Outreach to primary care patients in lung cancer screening: A randomized controlled trial.

Current guidelines recommend annual lung cancer screening (LCS), but rates are low. The current study evaluated strategies to increase LCS. This study was a randomized controlled trial designed to evaluate the effects of patient outreach and shared decision making (SDM) about LCS among patients in four primary care practices. Patients 50 to 80 years of age and at high risk for lung cancer were randomized to Outreach Contact plus Decision Counseling (OC-DC, n = 314), Outreach Contact alone (OC, n = 314), or usual care (UC, n = 1748). LCS was significantly higher in the combined OC/OC-DC group versus UC controls (5.5% vs. 1.8%; hazard ratio, HR = 3.28; 95% confidence interval, CI: 1.98 to 5.41; p = 0.001). LCS was higher in the OC-DC group than in the OC group, although not significantly so (7% vs. 4%, respectively; HR = 1.75; 95% CI: 0.86 to 3.55; p = 0.123). LCS referral/scheduling was also significantly higher in the OC/OC-DC group compared to controls (11% v. 5%; odds ratio, OR = 2.02; p = 0.001). We observed a similar trend for appointment keeping, but the effect was not statistically significant (86% v. 76%; OR = 1.93; p = 0.351). Outreach contacts significantly increased LCS among primary care patients. Research is needed to assess the additional value of SDM on screening uptake.

Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors.

PURPOSE: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2-/cHER2+ can benefit from anti-HER2 targeted therapies. METHODS: cHER2 status was determined in 105 advanced-stage patients with tHER2- breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan-Meier method. RESULTS: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20-3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10-0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36-1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). CONCLUSION: In advanced-stage breast cancer patients with tHER2- tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

Predictors of overall and test-specific colorectal Cancer screening adherence.

This study investigated predictors of overall and test-specific colorectal cancer screening (CRCS). Stool blood test (SBT) and/or colonoscopy screening were offered to primary care patients in two randomized controlled trials which assessed the impact of behavioral interventions on screening. Data were obtained through surveys and electronic medical records. Among 1942 participants, 646 (33%) screened. Exposure to interventions was associated with higher overall CRCS by twofold to threefold; older age, African American race, being married, and having a higher screening decision stage were also associated with higher overall CRCS (odds ratios = 1.30, 1.31, 1.34, and 5.59, respectively). Intervention, older age, female gender, and being married were associated with higher SBT adherence, while preference for colonoscopy was associated with lower SBT adherence. Intervention and higher decision stage were associated with higher colonoscopy adherence, while preference for SBT was associated with lower colonoscopy adherence. Among older individuals, African Americans had higher overall CRCS than whites, but this was not true among younger individuals (interaction p = .041). The higher screening adherence of African Americans over whites was due to stronger screening with a non-preferred test, i.e., higher SBT adherence only among individuals who preferred colonoscopy and higher colonoscopy adherence only among individuals who preferred SBT. Intervention exposure, sociodemographic background, and screening decision stage predicted overall CRCS adherence. Gender and test preference also affected test-specific screening adherence. Interactions involving race and test preference suggest that it is important to provide both colonoscopy and SBT screening options to patients, particularly African Americans.

Telephone-Based Shared Decision-making for Lung Cancer Screening in Primary Care.

The national rate of  lung cancer screening, approximately 3-5%, is too low and strategies which include shared decision-making and increase screening are needed. A feasibility study in one large primary care practice of telephone-based delivery of decision support via an online tool, the Decision Counseling Program© (DCP) was administered to patients eligible for lung cancer screening according to USPSTF screening guidelines. We collected data on demographics, decisional conflict, and conducted chart audits to ascertain screening. From electronic medical record data, we identified 829 age-eligible current or former smokers. Of the 297 individuals reached, 54 were eligible and 28 were recruited to the study and 20 underwent the DCP© intervention. Participants in the intervention were more likely to complete low-dose CT scans at 90 days. Current smokers were less likely to complete the DCP. Women were less likely to complete LDCT. This non-persuasive, high-quality shared decision-making intervention significantly increased lung cancer screening and was feasible in real-world clinical care. This intervention offers a promising model whereby patients can be supported in a decision, based on their values and beliefs while also supporting gains in lung cancer screening.

Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

Prospective and longitudinal evaluations of telomere length of circulating DNA as a risk predictor of hepatocellular carcinoma in HBV patients.

Prospective and longitudinal epidemiological evidence is needed to assess the association between telomere length and risk of hepatocellular carcinoma (HCC). In 323 cancer-free Korean-American HBV patients with 1-year exclusion window (followed for >1 year and did not develop HCC within 1 year), we measured the relative telomere length (RTL) in baseline serum DNAs and conducted extensive prospective and longitudinal analyses to assess RTL-HCC relationship. We found that long baseline RTL conferred an increased HCC risk compared to short RTL [hazard ratio (HR) = 4.93, P = 0.0005). The association remained prominent when the analysis was restricted to patients with a more stringent 5-year exclusion window (HR = 7.51, P = 0.012), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Adding baseline RTL to demographic variables increased the discrimination accuracy of the time-dependent receiver operating characteristic analysis from 0.769 to 0.868 (P = 1.0 × 10-5). In a nested longitudinal subcohort of 16 matched cases-control pairs, using a mixed effects model, we observed a trend of increased RTL in cases and decreased RTL in controls along 5 years of follow-up, with a significant interaction of case/control status with time (P for interaction=0.002) and confirmed the association between long RTL and HCC risk [odds ratio [OR] = 3.63, P = 0.016]. In summary, serum DNA RTL may be a novel non-invasive prospective marker of HBV-related HCC. Independent studies are necessary to validate and generalize this finding in diverse populations and assess the clinical applicability of RTL in HCC prediction.

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study.

BACKGROUND & AIMS: We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. METHODS: We collected data from the Surveillance, Epidemiology, and End Results-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) (P < .0001); this value decreased significantly, to 5.0% (P < .0001), after patients were matched for tumor presentation, and decreased to 4.9% (P < .0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P = .0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P = .090) after tumor presentation match, but was not reduced further after treatment match. CONCLUSIONS: We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer.

Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer.

PURPOSE: Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication. METHODS: CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients. The associations between baseline, first follow-up, and longitudinal enumerations of CTCs and CTC-clusters with patient progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. RESULTS: CTC and CTC-cluster counts at both baseline and first follow-up were significantly associated with patient PFS and OS. Time-dependent analysis of longitudinally collected samples confirmed the significantly unfavorable PFS and OS in patients with ≥5 CTCs, and further demonstrated the independent prognostic values by CTC-clusters compared to CTC-enumeration alone. Longitudinal analyses also identified a link between the size of CTC-clusters and patient OS: compared to the patients without any CTC, those with 2-cell CTC-clusters and ≥3-cell CTC-clusters had a hazard ratio (HR) of 7.96 [95 % confidence level (CI) 2.00-31.61, P = 0.003] and 14.50 (3.98-52.80, P < 0.001), respectively. CONCLUSIONS: In this novel time-dependent analysis of longitudinally collected CTCs and CTC-clusters, we showed that CTC-clusters added additional prognostic values to CTC enumeration alone, and a larger-size CTC-cluster conferred a higher risk of death in MBC patients.

Taxonomy for colorectal cancer screening promotion: Lessons from recent randomized controlled trials.

OBJECTIVE: To derive a taxonomy for colorectal cancer screening that advances Randomized Controlled Trials (RCTs) and screening uptake. DESIGN: Detailed publication review, multiple interviews with principal investigators (PIs) and collaboration with PIs as co-authors produced a CRCS intervention taxonomy. Semi-structured interview questions with PIs (Drs. Inadomi, Myers, Green, Gupta, Jerant and Ritvo) yielded details about trial conduct. Interview comparisons led to an iterative process informing serial interviews until a consensus was obtained on final taxonomy structure. RESULTS: These taxonomy headings (Engagement Sponsor, Population Targeted, Alternative Screening Tests, Delivery Methods, and Support for Test Performance (EPADS)) were used to compare studies. Exemplary insights emphasized: 1) direct test delivery to patients; 2) linguistic-ethnic matching of staff to minority subjects; and 3) authorization of navigators to schedule or refer for colonoscopies and/or distribute stool blood tests during screening promotion. CONCLUSION: PIs of key RCTs (2012-2015) derived a CRCS taxonomy useful in detailed examination of CRCS promotion and design of future RCTs.

What is a good medical decision? A research agenda guided by perspectives from multiple stakeholders.

Informed and shared decision making are critical aspects of patient-centered care, which has contributed to an emphasis on decision support interventions to promote good medical decision making. However, researchers and healthcare providers have not reached a consensus on what defines a good decision, nor how to evaluate it. This position paper, informed by conference sessions featuring diverse stakeholders held at the 2015 Society of Behavioral Medicine and Society for Medical Decision Making annual meetings, describes key concepts that influence the decision making process itself and that may change what it means to make a good decision: interpersonal factors, structural constraints, affective influences, and values clarification methods. This paper also proposes specific research questions within each of these priority areas, with the goal of moving medical decision making research to a more comprehensive definition of a good medical decision, and enhancing the ability to measure and improve the decision making process.

A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients.

BACKGROUND: We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption. METHODS: We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results. RESULTS: Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using the new prognostic test. Multivariable analyses showed that physicians in academic medical centers were significantly more receptive to molecular test use than those in non-academic settings. Forty-one percent of respondents were ready to act on abnormal molecular test results. Physicians who viewed current staging methods as inaccurate and were confident in their capacity to incorporate molecular testing in practice were more likely to say they would act on abnormal test results. CONCLUSIONS: Physician receptivity to molecular diagnostic testing for early-stage colon cancer patients is likely to be influenced by practice setting and perceptions related to delivering quality care to patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01972737.

Modeling the overall survival of patients with advanced-stage non-small cell lung cancer using data of routine laboratory tests.

Cancer patients undergo routine clinical monitoring with an array of blood tests that may carry long-term prognostic information. We aimed to develop a new prognostic model predicting survival for patients with advanced non-small cell lung cancer (NSCLC), based on laboratory tests commonly performed in clinical practice. A cohort of 1,161 stage IIIB or IV NSCLC patients was divided into training (n = 773) and testing (n = 388) cohorts. We analyzed the associations of 32 commonly tested laboratory variables with patient survival in the training cohort. We developed a model based on those significant laboratory variables, together with important clinical variables. The model was then evaluated in the testing cohort. Five variables, including albumin, total protein, alkaline phosphatase, blood urea nitrogen and international normalized ratio, were significantly associated with patient survival after stepwise selection. A model incorporating these variables classified patients into low-, medium- and high-risk groups with median survival of 16.9, 7.2 and 2.1 months, respectively (p < 0.0001). Compared with low-risk group, patients in the medium- and high-risk groups had a significantly higher risk of death at 1 year, with hazard ratio (HR) of 1.95 (95% CI 1.62-2.36) and 5.22 (4.30-6.34), respectively. These results were validated in the testing cohort. Overall, we developed a prognostic model relying entirely on readily available variables, with similar predictive power to those which depend on more specialized and expensive molecular assays. Further study is necessary to validate and further refine this model, and compare its performance to models based on more specialized and expensive testing.

The effects of erythropoiesis-stimulating agents on the short-term and long-term survivals in metastatic breast cancer patients receiving chemotherapy: a SEER population-based study.

Current clinical guidelines state that the use of erythropoiesis-stimulating agents (ESAs) may be considered to treat chemotherapy-induced anemia in the non-curative setting to alleviate anemia-related symptoms. However, no convincing survival benefit has been demonstrated to support the use of ESAs in these patients. Using the comprehensive data collected in the National Cancer Institute (NCI)-surveillance epidemiology and end results (SEER) and Medicare-linked database, we analyzed the effect of ESA use on the short-term (18-month) and long-term (60-month) survival rates of chemotherapy-treated metastatic breast cancer patients. Confounding variables were adjusted using a propensity score approach. We also analyzed the effects of ESA on the survival of patients receiving trastuzumab, a commonly prescribed targeted therapy agent in treating HER2-positive tumors. Metastatic breast cancer patients who received ESA treatment exhibited similar 60-month survival rate to those without ESA treatment (22.8 vs. 24.9%, p = 0.8). ESA-treated patients had a trend toward better 18-month survival [crude hazard ratio (HR) 0.86, 95% confidence intervals (CI) 0.68-1.09, p = 0.21]. This protective effect during the first 18 months of chemotherapy became marginally significant after adjusting for the propensity of receiving ESAs (HR 0.80, 95% CI 0.63-1.01, p = 0.070). An interaction effect between ESA and trastuzumab on patient survival was noticeable but not statistically significant. ESAs did not negatively affect the long-term survival of metastatic breast cancer patients. Moreover, ESAs improved patients' survival during the first 18 months of chemotherapy treatment. These findings endorse the current clinical guideline. Given the short survival of these patients, the potential short-term beneficial effects of ESAs are clinically meaningful.

Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer.

The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients' progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57-4.86, P log-rank = 0.0005] and 2.83 (1.48-5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02-4.78) and 3.32 (1.68-6.55), respectively (P log-rank = 0.0006, P trend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.

Racial disparity in breast cancer survival: the impact of pre-treatment hematologic variables.

PURPOSE: A survival disparity of black versus white breast cancer patients has been extensively documented but not adequately explained. Blacks and whites also have significant differences in hematologic traits including hemoglobin (HGB). However, a link between survival disparity and hematologic differences has not been reported. We aimed to explore the effect of pre-treatment hematologic variables on this survival disparity. METHODS: We sequentially matched 443 black patients, using a minimum distance approach, to four different sets of 443 whites on demographics (age, year of diagnosis, smoking, and drinking status), tumor presentation (all demographic variables plus tumor stage, grade, and hormone receptor status), treatment (all presentation variables plus surgery, chemotherapy, radiation therapy, and hormone therapy), and presentation plus pre-treatment hematologic variables. Racial survival for each matched dataset was analyzed by Cox proportional hazards model. RESULTS: We found that white patients matched on demographic characteristics had more favorable survival than blacks [hazard ratio (HR) 0.57, 95 % confidence interval (CI) 0.42-0.77, p log-rank = 0.0002]. Presentation match diminished this disparity [HR 0.72 (0.54-0.95), p log-rank = 0.0199], which was not further reduced in treatment match [HR 0.73 (0.55-0.96), p log-rank = 0.0249]. However, the survival disparity was largely reduced when pre-treatment level of HGB or red blood cell distribution width was further matched in addition to presentation match [HR 0.83 (0.64-1.09), p log-rank = 0.1819 and HR 0.83 (0.64-1.09), p log-rank = 0.1760, respectively]. CONCLUSIONS: We found that in our patient population, differences in tumor presentation and certain pre-treatment hematologic traits, but not treatment, were associated with the survival disparity between black and white breast cancer patients.

Aspartate aminotransferase to platelet ratio index as a prospective predictor of hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIM: APRI (aspartate aminotransferase [AST] to platelet ratio index) is widely used to assess fibrosis and cirrhosis risk, especially in hepatitis C virus (HCV)-infected patients. Few studies have evaluated APRI and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk. Prospective evidence is needed to assess whether APRI predicts HCC risk in HBV patients. METHOD: In a prospectively enrolled clinical cohort of 855 HBV patients with a 1-year exclusion window (followed for > 1 year and did not develop HCC within 1 year), the predictive value of APRI in HCC risk was evaluated by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. RESULTS: Higher APRI prospectively conferred a significantly increased risk of HCC in univariate analysis (quartile analysis, P trend = 2.9 × 10(-7) ). This effect remained highly significant after adjusting for common host characteristics but not cirrhosis (P trend = 7.1 × 10(-5) ), and attenuated when cirrhosis is adjusted (P trend = 0.021). The effect remained prominent when the analysis was restricted to patients with a more stringent 2-year exclusion window (P trend = 0.008 in quartile analysis adjusting all characteristics including cirrhosis), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Longitudinal comparison demonstrated a persistently higher APRI value in HBV patients who developed HCC during follow-up than those remaining cancer free. CONCLUSION: APRI might be a marker of HCC risk in HBV patients in cirrhosis-dependent and -independent manners. Further studies are warranted to validate this finding and test its clinical applicability in HCC prevention.

Circulating mitochondrial DNA content associated with the risk of liver cirrhosis: a nested case-control study.

BACKGROUND AND AIMS: Accumulating evidence has indicated that variations of mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular carcinoma (HCC). However, no study has been conducted to evaluate the association of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of HCC. METHODS: We conducted a nested case-control study including 136 cirrhotic hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV controls. We determined mtDNA content in serum DNA using quantitative real-time PCR and analyzed its association with cirrhosis risk. RESULTS: We found that cirrhotic HBV patients had significantly lower levels of mtDNA content than non-cirrhotic HBV controls (P = 0.0184). Compared to patients with high mtDNA content, those with low mtDNA content had a 2.25-fold increased risk of cirrhosis [odds ratio (OR) 2.25, 95 % confidence interval (CI) 1.26-4.02]. This association exhibited a significant dose relationship as evidenced in both tertile and quartile analyses (P for trend = 0.0018 and 0.0008, respectively). Stratified analyses showed that the association was prominent in younger patients (P = 0.0122), males (P = 0.0069), never smokers (P = 0.0063), never drinkers (P = 0.0078), patients with a family history of HBV infection (P = 0.0062), and patients with low values of aspartate aminotransferase to platelet ratio index (APRI), a commonly used noninvasive marker for cirrhosis (P = 0.0109). Moreover, a joint effect was observed between low mtDNA content and high APRI values on cirrhosis risk (OR 24.07, 95 % CI 6.72-86.24). CONCLUSIONS: Low circulating mtDNA content may confer an increased cirrhosis risk in HBV patients. Further prospective studies are warranted to validate these findings and explore the clinical significance.

Effects of genetic and environmental risk assessment feedback on colorectal cancer screening adherence.

Little is known about the impact of genetic and environmental risk assessment (GERA) feedback on colorectal cancer (CRC) screening. In a recently completed randomized trial, primary care patients received GERA feedback based on a blood test for genetic polymorphisms and serum folate level (GERA Group) versus usual care (Control Group). Subsequently, participants were offered CRC screening. Among participants who received GERA feedback, being at elevated risk was negatively associated with prospective CRC screening adherence. Secondary analyses of data from this study were performed to identify independent predictors of adherence among participants who received GERA feedback. We obtained baseline survey, follow-up survey, and endpoint medical records data on sociodemographic background, knowledge, psychosocial characteristics, risk status, and adherence for 285 GERA Group participants. Univariate and multivariable analyses were performed to identify predictors of CRC screening adherence. Following a 6-month outcomes observation period, we also conducted two focus groups with GERA Group participants to assess their perceptions of GERA risk feedback and screening. Content analyses of focus group data were evaluated to gain insights into participant response to risk feedback. Overall, half of GERA Group participants adhered to screening within 6 months after randomization. Multivariable analyses showed a statistically significant interaction between race and GERA feedback status relative to screening adherence (p = 0.043). Among participants who received average risk feedback, adherence was comparable among whites (49.7 %) and nonwhites (54.1 %); however, among those at elevated risk, adherence was substantially higher among whites (66.7 %) compared to nonwhites (33.3 %). Focus group findings suggest that whites were more likely than nonwhites to view elevated risk feedback as a prompt to screen. In response to receiving elevated risk feedback, nonwhites were more likely than whites to report feeling anxiety about the likelihood of being diagnosed with CRC. Further research is needed to explore race-related CRC screening differences in response to GERA feedback.

Genetic and environmental risk assessment and colorectal cancer screening in an average-risk population: a randomized trial.

BACKGROUND: New methods are needed to improve health behaviors, such as adherence to colorectal cancer (CRC) screening. Personalized genetic information to guide medical decisions is increasingly available. Whether such information motivates behavioral change is unknown. OBJECTIVE: To determine whether individualized genetic and environmental risk assessment (GERA) of CRC susceptibility improves adherence to screening in average-risk persons. DESIGN: 2-group, randomized, controlled trial. (ClinicalTrials.gov: NCT0087360). SETTING: 4 medical school-affiliated primary care practices. PARTICIPANTS: 783 participants at average risk for CRC who were not adherent to screening at study entry. INTERVENTION: Participants were randomly assigned to usual care or GERA, which evaluated methylenetetrahydrofolate reductase polymorphisms and serum folate levels. On the basis of prespecified combinations of polymorphisms and serum folate levels, GERA recipients were told that they were at elevated or average risk for CRC. MEASUREMENTS: The primary outcome was CRC screening within 6 months of study entry. RESULTS: Overall screening rates for CRC did not statistically significant differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]). LIMITATION: Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed. CONCLUSION: In average-risk persons, CRC screening uptake was not positively associated with feedback from a single personalized GERA. Additional studies will be required to evaluate whether other approaches to providing GERA affect screening utilization differently. These findings raise concern about the effectiveness of moderately predictive assessment of genetic risk to promote favorable health care behavior. PRIMARY FUNDING SOURCE: National Institutes of Health.