Association of Health-Care System With Prostate Cancer-Specific Mortality in African American and Non-Hispanic White Men.

BACKGROUND: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology, and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA). METHODS: We identified African American and White patients diagnosed with prostate cancer between 2004 and 2015 in SEER (n = 311 691) and the VHA (n = 90 749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors. RESULTS: The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17 to 1.30) but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98 to 1.17). African American vs White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10 to 1.60) but not in the VHA (SHR = 1.00, 95% CI = 0.93 to 1.08). Adjusting for disease extent, prostate-specific antigen, and Gleason score eliminated the association between race and PCSM in SEER (aSHR = 1.04, 95% CI = 0.93 to 1.16). CONCLUSIONS: Racial disparities in PCSM were present in a nationally representative registry but not in an equal-access health-care system, because of differences in advanced disease at presentation. Strategies to increase health-care access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes.

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma.

BACKGROUND: Although treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma. METHODS: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan-Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models. RESULTS: The analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity-score matched cohort (n = 195; hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75). CONCLUSION: Compared to current standard of care therapy, inclusion of immunotherapy as first-line therapy was not associated with improved survival in SNM.

Intensive Induction Therapy Compared With CHOP for Hepatosplenic T-cell Lymphoma.

INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL) is a rare peripheral T-cell lymphoma that disproportionately affects individuals with a clinical history of immunosuppression. It carries a poor prognosis, and, owing to its rarity, there is no single or well-established treatment. PATIENTS AND METHODS: We conducted the largest-to-date individual-level meta-analysis based on literature searches to determine the best induction therapy for HSTCL. We compared response rates and survival among patients who received "non-CHOP-based" induction with regimens containing cytarabine, etoposide, and/or platinum-based treatment to those receiving treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapy. We also review additional regimens including alemtuzumab and pentostatin, and assessed the role of consolidation with hematopoietic stem-cell transplantation (HSCT). RESULTS: We identified 166 patients with HSTCL, 118 of whom had sufficient information on induction treatment and survival. Eighty-four patients received non-CHOP-based (N = 34) or CHOP/CHOP-like (N = 50) induction treatment. Non-CHOP-based induction was associated with a complete/partial response rate of 82% compared with 52% (P = .006) with CHOP/CHOP-like and increased median overall survival (P = .00014). Our data showed that maximum survival among patients with HSTCL was achieved with non-CHOP-based induction followed by consolidation with HSCT. CONCLUSIONS: Non-CHOP-based induction appears superior to CHOP/CHOP-like induction in both achieving complete/partial response and durable survival. Induction therapy of HSTCL should be intensified with non-CHOP-based regimens and followed by consolidation with HSCT in eligible patients.

Disparities in knowledge and use of tobacco treatment among smokers in California following healthcare reform.

The Affordable Care Act (ACA) promised to narrow smoking disparities by expanding access to healthcare and mandating comprehensive coverage for tobacco treatment starting in 2014. We examined whether two years after ACA implementation disparities in receiving clinician advice to quit and smokers' knowledge and use of treatment resources remained. We conducted telephone interviews in 2016 with a stratified random sample of self-reported smokers newly enrolled in the Kaiser Permanente Northern California's (KPNC) integrated healthcare delivery system in 2014 (N = 491; 50% female; 53% non-white; 6% Spanish language). We used Poisson regression with robust standard errors to test whether sociodemographics, insurance type, comorbidities, smoking status in 2016 (former, light/nondaily [<5 cigarettes per day], daily), and preferred language (English or Spanish) were associated with receiving clinician advice to quit and knowledge and use of tobacco treatment. We included an interaction between smoking status and language to test whether the relation between smoking status and key outcomes varied with preferred language. Overall, 80% of respondents received clinician advice to quit, 84% knew that KPNC offers cessation counseling, 54% knew that cessation pharmacotherapy is free, 54% used pharmacotherapy, and 6% used counseling. In multivariate models, Spanish-speaking light/nondaily smokers had significantly lower rates of all outcomes, while there was no association with other demographic and clinical characteristics. Following ACA implementation, most smokers newly enrolled in KPNC received clinician advice to quit and over half used pharmacotherapy, yet counseling utilization was low. Spanish-language outreach efforts and treatment services are recommended, particularly for adults who are light/nondaily smokers.

Evaluating the Impact of Eliminating Copayments for Tobacco Cessation Pharmacotherapy.

OBJECTIVES: We examined the impact of the Affordable Care Act-mandated elimination of tobacco cessation pharmacotherapy (TCP) copayments on patient use of TCP, overall and by income. METHODS: Electronic health record data captured any and combination (eg, nicotine gum plus patch) TCP use among adult smokers newly enrolled in Kaiser Permanente Northern California (KPNC). KPNC eliminated TCP copayments in 2015. We included current smokers newly enrolled in the first 6 months of 2014 (before copayment elimination, N=16,199) or 2015 (after elimination, N=16,469). Multivariable models estimated 1-year changes in rates of any TCP fill, and of combination TCP fill, and tested for differences by income (<$50k, $50≥75k, ≥$75k). Through telephone surveys in 2016 with a subset of smokers newly enrolled in 2014 (n=306), we assessed barriers to TCP use, with results stratified by income. RESULTS: Smokers enrolled in KPNC in 2015 versus 2014 were more likely to have a TCP fill (9.1% vs. 8.2%; relative risk, 1.19; 95% confidence interval, 1.11-1.27), and combination TCP fill, among those with any fill (42.3% vs. 37.9%; relative risk, 1.12; 95% confidence interval, 1.02-1.23); findings were stronger for low-income smokers. Low-income patients (<$50k) were less likely to report that clinicians discussed smoking treatments with them (58%) compared with higher income smokers ($50≥75k, 67%; ≥$75k, 83%), and were less aware that TCP was free (40% vs. 53% and 69%, respectively, P-values<0.05). CONCLUSIONS: The Affordable Care Act's copayment elimination was associated with a modest increase in TCP use and a greater effect among low-income smokers. Uptake may have been enhanced if promoted to patients directly and via providers.

Changes in Psychiatric and Medical Conditions and Health Care Utilization Following a Diagnosis of Sexual Assault: A Retrospective Cohort Study.

INTRODUCTION: Sexual assault (SA) is alarmingly common and is associated with higher prevalence of psychiatric and medical conditions. However, many prior studies are limited to cross-sectional designs. Health care systems with electronic health records provide unique longitudinal data to examine whether SA is associated with changes in health and health care utilization. METHODS: The sample included 1350 Kaiser Permanente Northern California adult female patients with a SA diagnosis from 2009 to 2015 and 4050 adult female patients without a SA diagnosis, matched on age, medical facility, and continuous enrollment during the study period. Using a retrospective cohort design, we tested whether a SA diagnosis was associated with 12-month changes in psychiatric and medical comorbidities and health care utilization using difference-in-difference models. Analyses were conducted in 2017. RESULTS: Patients with a SA diagnosis had a higher prevalence of psychiatric and medical comorbidities and greater health care utilization than matched patients without SA in the 12 months before the SA diagnosis, and greater increases in the prevalence of psychiatric disorders and stress-related somatic conditions, and psychiatry and obstetrics/gynecology utilization (all P<0.001), 12 months after the SA diagnosis, relative to matched non-SA patients during this time. DISCUSSION: SA is associated with increases in psychiatric disorders and stress-related somatic conditions as well as increases in utilization of psychiatry and obstetrics/gynecology. Clinicians should be trained in how to inquire about, respond to, and refer women who have experienced SA.

Documentation of e-cigarette use and associations with smoking from 2012 to 2015 in an integrated healthcare delivery system.

It is unclear whether use of electronic nicotine delivery systems (ENDS) precedes cigarette smoking initiation, relapse, and/or quitting. Healthcare systems with electronic health records (EHRs) provide unique data to examine ENDS use and changes in smoking. We examined the incidence of ENDS use (2012-2015) based on clinician documentation and tested whether EHR documented ENDS use is associated with twelve-month changes in patient smoking status using a matched retrospective cohort design. The sample was Kaiser Permanente Northern California (KPNC) patients aged ≥12 with documented ENDS use (N = 7926); 57% were current smokers, 35% former smokers, and 8% never-smokers. ENDS documentation incidence peaked in 2014 for current and former smokers and in 2015 for never-smokers. We matched patients with documented ENDS use to KPNC patients without documented ENDS use (N = 7926) on age, sex, race/ethnicity, and smoking status. Documented ENDS use predicted the likelihood of smoking in the following year. Among current smokers, ENDS use was associated with greater odds of quitting smoking (OR = 1.17, 95%CI = 1.05-1.31). Among former smokers, ENDS use was associated with greater odds of smoking relapse (OR = 1.53, 95%CI = 1.22-1.92). Among never-smokers, ENDS use was associated with greater odds of initiating smoking (OR = 7.41, 95%CI = 3.14-17.5). The overall number of current smokers at 12 months was slightly higher among patients with (N = 3931) versus without (N = 3850) documented ENDS use. Results support both potential harm reduction of ENDS use (quitting combustibles among current smokers) and potential for harm (relapse to combustibles among former smokers, initiation for never-smokers).

Do you vape? Leveraging electronic health records to assess clinician documentation of electronic nicotine delivery system use among adolescents and adults.

Use of electronic nicotine delivery systems (ENDS) has increased substantially over the past decade. However, unlike smoking, which is systematically captured by clinicians through routine screening and discrete documentation fields in the electronic health record (EHR), unknown is the extent to which clinicians are documenting patients' use of ENDS. Data were gathered from medical visits with patients aged 12 and older (N=9,119; 55% male) treated in a large, integrated healthcare system. We used natural language processing to assess the incidence rates of clinician documentation of patients' ENDS use in unstructured tobacco comments in the EHR, and the words most frequently documented in relation to ENDS, from 2006-2015. ENDS documentation in the EHR increased dramatically over time (from 0.01 to 9.5 per 10,000 patients, p<0.0001), particularly among adults aged 18-24 and 25-44. Most prevalent were "e-cig," "electronic cigarettes", and "vape," with much variation in spelling and phrasing of these words. Records of adolescent and young adult patients were more likely to contain the word "vape", and less likely to have "e-cig" and "electronic cigarette" than records of adults (ps<0.0001). The relatively low observed number of patients with ENDS terms in the EHR suggested vast under documentation. While healthcare providers are increasingly documenting patients' use of ENDS in the EHR, overall documentation rates remain low. Discrete EHR fields for standard screening and documentation of ENDS that reflect the language used by patients would provide more complete longitudinal population-level surveillance of ENDS use and its association with short- and long-term health outcomes.

Association of the Affordable Care Act With Smoking and Tobacco Treatment Utilization Among Adults Newly Enrolled in Health Care.

OBJECTIVES: To examine rates of smoking and tobacco treatment utilization by insurance coverage status (Medicaid, commercial, exchange) among newly enrolled patients in the post Affordable Care Act (ACA) era. METHODS: We examined new members who enrolled in Kaiser Permanente Northern California through Medicaid, the California exchange, or nonexchange commercial plans (N=122,298) in the first 6 months of 2014 following ACA implementation. We compared these groups on smoking prevalence and tested whether smokers in each group differed on sociodemographic characteristics and in their utilization of tobacco treatment (pharmacotherapy and counseling) in 2014. RESULTS: Smoking prevalence was higher among Medicaid (22%) than exchange (13%) or commercial (12%) patients (P<0.0001). Controlling for key sociodemographic and clinical characteristics, Medicaid (odds ratio, 1.49; 95% confidence interval, 1.29-1.73) smokers had greater odds of tobacco treatment use than commercial smokers. Other groups at risk for underuse included men, younger patients, Asians, and Latinos. CONCLUSIONS: In this cohort of newly enrolled patients after ACA implementation, Medicaid patients were more likely to be smokers compared with exchange and commercial patients, but they were also more likely to use tobacco treatment. Low tobacco treatment use among exchange and commercial plan smokers, as well as younger men, Asians and Latinos poses a significant obstacle to improving public health and additional targeted outreach strategies may be needed to engage these patients with available health services.

Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients.

BACKGROUND: Apolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients. METHODS: We conducted a population-based case-control study nested in a population of 11,251 women aged 35-69 years at diagnosis with Stage I-III breast cancer between 1985 and 2001 on Denmark's Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers cases among women with ER+ disease treated with tamoxifen for at least 1 year and 300 cases in women with ER- disease never treated with tamoxifen. We matched one control subject per case and assessed ApoD expression in the tumor cell nucleus and cytoplasm using tissue microarray immunohistochemistry. We computed the odds ratio (OR) associating ApoD expression with recurrence and adjusted for potential confounding using logistic regression. RESULTS: Cytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER- tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER- tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null. CONCLUSION: ApoD expression is likely not a predictor of recurrence in tamoxifen-treated patients. IMPACT: This study eliminates the previously suggested marker ApoD as a predictor of recurrence among tamoxifen-treated women.

Smoking Status and Opioid-related Problems and Concerns Among Men and Women on Chronic Opioid Therapy.

OBJECTIVES: Smokers on chronic opioid therapy (COT) for noncancer pain use prescription opioids at higher dosages and are at increased risk for opioid misuse and dependence relative to nonsmokers. The current study aims to assess whether smoking is associated with problems and concerns with COT from the perspective of the patient. MATERIALS AND METHODS: In a large sample (N=972) of adult patients prescribed opioids for chronic noncancer pain, we examined sex-specific associations between smoking status and patient perceptions of problems and concerns with COT using regression analyses, adjusting for covariates. RESULTS: The sample self-identified as 27% current smokers, 44% former smokers, and 29% never smokers. Current smoking (vs. never smoking) was associated with increased odds of an opioid use disorder among males and females, and higher daily opioid dose among males only. Current and former smokers reported significantly fewer problems with opioids relative to never smokers, and this was driven primarily by lower endorsement of problems that are affected by the stimulant properties of nicotine (eg, difficulties thinking clearly, felt less alert or sleepy). DISCUSSION: This study contributes to an understanding of perceived problems and concerns with COT among current, former, and never smokers with chronic noncancer pain. Results suggest that current and former smokers may be a difficult population to target to decrease COT, given that they perceive fewer problems with prescription opioid use, despite higher odds of having an opioid use disorder (males and females) and greater opioid doses (males only).

Two castes sizes of leafcutter ants in task partitioning in foraging activity / Participação de dois tamanhos de castas de operárias de formigas cortadeiras no particionamento de tarefas da atividade de forrageamento

ABSTRACT: Task partitioning in eusocial animals is most likely an evolutionary adaptation that optimizes the efficiency of the colony to grow and reproduce. It was investigated indirect task partitioning in two castes sizes; this involves task partitioning in which the material transported is not transferred directly from one individual to another, but where it is dropped by one ant to be picked up by another. In two separate approaches, it was confirmed previous results pertaining to leaf caching activities among Atta colombica with task partitioning activities involving leaf dropping among Atta sexdens rubropilosa , in which there is a correlation between the size of an individual ant and the leaf fragment it transports. It was also suggested that this correlation exists only in individual ants that cut and transport (CaT) the same fragment to the nest. When task partitioning occurs and individual ants transporting (T) leaf fragments cut by other ants, the correlation becomes looser or disappears. We also observed that CaT ants are smaller than T ants.

RESUMO: Particionamento de tarefas em animais eusociais é provavelmente uma adaptação evolutiva, que otimiza a eficiência de forrageio da colônia, gerando maior capacidade de crescimento e reprodução. Nós investigamos o particionamento indireto de tarefas, com o envolvimento de castas de dois tamanhos distintos. Assim, o material coletado por uma formiga não era transportado diretamente ao ninho, nem transferido diretamente de um indivíduo para outro, mas sim descartado por uma formiga e coletado por outra. Em duas abordagens distintas, nós confirmamos em Atta sexdens rubropilosa resultados anteriores relativos à ocorrência deste particionamento indireto de tarefas, observado em Atta colombica . Mostramos também que, assim como em Atta colombica , há uma correlação entre os tamanhos da formiga e do fragmento de folha transportado quando esta corta e transporta este fragmento ao ninho (CaT). Mais ainda, confirmamos em Atta sexdens que, quando o particionamento de tarefas ocorre e as formigas apenas transportam o fragmento de folhas (T) cortadas por outras formigas, a correlação desaparece. Nós também descrevemos que as formigas CaT são menores do que as T.

X chromosome-wide analysis identifies DNA methylation sites influenced by cigarette smoking.

BACKGROUND: Tobacco smoking is a major cause of chronic disease worldwide. Smoking may induce cellular and molecular changes including epigenetic modification, with both short-term and long-term modification patterns that may contribute to phenotypic expression of diseases. Recent epigenome-wide association studies (EWAS) have identified dozens of smoking-related DNA methylation (DNAm) sites. However, the X chromosomal DNAm sites have been largely overlooked due to a lack of an analytical framework for dealing with the sex-dimorphic distribution. To identify novel smoking-related DNAm sites on the X chromosome, we examined the modality of each X chromosomal DNAm site and conducted a sex-specific association study of cigarette smoking. RESULTS: We used a discovery sample of 139 middle-age twins, and three replication samples of 78 twins, 464 and 333 unrelated individuals including 47, 17, 22, and 89 current smokers, respectively. After correction for multiple testing, the top smoking-related DNAm sites in BCOR and TSC22D3 were significantly hypermethylated and hypomethylated, respectively, among current smokers. These smoking-associated sites were replicated with meta-analysis p-values of 9.17 × 10(-12) and 1.61 × 10(-9). For both sites, the smoking effects on methylation levels were larger in males than that in females. CONCLUSIONS: Our findings highlight the importance of investigating X chromosome methylation patterns and their associations with environmental exposures and disease phenotypes and demonstrate a robust statistical methodology for such study. Existing EWAS of human diseases should incorporate the X chromosomal sites to complete a comprehensive epigenome-wide scan.