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Introduction:: In recent years, there has been a proliferation of potential reduced-exposure tobacco products (PREPs) marketed that claim to be less harmful or less addictive, compared with conventional cigarettes. Tobacco control scientists have raised concerns about the potential adverse impact of marketing of these products for smoking prevention and cessation efforts. Although these products have not been widely used among smokers, there are few data available on consumers’ awareness and attitudes toward these products. [ABSTRACT FROM PUBLISHER]

• Combining DSTAT with azacitidine appears feasible with no increased toxicity seen. • A 20 % response rate was observed in this patient population with HMA refractory MDS. • Mobilization of myeloblasts was not observed during the first cycle of DSTAT and azacitidine. Leukemia stem cells utilize cell adhesion molecules like CXCR4/CXCL12 to home to bone marrow stromal niches where they are maintained in a dormant, protected state. Dociparstat sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action, including inhibition of the CXCR4/CXCL12 axis, blocking HMGB1, and binding platelet factor 4 (PF-4). We conducted a pilot study adding DSTAT to azacitidine for patients with AML or MDS unresponsive to or relapsed after prior hypomethylating agent therapy, hypothesizing that DSTAT may improve response rates. Twenty patients were enrolled, with a median of 2 prior lines of therapy and 6 cycles of prior hypomethylating agents. Among fifteen patients evaluable for response, there was 1 complete remission, and 3 marrow complete remissions, for a response rate of 27 % among evaluable patients (20 % overall). Hematologic improvement was observed in 5 additional patients. The median overall survival for all enrolled patients was 205 days (95 % CI 119–302). While cytopenias and infections were common, these were not out of proportion to what would be expected in this population of patients undergoing treatment with azacitidine alone. In summary, this trial demonstrated the feasibility of combining DSTAT with azacitidine, with several responses observed, suggesting this combination warrants further study. [ABSTRACT FROM AUTHOR]

Objectives. Smokeless tobacco has many adverse health effects. We analyzed long-term national trends in smokeless tobacco use. Methods. We used 1987 to 2000 National Health Interview Survey data for adults aged 18 years and older, 1986 to 2003 data from Monitoring the Future surveys of adolescents, and 1991 to 2003 data from the Youth Risk Behavior Survey for 9th- to 12th-grade students to examine overall and demographic-specific trends. Results. Smokeless tobacco use among adult and adolescent females was low and showed little change. Smokeless tobacco use among men declined slowly (relative decline = 26%), with the largest declines among those aged 18 to 24 years or 65 years and older, Blacks, residents of the South, and persons in more rural areas. Overall and demographic-specific data for adolescent boys indicate that smokeless tobacco use increased for 12th-grade students from 1986 until the early 1990s, but has subsequently declined rapidly in all grades since then (range of relative overall declines=43% to 48%). Conclusions. Smokeless tobacco use has declined sharply, especially among adolescent boys. Ongoing prevention and cessation efforts are needed to continue this trend. (Am J Public Health. 2006;96:897-905.) [ABSTRACT FROM AUTHOR]

Study Objective: To study the efficacy of high doses of beta-ser-interferon (recombinant human 17-serine beta-interferon) in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma.Design: A nonrandomized, controlled trial of two high-dose regimens of beta-ser-interferon administered until tumor progression, toxicity, or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection occurred.Setting: An AIDS treatment clinic at a tertiary care center.Patients: A sequential sample of 39 patients with biopsy-proven, AIDS-related Kaposi sarcoma were enrolled during a 2-year period. Thirty-eight patients were evaluable for response. Most patients (35 of 38) had one or more of the following clinical or laboratory predictors for a poor response to interferon therapy: HIV p24 antigenemia, low CD4 cell numbers, elevated beta 2-microglobulin levels, previous opportunistic infections, or previous systemic chemotherapy.Interventions: Beta-ser-interferon was self-administered subcutaneously at home 5 days per week. The first 21 patients used 90 million IU/d, and the remainder used 180 million IU/d.Measurements and Main Results: Six patients (16%) had a major clinical response, and 15 (39%) had stable disease for prolonged periods. Toxicities were minimal; the major toxicity was a skin reaction at the injection site. The HIV p24 antigen level declined more than 50% in 8 of the 19 patients with initial values greater than 50 pg/mL. Antiretroviral activity and antitumor activity were seen only in patients with normal initial beta 2-microglobulin levels. Minimal changes were seen in CD4 and CD8 cell numbers. Only 1 patient had an opportunistic infection while on study, but five other patients developed infections after treatment was discontinued for an incidence of six opportunistic infections in 285 patient-observation months.Conclusions: The high doses of interferon did not improve the major response rate in patients with poor-prognosis, AIDS-related Kaposi sarcoma. There was, however, a suggestion of antiviral activity in patients with normal beta 2-microglobulin levels and a decrease in the expected incidence of opportunistic infections. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This Overview paper (I of V) summarizes research work to date on monitoring the tobacco use epidemic, discusses the recommendations made at the November, 2002 National Tobacco Monitoring, Research and Evaluation Workshop sponsored by the U.S. National Cancer Institute (NCI), Centers for Disease Control and Prevention (CDC), the American Legacy Foundation, and the Robert Wood Johnson Foundation on the topic of tobacco surveillance and evaluation, and discusses the current state of affairs. Methods: A conceptual model based on the classical infectious diseases framework/paradigm focusing on the Agent, Host, Vector and Environment is used to integrate the work presented in the four other papers that appear in this supplemental issue of Preventive Medicine. Results: The Agent paper (II) describes surveillance on tobacco products and biomarkers; the Host paper (III) describes surveillance on the smoker/user, or potential smoker/user; the Vector paper (IV) describes monitoring of industry activity; and the Environment paper (V) describes several key strategies for monitoring influential environmental factors. Overall, some improvements to the nation''s surveillance system have been made in recent years. However, additional steps are needed to optimize measurement of tobacco use and factors influencing use in the United States. Conclusions: Tobacco monitoring efforts play a vital role in combating the epidemic of addiction and disease produced by various tobacco products. The knowledge and experience gained by the tobacco use prevention and control community through this commitment to linkages of data collected in the domains of Vector and Environment, in addition to Agent and Host, could inform monitoring of a wide range of other public health issues as well, including diet and nutrition, physical activity, overweight and obesity, and substance abuse. [Copyright &y& Elsevier]

Purpose: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ., Methods: This open-label, single-arm phase II study treated recurrent TMZ-resistant GBM patients with standard monthly TMZ plus concurrent daily DSF 80 mg PO TID and Cu 1.5 mg PO TID. Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ. Known isocitrate dehydrogenase (IDH) mutant or secondary GBMs were excluded. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit (response or stable disease for at least 6 months), and safety., Results: From March 2017 to January 2018, 23 recurrent TMZ-resistant GBM patients were enrolled across seven centers, and 21 patients were evaluable for response. The median duration of DSF/Cu was 1.6 cycles (range: 0.1-12.0). The ORR was 0%, but 14% had clinical benefit. Median PFS was 1.7 months, and median OS was 7.1 months. Only one patient (4%) had dose-limiting toxicity (grade three elevated alanine transaminase)., Conclusions: Addition of DSF/Cu to TMZ for TMZ-resistant IDH-wild type GBM appears well tolerated but has limited activity for unselected population.

Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low-anticoagulant heparin derivative. In this pilot study, we combined CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56 years; 3 women). Three, 5, and 4 patients had good-, intermediate-, and poor-risk disease, respectively. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had morphologic complete remission after 1 induction (CR1). Eight patients were alive at a median follow-up of 24 months (4 patients in CR1). Three patients received an allogeneic stem cell transplant in CR1. Median disease-free survival was 14.8 months. Median overall survival was not attained at the maximum follow-up time of 29.4 months. No CX-01-associated serious adverse events occurred. Median day to an untransfused platelet count of at least 20 × 10 9 /L was 21. CX-01 is well tolerated when combined with intensive therapy for AML and appears associated with enhanced count recovery and treatment efficacy., (© 2018 by The American Society of Hematology.)

To identify recent studies in the scientific literature that evaluated structured postgraduate public health and biomedical training programs and reported career outcomes among individual trainees, a comprehensive search of several databases was conducted to identify published studies in English between January 1995 and January 2012. Studies of interest included those that evaluated career outcomes for trainees completing full-time public health or biomedical training programs of at least 12 months duration, with structured training offered on-site. Of the over 600 articles identified, only 13 met the inclusion criteria. Six studies evaluated US federal agency programs and six were of university-based programs. Seven programs were solely or predominantly of physicians, with only one consisting mainly of PhDs. Most studies used a cohort or cross-sectional design. The studies were mainly descriptive, with only four containing statistical data. Type of employment was the most common outcome measure (n = 12) and number of scientific publications (n = 6) was second. The lack of outcomes evaluation data from postgraduate public health and biomedical training programs in the published literature is a lost opportunity for understanding the career paths of trainees and the potential impact of training programs. Suggestions for increasing interest in conducting and reporting evaluation studies of these structured postgraduate training programs are provided.

This study examined associations between cigarette smoking, cancer, and self-reported physical (SF-36 Physical Component Summary Score, [PCS]) and mental health (SF-36 Mental Component Summary Score, [MCS]) among 123,567 Medicare beneficiaries enrolled in managed care plans. As expected for a sample of older individuals, the SF-36 PCS mean (42.6) was lower than the U.S. general population mean of 50. The SF-36 MCS mean (51.7) for the sample was higher than the general population mean. In addition, least squares means revealed significantly poorer health for current smokers and those who recently quit, regardless of their cancer status. Although statistically significant, the differences between current smokers and never smokers were small among those with or without cancer. Encouraging smokers to quit and providing abstinence support to persons who have recently quit may help reduce health-related impacts of cigarette use.

Despite negative financial conditions in recent years, several states were able to successfully maintain funding for tobacco prevention and control, which provided an opportunity to understand the factors associated with success. One explanation may be the level of long-term program sustainability in some states. According to a model developed by Saint Louis University researchers, the five elements critical to tobacco control sustainability are state political and financial climate; community awareness and capacity; program structure and administration; funding stability and planning; and surveillance and evaluation. Five states (Nebraska, New York, Indiana, Virginia, and Colorado) maintained funding for their tobacco control programs. Four of these states gained additional legislative appropriations or prevented a massive reduction; Colorado used a statewide ballot initiative to increase funding. On the basis of the sustainability framework, case studies, and prior research, the major lessons learned for maintaining funding were the importance of (1) strong and experienced leadership, (2) broad and deep organizational and community ties, (3) coordinated efforts, (4) strategic use of surveillance and evaluation data, (5) active dissemination of information about program successes, and (6) policy maker champions. The sustainability framework and lessons learned may provide valuable insights for other public health programs facing funding threats.

Objectives: We examined the pathways to smoking cessation between late adolescence and young adulthood., Methods: We obtained data from a sample of urban African American and Puerto Rican young adults (N=242), mean age 19 years, who reported tobacco use and determined cessation rates between late adolescence and young adulthood. We used structural equation modeling to examine the pathways of positive family relations, family smoking, maladaptive personality attributes, and substance use to smoking cessation., Results: A mediational pathway linked the absence of positive family relations with maladaptive personality attributes, both of which were related to substance use and ultimately smoking cessation. Substance use mediated the path between family smoking and smoking cessation., Conclusions: The results suggest that a positive relationship with one's parents, less smoking in the family, conventional personality attributes, and little or no other substance use facilitate smoking cessation among young adults.

The existence of "hardcore" smokers, those most likely to have substantial difficulty quitting, may have far reaching impact on how to best allocate cessation resources. It has been suggested that hardcore smokers make up only a small fraction of current smokers and therefore do not represent a significant public health problem. However, little is known about the prevalence and nature of this subgroup of smokers in the United States. Based on a national sample, the 1998-1999 Tobacco Use Supplement to the Current Population Survey, we categorized, based on smoking pattern, groups of current smokers who were over age 25 years (N=33,568). We compared hardcore smokers with other groups of current smokers on demographic, environmental, and smoking variables to assess whether hardcore smokers represent a unique group. Hardcore smokers were defined as established daily smokers, consuming 15 or more cigarettes per day with no reported history of quit attempts. Hardcore smokers represent 13.7% of all current smokers and 17.6% of all established smokers. They are more likely to be male, unmarried, not in the work force, and have lower education. They also are more likely to have started smoking at a younger age, smoke more, and are less likely to report contact with smoking restrictions. This analysis suggests that hardcore smokers are distinct from other groups of smokers. These results also indicate that hardcore smokers account for a substantial proportion of smokers and as such may represent a significant public health challenge that needs to be addressed.