Brief Report: Recent Methamphetamine Use Is Associated With Increased Rectal Mucosal Inflammatory Cytokines, Regardless of HIV-1 Serostatus.

BACKGROUND: Methamphetamine use increases the risk of HIV-1 infection among seronegative users and can exacerbate disease progression in HIV-positive users. The biological mechanisms underlying these associations remain unclear. In this cross-sectional pilot study, we examine the associations between recent methamphetamine use and inflammation in the rectal mucosa and peripheral blood compartments in HIV-1 seropositive and seronegative men who have sex with men. METHODS: HIV-seronegative and HIV-seropositive men who have sex with men participants were enrolled (N = 24). Recent methamphetamine use was determined by urine drug screen. Cytokines were quantified using multiplex arrays from collected plasma and rectal sponge samples, and peripheral blood T-cell activation was assessed by flow cytometry. RESULTS: Methamphetamine use was associated with consistently increased rectal inflammatory cytokines, specifically interleukin-6 and tumor necrosis factor-alpha, regardless of HIV-1 serostatus in this pilot study. This association was significant after adjusting for age, HIV-serostatus, and receptive anal intercourse frequency using regression analysis. Similar increases were not uniformly observed in peripheral blood. CONCLUSIONS: Methamphetamine use is associated with increased local mucosal inflammatory cytokine production. These findings may help explain the increased HIV-1 risk seen in methamphetamine users and contribute to increased inflammation among HIV-seropositive users.

Markers of Immune Activation and Inflammation, and Non-Hodgkin Lymphoma: A Meta-Analysis of Prospective Studies.

BACKGROUND: Chronic inflammation and immune activation are reported to play a key role in the etiology of non-Hodgkin lymphoma (NHL). We conducted a meta-analysis on the associations between prediagnosis circulating levels of immune stimulatory markers, interleukin 6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), CXCL13, soluble CD23 (sCD23), sCD27, sCD30, and the risk of NHL. METHODS: Relevant studies were identified from PubMed, EMBASE, and Web of Science up to January 1, 2017. We calculated summary odds ratio (OR) estimates for the association between one natural log increase in concentration of each biomarker and NHL using random-effects models for NHL as a composite outcome and for several histological subtypes of NHL. RESULTS: Seventeen nested case control studies were included. Elevated levels of several biomarkers were more strongly associated with increased odds of NHL: TNF-α, OR = 1.18 (95% confidence interval [CI] = 1.04 to 1.34); CXCL13, OR = 1.47 (95% CI = 1.03 to 2.08); sCD23, OR = 1.57 (95% CI = 1.21 to 2.05); sCD27, OR = 2.18 (95% CI = 1.20 to 3.98); sCD30, OR = 1.65 (95% CI = 1.22 to 2.22). In stratified analyses, IL-6, TNF-α, sCD27, and sCD30 were more strongly associated with NHL in HIV-infected individuals compared to HIV-uninfected individuals. Between-study heterogeneity was observed across multiple biomarkers for overall NHL and by subtypes. CONCLUSION: This meta-analysis provides evidence that elevated circulating levels of TNF-α, CXCL13, sCD23, sCD27, and sCD30 are consistently associated with an increased risk of NHL, suggesting the potential utility of these biomarkers in population risk stratification and prediction.

HLA and Risk of Diffuse Large B cell Lymphoma After Solid Organ Transplantation.

BACKGROUND: Solid organ transplant recipients have heightened risk for diffuse large B cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established. METHODS: We examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number. RESULTS: Compared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [95% CI], 0.61-0.95; one: IRR, 0.83; 95% CI, 0.69-1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all 3 loci (P = 0.0003). Several individual recipient HLA-A, -B, -C, -DR, and -DQ antigens were also associated with DLBCL risk, including DR13 (IRR, 0.74; 95% CI, 0.57-0.93) and B38 (IRR, 1.48; 95% CI, 1.10-1.93), confirming prior findings that these 2 antigens are associated with risk of infection-associated cancers. CONCLUSIONS: In conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients or chronic immune stimulation.

Outcomes of a Tailored Intervention for Cigarette Smoking Cessation Among Latinos Living With HIV/AIDS.

INTRODUCTION: Tobacco use has emerged as a leading killer among persons living with HIV, with effective approaches to tobacco treatment still unknown. HIV infection is nearly 3 times as prevalent in Latinos than in non-Latino Whites. This study reports the results of a randomized trial comparing a tailored intervention to brief counseling for smoking cessation among Latino smokers living with HIV (LSLWH). METHODS: LSLWH (N = 302; 36% female, 10% employed full-time, 49% born in United States) were randomized to 4 in-person sessions of a tailored intervention (Aurora) or 2 in-person sessions of brief advice (enhanced standard care [ESC]). Both groups received 8 weeks of nicotine replacement therapy (NRT) patch. Biochemically validated 6- and 12-month 7-day point-prevalence abstinence (PPA) rates were compared, along with secondary outcomes (e.g., reduction to light smoking, NRT adherence). RESULTS: Seven-day PPA rates reached 8% versus 11% at 6 months and 6% versus 7% at 12 months, for Aurora and ESC, respectively, with no between-group differences (p values > .40). Significant changes from baseline to 6 and 12 months among intervention targets were noted (percentage reduction in heavy smoking and dependence; increases in knowledge and self-efficacy). Baseline smoking frequency, older age, and higher intensity of patch use during the trial emerged as significant predictors of abstinence at 6 months. CONCLUSIONS: There was no evidence that the tailored intervention improved cessation rates. Interventions that encourage use of, and adherence to, empirically validated cessation aids require further development to reduce tobacco-related death and disease in this vulnerable population.

Preliminary Development and Evaluation of an Algorithm to Identify Breast Cancer Chemotherapy Toxicities Using Electronic Medical Records and Administrative Data.

PURPOSE: Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization. METHODS: The algorithm used administrative, pharmacy, and electronic data from outpatient, emergency room, and inpatient records of 99 women diagnosed with breast cancer from 2006 to 2009 who underwent chemotherapy. Data were abstracted for 12 months post-treatment initiation (24 months for trastuzumab recipients). An oncology nurse independently blindly reviewed records; these results were the "gold standard." Sensitivity and specificity were calculated for overall toxicity, categories of toxicities, and toxicity by age or regimen. The algorithm was applied to an independent sample of 1,575 patients with breast cancer diagnosed during the study period to estimate prevalence rates. RESULTS: The overall sensitivity for detecting chemotherapy-related toxicity was 89% (95% CI, 77% to 95%). The highest sensitivity was for identification of hematologic toxicities (97%; 95% CI, 84% to 99%). There were good sensitivities for infectious toxicity, but rates dropped for GI and neurological toxicities. Specificity was high within each category (89% to 99%), but when combined to measure any toxicity, it was lower (70%; 95% CI, 57% to 81%). When applied to an independent chemotherapy sample, the algorithm estimates a 26% rate of hematologic toxicity; rates were higher among patients age ≥ 65 years versus less than 65 years. CONCLUSIONS: If validated in other samples and health care settings, algorithms to capture toxicity could be useful in comparative and cost-effectiveness evaluations of community practice-delivered treatment.

Did changes in drug reimbursement after the medicare modernization act affect chemotherapy prescribing?

PURPOSE: The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). PATIENTS AND METHODS: We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. RESULTS: The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA. CONCLUSION: Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns.

Knowledge and willingness to provide research biospecimens among foreign-born Latinos using safety-net clinics.

Latinos tend to be under-represented in cancer research and in bio-repositories. We conducted a Spanish-language, interviewer-administered cross-sectional survey of 331 foreign-born Latinos from Central and South America attending safety-net clinics in order to describe factors associated with knowledge about and intention to provide bio-specimens for research purposes. We used logistic regression and multiple imputation methods to evaluate associations between socio-cultural measures, medical trust, demographics, as well as knowledge about and intentions to provide bio-specimens. Almost half (47 %) of respondents knew what bio-specimens were, and 67 % said that they would provide a specimen after being given information about what this involved; this increased to 72 % among those with prior knowledge. Controlling for covariates, Latinos with a high school education and above were more likely to know what a bio-specimen was and to say they would provide bio-specimens than were those with lower levels of education [adjusted OR (aOR) 2.85, 95 % CI 1.37-5.96; and 3.49, 95 % CI 1.41-8.63, p ≤ 0.01, respectively]. Those with greater social integration were more likely to know about bio-specimens than those with less integration (aOR 2.54, 95 % CI 1.45-4.46, p = 0.001). Higher endorsement of family values was independently associated with intent to give bio-specimens (aOR 1.11, 95 % CI 1.02-1.20, p = 0.017 per five-point increase in "familism" score). Medical mistrust was not related to intentions to provide specimens. Our results suggest that interventions to increase willingness to provide bio-specimens could leverage trusted clinics or social networks and should consider individuals' education and socio-cultural perspectives.

A planned, prospective comparison of short-term quality of life outcomes among older patients with breast cancer treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901.

OBJECTIVES: Patients ≥ 65 years old ("older") are often not included in randomized clinical trials (RCT), but when they are, care in an RCT might improve quality of life (QoL). We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study ("off-trial"). METHODS: Older women with invasive, non-metastatic breast cancer (n=150 RCT; 530 off-trial) were included. Linear mixed-effects models tested associations between chemotherapy on- vs. off-trial and changes in EORTC (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire) QoL scores over 24 months, controlling for pre-treatment QoL, age, education, tumor factors, comorbidity, and other covariates. RESULTS: Anthracycline regimens were used by 58% of women treated on-trial vs. 54% of those treated off-trial. Women in the RCT reported an adjusted mean increase of 13.7 points (95% CI 10.2, 17.1) in global QoL at 24 months (vs. mid-treatment), while women treated off-trial had only an adjusted improvement of 7.0 points (95% CI 3.5, 10.4; p=.007 for difference in mean changes). Women in the RCT had significantly greater improvement in emotional function than those treated off-trial, controlling for baseline; they also had greater reductions in therapy side effects and fatigue at 24 months than women off-trial, controlling for covariates. CONCLUSION: There may be different QoL trajectories for older women undergoing breast cancer chemotherapy on- vs. off-trial. If confirmed, the results suggest that the extra monitoring and communication within an RCT could provide the infrastructure for interventions to address symptoms and improve QoL for the growing older cancer population.

Physician self-reported treatment of brain metastases according to patients' clinical and demographic factors and physician practice setting.

BACKGROUND: Limited data guide radiotherapy choices for patients with brain metastases. This survey aimed to identify patient, physician, and practice setting variables associated with reported preferences for different treatment techniques. METHOD: 277 members of the American Society for Radiation Oncology (6% of surveyed physicians) completed a survey regarding treatment preferences for 21 hypothetical patients with brain metastases. Treatment choices included combinations of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. Vignettes varied histology, extracranial disease status, Karnofsky Performance Status (KPS), presence of neurologic deficits, lesion size and number. Multivariate generalized estimating equation regression models were used to estimate odds ratios. RESULTS: For a hypothetical patient with 3 lesions or 8 lesions, 21% and 91% of physicians, respectively, chose WBRT alone, compared with 1% selecting WBRT alone for a patient with 1 lesion. 51% chose WBRT alone for a patient with active extracranial disease or KPS=50%. 40% chose SRS alone for an 80 year-old patient with 1 lesion, compared to 29% for a 55 year-old patient. Multivariate modeling detailed factors associated with SRS use, including availability of SRS within one's practice (OR 2.22, 95% CI 1.46-3.37). CONCLUSIONS: Poor prognostic factors, such as advanced age, poor performance status, or active extracranial disease, correspond with an increase in physicians' reported preference for using WBRT. When controlling for clinical factors, equipment access was independently associated with choice of SRS. The large variability in preferences suggests that more information about the relative harms and benefits of these options is needed to guide decision-making.

Hospice knowledge and intentions among Latinos using safety-net clinics.

BACKGROUND: Hospice use is low in Latinos but we know little about explanations for this pattern. OBJECTIVE: To describe factors associated with knowledge of and intention to use hospice for cancer care. METHODS: We conducted a Spanish-language, interviewer-administered cross-sectional survey of 331 Latino immigrants from Central and South America in safety-net clinics. Hospice intentions were measured using a hypothetical scenario. We used logistic regression and multiple imputations to test associations between cultural values, social acculturation, and other variables and knowledge and intentions. RESULTS: Only 29% knew about hospice and 35% would choose hospice care (once it was defined). Collectivist (group-focused) views (odds ratio [OR] 1.06 per 1-point increase, 95% confidence interval [CI] 1.01-1.12, p=.05), endorsing family-centric values (OR 1.03 per 1-point increase, 95% CI 1.01-1.04, p=.004), and higher education were associated with greater hospice knowledge after considering covariates. Greater social ties were also independently associated with greater knowledge, but knowledge was not related to hospice intentions. Individuals who believed in maintaining secrecy about prognosis were 19% less likely to choose hospice than those who did not endorse secrecy (OR 0.81, 95% CI 0.67-0.99, p = .038). The most socially acculturated individuals were significantly more likely to choose hospice than those with less acculturation (OR 1.19 for each 1-unit increase, 95% CI 10.6-1.34, p = .004). CONCLUSIONS: Hospice knowledge may be necessary but is not sufficient to increase hospice use among immigrant Latinos. Latino social networks and organizations may provide a natural leverage point for interventions. Interventions to increase hospice use may need to consider culturally related values.

Patient and physician decision styles and breast cancer chemotherapy use in older women: Cancer and Leukemia Group B protocol 369901.

PURPOSE Physician and patient decision styles may influence breast cancer care for patients ≥ 65 years ("older") because there is uncertainty about chemotherapy benefits in this group. We evaluate associations between decision-making styles and actual treatment. METHODS Data were collected from women treated outside of clinical trials for newly diagnosed stage I to III breast cancer (83% response) from January 2004 through April 2011 in 75 cooperative group sites. Physicians completed a one-time mailed survey (91% response), and clinical data were abstracted from charts. Patient decision style was measured on a five-point scale. Oncologists' preference for prescribing chemotherapy was based on standardized vignettes. Regression and multiple imputation were used to assess associations between chemotherapy and other variables. Results There were 1,174 women seen by 212 oncologists; 43% of women received chemotherapy. One-third of women preferred to make their own treatment decision. Patient and physician decision styles were independently associated with chemotherapy. Women who preferred less physician input had lower odds of chemotherapy than women who preferred more input (odds ratio [OR] = 0.79 per 1-point change; 95% CI, 0.65 to 0.97; P = .02) after considering covariates. Patients whose oncologists had a high chemotherapy preference had higher odds of receiving chemotherapy (OR = 2.65; 95% CI, 1.80 to 3.89; P < .001) than those who saw oncologists with a low preference. CONCLUSION Physicians' and older patients' decision styles are each associated with breast cancer chemotherapy use. It will be important to re-evaluate the impact of decision styles when there is greater empirical evidence about the benefits and risks of chemotherapy in older patients.

Use of colony-stimulating factors with chemotherapy: opportunities for cost savings and improved outcomes.

Myeloid colony-stimulating factors (CSFs) decrease the risk of febrile neutropenia (FN) from high-risk chemotherapy regimens administered to patients at 20% or greater risk of FN, but little is known about their use in clinical practice. We evaluated CSF use in a multiregional population-based cohort of lung and colorectal cancer patients (N = 1849). Only 17% (95% confidence interval [CI] = 8% to 26%) patients treated with high-risk chemotherapy regimens received CSFs, compared with 18% (95% CI = 16% to 20%) and 10% (95% CI = 8% to 12%) of patients treated with intermediate- (10%-20% risk of FN) and low-risk (<10% risk of FN) chemotherapy regimens, respectively. Using a generalized estimating equation model, we found that enrollment in a health maintenance organization (HMO) was strongly associated with a lower adjusted odds of discretionary CSF use, compared with non-HMO patients (odds ratio = 0.44, 95% CI = 0.32 to 0.60, P < .001). All statistical tests were two-sided. Overall, 96% (95% CI = 93% to 98%) of CSFs were administered in scenarios where CSF therapy is not recommended by evidence-based guidelines. This finding suggests that policies to decrease CSF use in patients at lower or intermediate risk of FN may yield substantial cost savings without compromising patient outcomes.

Associations of physical activity with quality of life and functional ability in breast cancer patients during active adjuvant treatment: the Pathways Study.

Physical activity can improve quality of life (QOL) in breast cancer survivors but little is known about associations of physical activity and QOL during active cancer therapy. We examine associations between activity levels and QOL in a large cohort of breast cancer patients. Women with invasive, non-metastatic breast cancer (n=2,279) were enrolled between 2006 and 2009 from a managed care organization; assessment were done during active therapy. A physical activity frequency questionnaire was used to calculate the average weekly metabolic equivalent task (MET) hours spent in moderate and vigorous activity during active treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Breast Cancer. Linear regression models tested cross-sectional associations of QOL and functional well-being with physical activity and covariates [socio-demographics, comorbidity, body mass index (BMI), clinical variables, social support, and assessment timing]. Physical activity had a significant positive unadjusted association with all QOL sub-scales (except emotional well-being) (all P values < 0.01). Overall QOL was 4.6 points higher for women in the highest quartile of moderate and vigorous activity versus women in the lowest quartile (P<0.001). In regression models, higher activity was associated with better overall QOL and functional well-being, controlling for covariates (P<0.05). Increasing BMI was also independently but inversely associated with overall QOL (P<0.001) but did not explain the relationship of activity and QOL. White women reported the higher levels of activity than minority women and activity was associated with QOL for Whites but not for minority women. Greater physical activity is associated with small but clinically meaningful increases in QOL during active breast cancer care therapy for Whites but this effect is not seen for minority women. If confirmed in longitudinal analyses, these differences may have implications for disparities research.