor and the IL12 receptor promotes NK-cell-mediated ADCC and production of cytokines. PATIENTS AND METHODS: This phase I/II trial evaluated the combination of cetuximab with IL12 for the treatment of EGFR-expressing head and neck cancer. Treatment consisted of cetuximab 500 mg/m2 i.v. every 2 weeks with either 0.2 mcg/kg or 0.3 mcg/kg IL12 s.c. on days 2 and 5 of the 2-week cycle, beginning with cycle 2. Correlative studies from blood draws obtained prior to treatment and during therapy included measurement of ADCC, serum cytokine, and chemokine analysis, determination of NK cell FcγRIIIa polymorphisms, and an analysis of myeloid-derived suppressor cell (MDSC) frequency in peripheral blood. RESULTS: The combination of cetuximab and IL12 was well tolerated. No clinical responses were observed, however, 48% of patients exhibited prolonged progression-free survival (PFS; average of 6.5 months). Compared with patients that did not exhibit clinical benefit, patients with PFS >100 days exhibited increased ADCC as therapy continued compared with baseline, greater production of IFNγ, IP-10, and TNFα at the beginning of cycle 8 compared with baseline values and had a predominance of monocytic MDSCs versus granulocytic MDSCs prior to therapy. CONCLUSIONS: Further investigation of IL12 as an immunomodulatory agent in combination with cetuximab in head and neck squamous cell carcinoma is warranted.

Child and Family Characteristics that Predict Autism Spectrum Disorder Specialty Clinic Appointment Attendance and Alignment with Providers.

We examined factors contributing to initial appointment attendance, alignment between parents' pre-visit and clinicians' diagnostic impressions, and family commitment to follow-ups at an autism spectrum disorder (ASD) specialty clinic. Sample sizes were n = 6558 (initial), n = 1430 (alignment), and n = 1353 (follow-up). Parents completed surveys and clinicians provided their ASD diagnostic impressions. When children were not receiving intervention, families were less likely to keep their initial appointment. Families residing long distances and having older children were less likely to keep their initial and follow-up appointments. African American families were less likely to keep their initial appointment and expressed initial doubts with providers about the diagnosis. Findings suggest that some children are not getting diagnostic clarity or accessing timely services.

Addressing geographic confounding through spatial propensity scores: a study of racial disparities in diabetes.

Motivated by a study exploring differences in glycemic control between non-Hispanic black and non-Hispanic white veterans with type 2 diabetes, we aim to address a type of confounding that arises in spatially referenced observational studies. Specifically, we develop a spatial doubly robust propensity score estimator to reduce bias associated with geographic confounding, which occurs when measured or unmeasured confounding factors vary by geographic location, leading to imbalanced group comparisons. We augment the doubly robust estimator with spatial random effects, which are assigned conditionally autoregressive priors to improve inferences by borrowing information across neighboring geographic regions. Through a series of simulations, we show that ignoring spatial variation results in increased absolute bias and mean squared error, while the spatial doubly robust estimator performs well under various levels of spatial heterogeneity and moderate sample sizes. In the motivating application, we construct three global estimates of the risk difference between race groups: an unadjusted estimate, a doubly robust estimate that adjusts only for patient-level information, and a hierarchical spatial doubly robust estimate. Results indicate a gradual reduction in the risk difference at each stage, with the inclusion of spatial random effects providing a 20% reduction compared to an estimate that ignores spatial heterogeneity. Smoothed maps indicate poor glycemic control across Alabama and southern Georgia, areas comprising the so-called "stroke belt." These results suggest the need for community-specific interventions to target diabetes in geographic areas of greatest need.

Racial differences in spatial patterns for poor glycemic control in the Southeastern United States.

PURPOSE: Evidence consistently shows poor outcomes in racial minorities, but there is limited understanding of differences that are explained by spatial variation. The goal of this analysis was to examine contribution of spatial patterns on disparities in diabetes outcomes in the Southeastern United States. METHODS: Data on 64,022 non-Hispanic black (NHB) and non-Hispanic white (NHW) veterans with diabetes living in Georgia, Alabama, and South Carolina were analyzed for 2014. Hemoglobin A1c (HbA1c) was categorized as controlled (less than 8%) and uncontrolled (greater than or equal to 8%). Logistic regression was used to understand the additional explanatory capability of spatial random effects over covariates such as demographics, service connectedness, and comorbidities. Data aggregated at the county level were used to identify hotspots in distribution of uncontrolled HbA1c and tested using local Moran's I test. RESULTS: Overall percent uncontrolled HbA1c was 36.5% (40.8% in NHB and 33.4% in NHW). In unadjusted analyses, NHB had 37% higher odds of uncontrolled HbA1c (odds ratio [OR]: 1.37, 95% confidence interval, 1.32, 1.41). After adjusting for demographics and comorbidities, the OR decreased to 1.09 but remained significant (95% confidence interval, 1.05, 1.13). The OR further decreased after incorporating spatial effects (OR: 1.07, 95% confidence interval, 1.03, 1.11) but remained statistically significant. Hotspots of high HbA1c were detected, and spatial patterns differed across racial groups. CONCLUSIONS: Differences in spatial patterns in glycemic control exists between NHB and NHW veterans with type 2 diabetes. Incorporating spatial effects helps explain more of the disparity in uncontrolled HbA1c than adjusting only for demographics and comorbidities, but significant differences in uncontrolled HbA1c remained.

State Variations in Infant Feeding Regulations for Child Care.

OBJECTIVES: Early care and education (ECE) settings have become primary targets for policy change in recent years. In our 2008 study, we assessed state and regional variation in infant feeding regulations for ECE and compared them to national standards. We conducted the same regulatory review to assess change over time. Because all but 2 states have updated their regulations, we hypothesized that states would have made substantial improvements in the number of regulations supporting infant feeding in ECE. METHODS: For this cross-sectional study, we reviewed infant feeding regulations for all US states for child care centers (centers) and family child care homes (homes). We compared regulations with 10 national standards and assessed the number of new regulations consistent with these standards since our previous review. RESULTS: Comparing results from 2008 and 2016, we observed significant improvements in 7 of the 10 standards for centers and 4 of the 10 standards for homes. Delaware was the only state with regulations meeting 9 of the 10 standards for centers in 2008. In 2016, Delaware and Michigan had regulations meeting 8 of the 10 standards. Previously, Arkansas, the District of Columbia, Minnesota, Mississippi, Ohio, and South Carolina had regulations consistent with 4 of the 10 standards for homes. In 2016, Delaware, Mississippi, and Vermont had regulations meeting 7 of the 10 standards. CONCLUSIONS: Evidence suggests that enacting new regulations may improve child health outcomes. Given that many states recently enacted regulations governing infant feeding, our findings point to the growing interest in this area.

BTKC481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia.

Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can cause relapse, but data regarding the prevalence and natural history of these mutations are limited. Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses. Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospectively on a screening population. Results With a median follow-up time of 3.4 years, the estimated cumulative incidence of progression at 4 years is 19% (95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1), and age less than 65 years were risk factors for progression. Among patients who experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95% CI, 71% to 94%), and these mutations were detected an estimated median of 9.3 months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients examined prospectively, eight patients have experienced relapse, and all of these patients had acquired resistance mutations before relapse. A resistance mutation was detected in an additional eight patients who have not yet met criteria for clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance. We show that mutations in BTK and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.

Effect of Induction Therapy on Graft Survival in Primary Pediatric Heart Transplantation: A Propensity Score Analysis of the UNOS Database.

BACKGROUND: The use of induction therapy in pediatric heart transplantation has increased. The aim of this study was to investigate the effects of induction therapy on graft survival. METHODS: The United Network for Organ Sharing database was queried for isolated pediatric heart transplants from January 1, 1994, to December 31, 2013. Propensity scores for induction treatment were calculated by estimating probability of induction using a logistic regression model. Transplants were then matched between induction treatment groups based on the propensity score, reducing potential biases. Using only propensity score matched transplants, the effect of induction therapy on graft survival was investigated using Cox-proportional hazards. Subgroup analyses were performed based on age, race, recipient cardiac diagnosis, HLA, and recipient panel-reactive antibody (PRA). RESULTS: Of 4565 pediatric primary heart transplants from 1994 to 2013, 3741 had complete data for the propensity score calculation. There were 2792 transplants successfully matched (induction, n = 1396; no induction, n = 1396). There were no significant differences in transplant and pretransplant covariates between induction and no induction groups. In the Cox-proportional hazards model, the use of induction of was not associated with graft loss (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.75-1.01; P = 0.07). In subgroup analyses, induction therapy may be associated with improved survival in patients with PRA greater than 50% (HR, 0.57; 95% CI, 0.34-0.97) and congenital heart disease (HR, 0.78; 95% CI, 0.64-0.96). CONCLUSIONS: Induction therapy is not associated with improved graft survival in primary pediatric heart transplantation. However, in pediatric heart transplant recipients with PRA greater than 50% or congenital heart disease, induction therapy is associated with improved survival.

A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer.

mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC. Treatment consisted of cetuximab 500 mg/m(2) i.v. every two weeks with lenalidomide given orally days 1-21 on a 28-day cycle. Three dose levels of lenalidomide were evaluated (15, 20, 25 mg). Correlative studies included measurement of ADCC, FcγRIIIA polymorphism genotyping, measurement of serum cytokine levels, and flow cytometric analysis of immune cell subtypes. Twenty-two patients were enrolled (19 colorectal cancer, 3 HNSCC). Fatigue was the only dose-limiting toxicity. One partial response was observed and 8 patients had stable disease at least 12 weeks. The recommended phase II dose is cetuximab 500 mg/m(2) with lenalidomide 25 mg daily, days 1-21. Correlative studies demonstrated a dose-dependent increase in natural killer cytotoxic activity with increasing doses of lenalidomide. Cetuximab and lenalidomide were well tolerated. There was a lenalidomide dose-dependent increase in ADCC with higher activity in patients enrolled in cohort 3 than those enrolled in cohorts 1/2. Although response was not a primary endpoint, there was evidence of antitumor activity for the combination therapy. Further investigation of lenalidomide as an immunomodulator in solid tumors is warranted. Mol Cancer Ther; 15(9); 2244-50. ©2016 AACR.