Genome-matched treatments and patient outcomes in the Maine Cancer Genomics Initiative (MCGI).

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52-0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

Complications and Practice Variation in the Use of Peripherally Inserted Central Venous Catheters in People With Cystic Fibrosis: The Prospective Study of Peripherally Inserted Venous Catheters in People With Cystic Fibrosis Study.

BACKGROUND: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion. RESEARCH QUESTION: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF? STUDY DESIGN AND METHODS: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both. Three categories of composite secondary outcomes were identified: difficult line placement, local soft tissue or skin reactions, and catheter malfunction. Data specific to the participant, catheter placement, and catheter management were collected in a centralized database. Risk factors for primary and secondary outcomes were analyzed by multivariate logistic regression. RESULTS: Between June 2018 and July 2021, 157 adults and 103 children older than 6 years with CF had 375 PICCs placed. Patients underwent 4,828 catheter-days of observation. Of the 375 PICCs, 334 (89%) were ≤ 4.5 F, 342 (91%) were single lumen, and 366 (98%) were placed using ultrasound guidance. The primary outcome occurred in 15 PICCs for an event rate of 3.11 per 1,000 catheter-days. No cases of catheter-related bloodstream infection occurred. Other secondary outcomes developed in 147 of 375 catheters (39%). Despite evidence of practice variation, no risk factors for the primary outcome and few risk factors for secondary outcomes were identified. INTERPRETATION: This study affirmed the safety of contemporary approaches to inserting and using PICCs in people with CF. Given the low rate of complications in this study, observations may reflect a widespread shift to selecting smaller-diameter PICCs and using ultrasound to guide their placement.

Urban-Rural and Socioeconomic Differences in Patient Knowledge and Perceptions of Genomic Tumor Testing.

PURPOSE: Social determinants of health, such as rurality, income, and education, may widen health disparities by driving variation in patients' knowledge and perceptions of medical interventions. This effect may be greatest for medical technologies that are hard to understand and less accessible. This study explored whether knowledge and perceptions (expectations and attitudes) of patients with cancer toward large-panel genomic tumor testing (GTT), an emerging cancer technology, vary by patient rurality independent of other socioeconomic characteristics (education and income). METHODS: Patients with cancer enrolled in a large precision oncology initiative completed surveys measuring rurality, sociodemographic characteristics, and knowledge and perceptions of GTT. We used multivariable linear models to examine differences in GTT knowledge, expectations, and attitudes by patient rurality, education, and income level. Models controlled for age, sex and clinical cancer stage and type. RESULTS: Rural patients had significantly lower knowledge of GTT than urban patients using bivariate models (P = .025). However, this association disappeared when adjusting for education and income level: patients with lower educational attainment and lower income had lower knowledge and higher expectations (P ≤ .002), whereas patients with higher income had more positive attitudes (P = .005). Urban patients had higher expectations of GTT compared with patients living in large rural areas (P = .011). Rurality was not associated with attitudes. CONCLUSION: Patients' education and income level are associated with knowledge, expectations, and attitudes toward GTT, whereas rurality is associated with patient expectations. These findings suggest that efforts to promote adoption of GTT should focus on improving knowledge and awareness among individuals with low education and income. These differences may lead to downstream disparities in GTT utilization, which should be explored in future research.

NOHA: A Promising Biomarker for Determining Estrogen Receptor Status Among Patients With Breast Cancer in Resource-Constrained Settings.

PURPOSE: Challenges to breast cancer control in low-and middle-income countries exist because of constrained access to care, including pathology services. Immunohistochemistry (IHC)-based estrogen receptor (ER) analysis is limited-nonexistent because of few and inadequately staffed and equipped pathology laboratories. We have identified Nw-hydroxy-L-Arginine (NOHA) as a blood-based biomarker to distinguish ER status in US patients with breast cancer. Here, we examine NOHA's clinical utility as an ER IHC alternative in Tanzanian patients. MATERIALS AND METHODS: Following informed consent, 70 newly diagnosed, known or suspected patients with breast cancer were enrolled at Kilimanjaro Christian Medical Center; basic, deidentified clinical and sociodemographic data were collected. For each, a needle prick amount of blood was collected on a Noviplex plasma card and stored at -80°C. Plasma cards and unstained tumor pathology slides were shipped regularly to US laboratories for NOHA, histologic and IHC analysis. NOHA and IHC assay operators were blinded to each other's result and patient clinical status. Paired NOHA and IHC results were compared. RESULTS: Slides from 43 participants were available for pathological analysis in the United States. Of those with confirmed malignancy (n = 39), 44%, 51%, 5% were ER-positive, ER-negative, and ER inconclusive, respectively. NOHA levels were available among 33 of 43 of those with pathological data and showed distinct threshold levels correlating 100% to tumor ER IHC and disease categorization where a level below 4 nM, from 4 to 8 nM, and above 8 nM signified ER-negative, ER-positive, and no cancer, respectively. CONCLUSION: The results are consistent with findings from US patients and suggest NOHA's clinical utility as an accessible IHC replacement in determining ER status among low-and middle-income country patients with breast cancer, promising to extend access to cost-efficient, available hormonal agents and improve outcomes.

Goal Directed Perfusion Is Not Associated with a Decrease in Acute Kidney Injury in Patients Predicted to Be at High Risk for Acute Renal Failure after Cardiac Surgery.

Small increases in serum creatinine postoperatively reflect an acute kidney injury (AKI) that likely occurred during cardiopulmonary bypass (CPB). Maintaining adequate oxygen delivery (DO2) during CPB, known as GDP (goal-directed perfusion), improves outcomes. Whether GDP improves outcomes of patients at high risk for acute renal failure (ARF) is unknown. Forty-seven adult patients undergoing cardiac surgery with CPB utilizing GDP with Cleveland Clinic Acute Renal Failure Score of 3 or greater were compared with a matched cohort of patients operated upon using a flow-directed strategy. CPB flow in the GDP cohort was based on a DO2 goal of 260 mL/min/m2. Serum creatinine values were used to determine whether postoperative AKI occurred according to AKIN (Acute Kidney Injury Network) guidelines. We examined the distribution of all variables using proportions for categorical variables and means (standard deviations) for continuous variables and compared treatment groups using t tests for categorical variables and tests for differences in distributions for continuous and count variables. We used inverse probability of treatment weighting to adjust for treatment selection bias. In adjusted models, GDP was not associated with a decrease in AKI (odds ratio [OR]: .97; confidence interval [CI]: .62, 1.52), but was associated with higher odds of ARF (OR: 3.13; CI: 1.26, 7.79), mortality (OR: 3.35; CI: 1.14, 9.89), intensive care unit readmission (OR: 2.59; CI: 1.31, 5.15), need for intraoperative red blood cell transfusion (OR: 2.02; CI: 1.26, 3.25), and postoperative platelet transfusion (OR: 1.78; CI: 1.05, 3.01) when compared with the historic cohort. In patients who are at high risk for postoperative renal failure, GDP was not associated with a decrease in AKI when compared to the historical cohort managed traditionally by determining CPB flows based on body surface area. Surprisingly, the GDP cohort performed significantly worse than the retrospective control group in terms of ARF, mortality, intensive care unit readmission, and RBC and platelet transfusions.

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial.

BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

Rural disparities in end-of-life care for patients with heart failure: Are they due to geography or socioeconomic disparity?

PURPOSE: The impact of rurality and socioeconomic deprivation on end-of-life (EOL) care for patients with heart failure (HF) is unknown. We analyzed claims to describe the prevalence and predictors of EOL health care utilization for patients dying with HF in a predominantly rural state. METHODS: We used the MaineHealth Data Organization's All-Payer Claims Data to identify 15,168 patients ≥35 who died with HF between 2012 and 2017. The primary outcome was health care utilization during the last 180 days of life (EOL definition for this analysis), including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and hospice utilization. Patient characteristics analyzed included age, gender, comorbidities, area deprivation index (ADI), and rurality. FINDINGS: Among 15,168 patients ≥35 who died with HF, 48% had ≥2 hospitalizations, 72% had ≥2 ED visit, 29% had an ICU stay, 2% initiated dialysis during EOL, and 64% received hospice. Rural patients were more likely to have an ICU admission and have ≥2 hospitalizations. Patients residing in areas with higher ADI were more likely to be hospitalized, admitted to the ICU, and started on dialysis. Both rural patients and those living in higher ADI areas were less likely to receive hospice. After multivariable adjustment, rurality and ADI were independently associated with a decreased likelihood of receiving hospice (OR 0.62 [95% CI: 0.53-0.72] for the most rural patients and OR 0.64 [95% CI: 0.57-0.72] for the highest ADI). CONCLUSION: Both rurality and local area deprivation drive disparities in EOL care for patients dying with heart failure.

Epistemic Beliefs: Relationship to Future Expectancies and Quality of Life in Cancer Patients.

CONTEXT: Expectations about the future (future expectancies) are important determinants of psychological well-being among cancer patients, but the strategies patients use to maintain positive and cope with negative expectancies are incompletely understood. OBJECTIVES: To obtain preliminary evidence on the potential role of one strategy for managing future expectancies: the adoption of "epistemic beliefs" in fundamental limits to medical knowledge. METHODS: A sample of 1307 primarily advanced-stage cancer patients participating in a genomic tumor testing study in community oncology practices completed measures of epistemic beliefs, positive future expectancies, and mental and physical health-related quality of life (HRQOL). Descriptive and linear regression analyses were conducted to assess the relationships between these factors and test two hypotheses: 1) epistemic beliefs affirming fundamental limits to medical knowledge ("fallibilistic epistemic beliefs") are associated with positive future expectancies and mental HRQOL, and 2) positive future expectancies mediate this association. RESULTS: Participants reported relatively high beliefs in limits to medical knowledge (M = 2.94, s.d.=.67) and positive future expectancies (M = 3.01, s.d.=.62) (range 0-4), and relatively low mental and physical HRQOL. Consistent with hypotheses, fallibilistic epistemic beliefs were associated with positive future expectancies (b = 0.11, SE=.03, P< 0.001) and greater mental HRQOL (b = 0.99, SE=.34, P = 0.004); positive expectancies also mediated the association between epistemic beliefs and mental HRQOL (Sobel Z=4.27, P<0.001). CONCLUSIONS: Epistemic beliefs in limits to medical knowledge are associated with positive future expectancies and greater mental HRQOL; positive expectancies mediate the association between epistemic beliefs and HRQOL. More research is needed to confirm these relationships and elucidate their causal mechanisms.

Patients' Expectations of Benefits From Large-Panel Genomic Tumor Testing in Rural Community Oncology Practices.

Large-panel genomic tumor testing (GTT) is an emerging technology that promises to make cancer treatment more precise. Because GTT is novel and complex, patients may have unrealistic expectations and limited knowledge of its benefits. These problems may limit the clinical value of GTT, but their prevalence and associated factors have not been explored. METHODS: Patients with cancer enrolled in a large initiative to disseminate GTT in community oncology practices completed surveys assessing their expectations, knowledge, and attitudes about GTT. The study sample (N = 1,139) consisted of patients with a range of cancer types (22% gynecologic, 14% lung, 10% colon, 10% breast, and 46% other malignancies) and cancer stages (4% stage I, 3% stage II, 15% stage III, and 74% stage IV). Mean age was 64 years (standard deviation = 11); 668 (59%) were women; 71% had no college degree; 57% came from households with less than $50,000 US dollars household income; and 73% lived in a rural area. RESULTS: Generally, patients had high expectations that they would benefit from GTT (M = 2.81 on 0-4 scale) and positive attitudes toward it (M = 2.98 on 0-4 scale). Patients also had relatively poor knowledge about GTT (48% correct answers on an objective test of GTT knowledge). Greater expectations for GTT were associated with lower knowledge (b = -0.46; P < .001), more positive attitudes (b = 0.40; P < .001), and lower education (b = -0.53; P < .001). CONCLUSION: This research suggests patients have high expectations that they will benefit from GTT, which is associated with low knowledge, positive attitudes, and low education. More research is needed to understand the concordance between expectations and actual clinical outcomes.

mPalliative Care Link: Examination of a Mobile Solution to Palliative Care Coordination Among Tanzanian Patients With Cancer.

PURPOSE: Late-stage cancer patient symptom control is a national priority in Tanzania. Mobile health promises to improve the reach of a limited pool of palliative care specialists through interprofessional, community-based care coordination. This work assessed the effectiveness of a smartphone- or Web-based app, mPalliative Care Link (mPCL), to extend specialist access via shared data and communication with local health workers. Central to mPCL is the African Palliative care Outcome Scale (POS), adapted for automated mobile symptom assessment and response. METHODS: Adult patients with incurable cancer were randomly assigned at hospital discharge to mPCL versus phone-contact POS collection. Sociodemographic, clinical, and POS data were obtained at baseline. Twice-weekly POS responses were collected and managed via mPCL or phone contact with clinician study personnel for up to 4 months, on the basis of study arm assignment. Patient end-of-study care satisfaction was assessed via phone survey. RESULTS: Forty-nine patients per arm participated. Comparison of baseline characteristics showed an insignificant trend toward more women (P = .07) and higher discharge morphine use (P = .09) in the mPCL group compared with phone-contact and significant between-group differences in cancer types (P = .003). Proportions of deaths were near equal between groups (mPCL: 27%; phone-contact: 29%). Overall symptom severity was significantly lower in the phone-contact group (P < .0001), and symptom severity decreased over time in both groups (P = .0001); however, between-group change in overall symptoms over time did not vary significantly (P = .34). Care satisfaction was generally high in both groups. CONCLUSION: Higher symptom severity scores in the mPCL arm likely reflect between-group sociodemographic and clinical differences and clinical support of phone-contact arm participants. Similar rates of care satisfaction in both groups suggest that mPCL may support symptom-focused care coordination in a more efficient and scalable manner than phone contact. A broader study of mPCL's cost efficiency and utility in Tanzania is needed.

How Well Does the Surprise Question Predict 1-year Mortality for Patients Admitted with COPD?

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often receive burdensome care at end-of-life (EOL) and infrequently complete advance care planning (ACP). The surprise question (SQ) is a prognostic tool that may facilitate ACP. OBJECTIVE: To assess how well the SQ predicts mortality and prompts ACP for COPD patients. DESIGN: Retrospective cohort study. SUBJECTS: Patients admitted to the hospital for an acute exacerbation of COPD between July 2015 and September 2018. MAIN MEASURES: Emergency department (ED) and inpatient clinicians answered, "Would you be surprised if this patient died in the next 30 days (ED)/one year (inpatient)?" The primary outcome measure was the accuracy of the SQ in predicting 30-day and 1-year mortality. The secondary outcome was the correlation between SQ and ACP (palliative care consultation, documented goals-of-care conversation, change in code status, or completion of ACP document). KEY RESULTS: The 30-day SQ had a high specificity but low sensitivity for predicting 30-day mortality: sensitivity 12%, specificity 95%, PPV 11%, and NPV 96%. The 1-year SQ demonstrated better accuracy for predicting 1-year mortality: sensitivity 47%, specificity 75%, PPV 35%, and NPV 83%. After multivariable adjustment for age, sex, and prior 6-month admissions, 1-year SQ+ responses were associated with greater odds of 1-year mortality (OR 2.38, 95% CI 1.39-4.08) versus SQ-. One-year SQ+ patients were more likely to have a goals-of-care conversation (25% vs. 11%, p < 0.01) and complete an advance directive or POLST (46% vs. 23%, p < 0.01). After multivariable adjustment, SQ+ responses to the 1-year SQ were associated with greater odds of ACP receipt (OR 2.67, 95% CI 1.64-4.36). CONCLUSIONS: The 1-year surprise question may be an effective component of prognostication and advance care planning for COPD patients in the inpatient setting.

Impact of geography and travel distance on outcomes in epithelial ovarian cancer: a national cancer database analysis.

BACKGROUND: As ovarian cancer treatment shifts to provide more complex aspects of care at high-volume centers, almost a quarter of patients, many of whom reside in rural counties, will not have access to those centers or receive guideline-based care. OBJECTIVE: To explore the association between proximity of residential zip code to a high-volume cancer center with mortality and survival for patients with ovarian cancer. METHODS: The National Cancer Database was queried for cases of newly diagnosed ovarian cancer between January 2004 and December 2015. Our predictor of interest was distance traveled for treatment. Our primary outcomes were 30-day mortality, 90-day mortality, and overall survival. The effect of treatment on survival was analyzed with the Kaplan-Meier method. Multiple logistic regression for binary outcomes and Cox proportional hazards regression for overall survival were used to assess the effect of distance on outcome, controlling for potential confounding variables. RESULTS: A total of 115 540 patients were included. There was no statistically significant difference in 30- or 90-day mortality among any of the travel distance categories. A statistically significant decrease in 30-day re-admission was found among patients who lived further away from the treating facility. A total of 105 529 patients were available for survival analysis, and survival curves significantly differed between distance strata (p<0.0001). The adjusted regression models demonstrated increased long-term mortality in patients who lived farther away from the treating facility after controlling for potential confounding. CONCLUSION: Although 30- and 90-day mortality do not differ by travel distance, worse survival is observed among women living >50 miles from a high-volume treatment facility. With a national policy shift toward centralization of complex care, a better understanding of the impact of distance on survival in patients with ovarian cancer is crucial. Our findings inform the practice of healthcare delivery, especially in rural settings.

Association of Beta Blocker Use With Bone Mineral Density in the Framingham Osteoporosis Study: A Cross-Sectional Study.

Some, but not all, prior observational studies have shown that beta blocker (BB) use is associated with lower fracture risk and higher bone mineral density (BMD). Rodent studies show the mechanism to involve the reduction in the effects of beta-adrenergic signaling on bone remodeling. Because previous studies did not have detailed information on dose, duration, and beta-1 selectivity, we examined these in a cross-sectional analysis of the association between BB use and hip and spine BMD using DXA with the Offspring Cohort of the Framingham Heart Study. The sample size was n = 1520, and 397 individuals used BBs. We used propensity score modeling to balance a comprehensive set of covariates using inverse probability of treatment weighting (IPTW) to minimize bias due to treatment indication. We found significant differences in BMD between BB users and non-users for three of four BMD measurements (femoral neck: 3.1%, 95% CI, 1.1% to 5.0%; total femur: 2.9%, 95% CI, 0.9% to 4.9%; femoral trochanter: 2.4%, 95% CI, -0.1% to 5.0%; and lumbar spine: 2.7%, 95% CI, 0.2% to 5.0%). Results were found to be similar between sexes although the magnitude of association was larger for women. Similar differences were estimated for beta-1 selective and nonselective BBs compared with no BB use. We modeled dose in categories (no BB use, low-dose, high-dose) and as a continuous variable and found an increasing dose response that levels off at higher doses. Finally, associations were similar for short-term versus long-term (≤4 years versus >4 years) use. In summary, this large comprehensive study shows that BB use is associated with higher BMD in a dose-related manner regardless of beta-1 specificity and duration of use, which supports the conduct of a randomized clinical trial of BBs for achieving improvements in BMD for individuals at risk of bone loss with aging. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Area Deprivation Index and Rurality in Relation to Lung Cancer Prevalence and Mortality in a Rural State.

BACKGROUND: We sought to describe lung cancer prevalence and mortality in relation to socioeconomic deprivation and rurality. METHODS: We conducted a population-based cross-sectional analysis of prevalent lung cancers from a statewide all-payer claims dataset from 2012 to 2016, lung cancer deaths in Maine from the state death registry from 2012 to 2016, rurality, and area deprivation index (ADI), a geographic area-based measure of socioeconomic deprivation. Analyses examined rate ratios for lung cancer prevalence and mortality according to rurality (small and isolated rural, large rural, or urban) and ADI (quintiles, with highest reflecting the most deprivation) and after adjusting for age, sex, and area-level smoking rates as determined by the Behavioral Risk Factor Surveillance System. RESULTS: Among 1 223 006 adults aged 20 years and older during the 5-year observation period, 8297 received lung cancer care, and 4616 died. Lung cancer prevalence and mortality were positively associated with increasing rurality, but these associations did not persist after adjusting for age, sex, and smoking rates. Lung cancer prevalence and mortality were positively associated with increasing ADI in models adjusted for age, sex, and smoking rates (prevalence rate ratio for ADI quintile 5 compared with quintile 1 = 1.41, 95% confidence interval [CI] =1.30 to 1.54) and mortality rate ratio = 1.59, 95% CI = 1.41 to 1.79). CONCLUSION: Socioeconomic deprivation, but not rurality, was associated with higher lung cancer prevalence and mortality. Interventions should target populations with socioeconomic deprivation, rather than rurality per se, and aim to reduce lung cancer risk via tobacco treatment and control interventions and to improve patient access to lung cancer prevention, screening, and treatment services.

Association between the food and physical activity environment, obesity, and cardiovascular health across Maine counties.

BACKGROUND: Accounting for nearly one-third of all deaths, cardiovascular disease is the leading cause of mortality and morbidity in the United States. Adverse health behaviors are major determinants of this high incidence of disease. Examining local food and physical activity environments and population characteristics in a poor, rural state may highlight underlying drivers of these behaviors. We aimed to identify demographic and environmental factors associated with both obesity and overall poor cardiovascular health (CVH) behaviors in Maine counties. METHODS: Our cross-sectional study analyzed 40,398 Behavioral Risk Factor Surveillance System (BRFSS) 2011-2014 respondents alongside county-level United States Department of Agriculture (USDA) Food Environment Atlas 2010-2012 measures of the built environment (i.e., density of restaurants, convenience stores, grocery stores, and fitness facilities; food store access; and county income). Poor CVH score was defined as exhibiting greater than 5 out of the 7 risk factors defined by the American Heart Association (current smoking, physical inactivity, obesity, poor diet, hypertension, diabetes, and high cholesterol). Multivariable logistic regression models described the contributions of built environment variables to obesity and overall poor CVH score after adjustment for demographic controls. RESULTS: Both demographic and environmental factors were associated with obesity and overall poor CVH. After adjustment for demographics (age, sex, personal income, and education), environmental characteristics most strongly associated with obesity included low full-service restaurant density (OR 1.34; 95% CI 1.24-1.45), low county median household income (OR 1.31; 95% CI 1.21-1.42) and high convenience store density (OR 1.21; 95% CI 1.12-1.32). The strongest predictors of overall poor CVH behaviors were low county median household income (OR 1.30; 95% CI 1.13-1.51), low full-service restaurant density (OR 1.38; 95% CI 1.19-1.59), and low fitness facility density (OR 1.27; 95% CI 1.11-1.46). CONCLUSIONS: In a rural state, both demographic and environmental factors predict overall poor CVH. These findings may help inform communities and policymakers of the impact of both social determinants of health and local environments on health outcomes.

Association Between Rurality and Lung Cancer Treatment Characteristics and Timeliness.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in the United States, and rural states bear a greater burden of disease. METHODS: We analyzed tumor registry data to examine relationships between rurality and lung cancer stage at diagnosis and treatment. Cases were from the Maine Cancer Registry from 2012 to 2015, and rurality was defined using rural-urban commuting areas. Multivariable models were used to examine the relationships between rurality and treatment, adjusting for age, sex, poverty, education, insurance status, and cancer stage. RESULTS: We identified 5,338 adults with incident lung cancer; 3,429 (64.2%) were diagnosed at a late stage (III or IV). Rurality was not associated with stage at diagnosis. For patients with early-stage disease (I or II), rurality was not associated with receipt of treatment. However, for patients with late-stage disease, residents of large rural areas received more surgery (10%) compared with metropolitan (9%) or small/isolated rural areas (6%), P = .01. In multivariable analyses, patients in large rural areas received more chemotherapy (OR 1.48; 95% CI: 1.08-2.02) than those in metropolitan areas. Patients with early-stage disease residing in small/ isolated rural areas had delays in treatment (median time to first treatment = 43 days, interquartile range [IQR] 22-68) compared with large rural (34 days, IQR 17-55) and metropolitan areas (35 days, IQR 17-60), P = .0009. CONCLUSION: Rurality is associated with differences in receipt of specific lung cancer treatments and in timeliness of treatment.

Behavioral Risk Factors and Regional Variation in Cardiovascular Health Care and Death.

INTRODUCTION: Reducing the burden of death from cardiovascular disease includes risk factor reduction and medical interventions. METHODS: This was an observational analysis at the hospital service area (HSA) level, to examine regional variation and relationships between behavioral risks, health services utilization, and cardiovascular disease mortality (the outcome of interest). HSA-level prevalence of cardiovascular disease behavioral risks (smoking, poor diet, physical inactivity) were calculated from the Behavioral Risk Factor Surveillance System; HSA-level rates of stress tests, diagnostic cardiac catheterization, and revascularization from a statewide multi-payer claims data set from Maine in 2013 (with 606,260 patients aged ≥35 years), and deaths from state death certificate data. Analyses were done in 2016. RESULTS: There were marked differences across 32 Maine HSAs in behavioral risks: smoking (12.4%-28.6%); poor diet (43.6%-73.0%); and physical inactivity (16.4%-37.9%). After adjustment for behavioral risks, rates of utilization varied by HSA: stress tests (28.2-62.4 per 1,000 person-years, coefficient of variation=17.5); diagnostic cardiac catheterization (10.0-19.8 per 1,000 person-years, coefficient of variation=17.3); and revascularization (4.6-6.2 per 1,000 person-years; coefficient of variation=9.1). Strong HSA-level associations between behavioral risk factors and cardiovascular disease mortality were observed: smoking (R2=0.52); poor diet (R2=0.38); and physical inactivity (R2=0.35), and no association between revascularization and cardiovascular disease mortality after adjustment for behavioral risk factors (R2=0.02). HSA-level behavioral risk factors were also strongly associated with all-cause mortality: smoking (R2=0.57); poor diet (R2=0.49); and physical inactivity (R2=0.46). CONCLUSIONS: There is substantial regional variation in behavioral risks and cardiac utilization. Behavioral risk factors are associated with cardiovascular disease mortality regionally, whereas revascularization is not. Efforts to reduce cardiovascular disease mortality in populations should focus on prevention efforts targeting modifiable risk factors.

Variations in Hospice Utilization and Length of Stay for Medicare Patients With Melanoma.

CONTEXT: Timely hospice referral is an indicator of high-quality end-of-life care for cancer patients. Variations in patient characteristics associated with hospice utilization and length of stay have been demonstrated in studies of other malignancies but not melanoma. OBJECTIVES: We sought to understand hospice utilization and patient characteristics associated with variability in use for the older melanoma population. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify 13,393 melanoma patients aged 65+ years at time of diagnosis between 2000 and 2009, who died by 12/31/10. The primary outcome was enrollment in hospice with secondary outcome of hospice duration. Patient characteristics associated with variations in hospice enrollment were examined. RESULTS: Among 13,393 patients who died with melanoma, 5298 (40%) received hospice care. Of these, 17% were enrolled in hospice for three days or less, while 13% had ≥90 days of hospice care. Despite improvements over time in the proportion of patients who received hospice and those who received at least 90 days of hospice care, late hospice enrollments did not change. Multivariable analysis revealed that patients of older age, with distant disease at time of diagnosis, and residing in rural areas or in census tracts with higher rates of high school completion were more likely to enroll in hospice. CONCLUSION: Rates of hospice enrollment increased over time but remained under accepted quality benchmarks with variations evident in those who receive hospice services. Efforts to increase access to earlier hospice care for all patients dying with melanoma are essential.

Cancer incidence in patients with hereditary hemorrhagic telangiectasia.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by deficiency in endoglin, an angiogenic protein. We previously showed that HHT, in which systemic endoglin expression is reduced, was associated with better survival outcomes in cancer patients (Duarte et al. in Cancer Epidemiol Biomarkers Prev 23:117-125, 2014). Here, we evaluated whether HHT was associated with reduced cancer incidence. METHODS: A matched case-control analysis using SEER Medicare was conducted to evaluate the effect of HHT on diagnosis with breast, colorectal, lung, or prostate cancer between 2000 and 2007 (n = 633,162). Cancer and non-cancer patients were matched on age, sex, SEER registry region, and length of the ascertainment period for HHT. We assessed crude association using a McNemar's test and then adjusted for demographic variables, cancer type, cancer stage, comorbidities, and ascertainment period with a conditional logistic regression model for cancer incidence. RESULTS: The McNemar's test showed no significant association between HHT and cancer incidence (p = 0.74). Adjusting for covariates with the conditional logistic regression model did not change the result [HHT odds ratio 0.978; 95 % CI (0.795, 1.204)]. The lack of association between HHT and cancer incidence is unexpected given the previously discovered significant association between HHT and improved survival outcomes (Duarte et al. in Cancer Epidemiol Biomarkers Prev 23:117-125, 2014). CONCLUSIONS: We conclude that the protective effect of reduced systemic endoglin expression in cancer is specific to cancer progression through its effect on vascularization and other stromal effects but does not extend to cancer initiation.

Tolerability and Efficacy of 3 Approaches to Intra-articular Corticosteroid Injections of the Knee for Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: Several studies have been performed suggesting that a superolateral approach to cortisone injections for symptomatic osteoarthritis of the knee is more accurate than anteromedial or anterolateral approaches, but there are little data to correlate clinical outcomes with these results. Additionally, there are minimal data to evaluate the pain of such procedures, and this consideration may impact physician preferences for a preferred approach to knee injection. PURPOSE: To determine the comparative efficacy and tolerability (patient comfort) of landmark-guided cortisone injections at 3 commonly used portals into the arthritic knee without effusion. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Adult, English-speaking patients presenting to a sports medicine clinic with knee pain attributed to radiographically proven grades I through III knee osteoarthritis were randomized to receive a cortisone injection via superolateral, anteromedial, or anterolateral approaches. Patients used a visual analog scale (VAS) to self-report comfort with the procedure. Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 VAS scores were used to establish baseline pain and dysfunction prior to the injection and at 1 and 4 weeks follow-up via mail. RESULTS: A total of 55 knees from 53 patients were randomized for injection using a superolateral approach (17 knees), an anteromedial approach (20 knees), and an anterolateral approach (18 knees). The mean VAS scores for procedural discomfort showed no significant differences between groups (superolateral, 39.1 ± 28.5; anteromedial, 32.9 ± 31.5; anterolateral, 33.1 ± 26.6; P = .78). WOMAC scores at baseline were similar between groups as well (superolateral, 1051 ± 686; anteromedial, 1450 ± 573; anterolateral, 1378 ± 673; P = .18). The WOMAC scores decreased at 1 and 4 weeks for all groups, with no significant differences in reduction between the 3 groups. CONCLUSION: Other studies have shown that the superolateral portal is the most accurate. This study did not assess accuracy, but it showed that all 3 knee injection sites studied have similar overall clinical benefit at 4-week follow-up. Procedural pain was not significantly different between groups.