The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

OBJECTIVE: Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. DESIGN: Cross-sectional. SETTING: The Center for Health Behavior Research at the University of Maryland School of Public Health. SAMPLE: Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). METHOD: Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. MAIN OUTCOME MEASURES: Metabolite abundances. RESULTS: Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). CONCLUSIONS: The vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. TWEETABLE ABSTRACT: Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.

Cigarette smoking is associated with an altered vaginal tract metabolomic profile.

Cigarette smoking has been associated with both the diagnosis of bacterial vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As the mechanism linking smoking with vaginal microbiota and BV is unclear, we sought to compare the vaginal metabolomes of smokers and non-smokers (17 smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S rRNA gene populations revealed samples clustered into three community state types (CSTs) ---- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST-IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the breakdown metabolites cotinine and hydroxycotinine were substantially higher in smokers, as expected. Among women categorized to CST-IV, biogenic amines, including agmatine, cadaverine, putrescine, tryptamine and tyramine were substantially higher in smokers, while dipeptides were lower in smokers. These biogenic amines are known to affect the virulence of infective pathogens and contribute to vaginal malodor. Our data suggest that cigarette smoking is associated with differences in important vaginal metabolites, and women who smoke, and particularly women who are also depauperate for Lactobacillus spp., may have increased susceptibilities to urogenital infections and increased malodor.

Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation.

A population pharmacokinetic and pharmacodynamic analysis evaluated the relationships of dose, plasma concentrations of bupropion and metabolites, and patient covariates with the safety and efficacy of bupropion sustained release (SR) for smoking cessation. A total of 519 outpatient chronic cigarette smokers were randomized to one of three bupropion SR doses: 100, 150, or 300 mg/day or placebo. The bupropion plasma concentration time data were fit and subject-specific bayesian estimates of clearance were obtained. Logistic regression analyses evaluated the role of dose, concentrations, and covariates in predicting efficacy and safety endpoints. For the evaluation of efficacy, patients were classified as quitters or non-quitters on the basis of a 4-week quit variable (defined as complete abstinence for weeks 4-7 of the study). For the evaluation of safety, patients were classified into two categories for each adverse event evaluated, corresponding to whether the patient ever experienced the adverse event during the course of the study or never experienced the event, regardless of whether the event was treatment-emergent. The efficacy of bupropion SR in facilitating smoking cessation was found to be related to dose and a mean metabolite concentration, and quitting in general was found to be related to the number of cigarettes smoked per day at baseline. Smoking cessation was 1.42, 1.69, and 2.84 times more likely in patients receiving 100, 150, and 300 mg/day of bupropion SR, respectively, as compared to placebo (p = 0.0001). As the baseline number of cigarettes smoked per day increased, the likelihood of quitting decreased regardless of the treatment condition. Insomnia and dry mouth were positively associated with mean metabolite concentrations, and dry mouth was inversely related to patient weight. Anxiety was inversely related to predicted steady-state concentration (Cpss), suggesting a positive effect on this withdrawal symptom. Bupropion SR exhibits a statistically significant dose/plasma level-response relationship for smoking cessation. Dry mouth and insomnia, related to concentrations, may be managed with dose reduction, with the realization that smoking cessation may be impaired.

Bupropion for smoking cessation : predictors of successful outcome.

OBJECTIVES: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers. DESIGN: A double-blind, placebo-controlled, dose-response trial. SETTING: Multicenter (three sites) study conducted in the United States. PARTICIPANTS: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking. INTERVENTION: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up). MEASUREMENTS AND RESULTS: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerström Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021). CONCLUSION: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used.

Pharmacologic treatments for the nicotine dependent smoker.

OBJECTIVE: To explore the biology of nicotine addiction and to investigate the latest pharmacological treatments for nicotine dependence. METHODS: Explore the research literature for treating nicotine dependence. RESULTS: Nicotine is an additive drug and the most effective methods for treating dependence are nicotine replacement therapy (NRT) and bupropion SR. CONCLUSION: The best available treatments for nicotine dependence are pharmacological adjuncts; specifically, NRT and bupropion SR when combined with behavioral counseling.

Treating nicotine dependence.

To explore the biology of nicotine addiction and to discuss the latest effective treatments for nicotine dependence. Research indicates that the most effective methods for treating nicotine dependence are nicotine replacement therapy (NRT) and bupropion SR (BUP). We conclude that pharmacological adjuncts (NRT & BUP) achieve their greatest success when combined with behavioral counseling.

Correlates of youth smokeless tobacco use.

The objectives of this study are to identify knowledge and attitude variables that correlate with smokeless tobacco use and how youth users and non-users differ in their attitudes and knowledge about smokeless tobacco. A randomized cluster sample of 1834 total fifth, eighth, and 11th grade students in West Virginia public schools during the 1996-1997 school year were surveyed on smokeless tobacco knowledge, attitudes and practices. Data from 648 male non-users and 160 male monthly and daily users of smokeless tobacco were compared using chi 2 and two-tailed t-tests. Logistic regression analysis of survey variables revealed the following correlates of smokeless tobacco use: having a family member not living in the home who uses, having a friend who uses, playing football, having tried cigarettes, and having parents who would permit use at home. Important differences exist in knowledge and attitudes regarding smokeless tobacco between users and non-users in fifth, eighth, and 11th grade West Virginia public schools. Correlates of smokeless tobacco use are identified which can be used to target prevention programs.

Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism.

BACKGROUND: A past history of major depression or alcoholism has been associated with poorer smoking treatment outcomes. AIM: To evaluate the efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism, and changes in depressive symptoms during smoking abstinence. METHOD: Data were drawn from a multicentre trial of bupropion for smoking cessation. Smokers (n = 615) received placebo or bupropion sustained-release at 100, 150, or 300 mg/day for six weeks after target quit date (TQD). The primary outcome was the point prevalence smoking abstinence at the end of treatment and at one year. The Beck Depression Inventory (BDI) was used to assess depressive symptoms. RESULTS: A significant dose-response effect of bupropion for smoking cessation was found. This was independent of history of major depression or alcoholism. Among those continuously abstinent from smoking for two weeks following TQD, an increase in BDI score was associated with a return to smoking at end of treatment. CONCLUSIONS: Bupropion is efficacious for smoking cessation independently of a former history of major depression or alcoholism. Increases in depressive symptoms during an initial period of abstinence are associated with a return to smoking.

The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day.

BACKGROUND: This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day. METHODS: A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation. The latter study included group smoking cessation counseling and randomized assignment to 21, 14, or 7 mg nicotine patches or placebo patches. Seven of nine smoking cessation research centers participated in the long term follow-up investigation. RESULTS: The self-reported continuous quit rate among patients originally assigned 21 mg (20.2%) was significantly higher than rates for patients assigned 14 mg (10.4%), 7 mg (11.8%), or placebo patches (7.4%). Log rank survival analysis found no difference in relapse rates after 1 year postcessation. Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age (3 vs 13%, respectively). Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women. Of the 63 continuous abstainers surveyed, 30 respondents (48%) reported that they no longer craved cigarettes, and no individual reported daily craving for cigarettes. CONCLUSIONS: Nicotine patch therapy with 21 mg/day patches resulted in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo. Relapse rates among the various treatment conditions were similar after 1 year postcessation.

A comparison of sustained-release bupropion and placebo for smoking cessation.

BACKGROUND AND METHODS: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. RESULTS: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. CONCLUSIONS: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.

Relationship of alcohol consumption and recreational boating in Beaufort County, North Carolina.

The purpose of this study was to examine the relationship between alcohol use and recreational boating activities. Two hundred eleven (n = 211) boaters were surveyed at three boating access locations in Beaufort County, North Carolina. The survey questionnaire consisted of fifteen questions designed to obtain information on boat operators and their use of alcoholic beverages while engaging in boating activities. Prevalence and amount of alcohol use while boating were significantly associated (p < .05) with the type of activity engaged in. Among those boaters who had received some type of boating safety education, a higher prevalence of alcohol use while boating was observed. The prevalence and amount of alcohol use while boating were found to be significantly (p < .05) associated with the location (public versus private) of boating access. In light of the findings, it is apparent that boating alcohol education and legislation for the North Carolina boating population need assessment and revision. The implications of the findings could have far-reaching effects upon education and prevention among the recreational boating population, particularly if further research in this area supports these finding.

Smokeless tobacco use among American college students.

This study sought to delineate patterns of smokeless tobacco use among college students in the United States. A national sample (N = 5,894) of approximately equal numbers of men and women from 72 colleges and universities participated in the study. Eight percent of the college students in the Northeast used smokeless tobacco, whereas 15% in the South Central United States were using it. Seventeen percent of the American Indian, 14% of Mexican-American, 12% of white, and 4% of black students reported they had dipped or chewed. Smokeless tobacco users were more likely to have family and friends who also used smokeless tobacco. Almost two thirds (63%) of current users plan to continue to dip or chew. More than half (57%) the users consumed less than two cans or pouches per week. Smokeless tobacco is a serious problem in American colleges and universities. Unless prevention and cessation efforts target this group, the problem will continue to increase and ultimately could result in an oral cancer epidemic.

Relapse prevention: implications for health promotion professionals.

Health promotion and education efforts often are designed to promote behavior changes among clients, students, or participants. The primary emphasis of health promotion has been the initial behavior change process, with little attention directed to follow-up or after-care. The relapse prevention model (RP) presents a strategy to enhance the likelihood of maintaining a behavior change using methods clearly rooted in social learning theory. This article provides an overview of the RP model and examples of the implication of RP for health promotion and education programs.

Smokeless tobacco use by youth in the U.S.

Oral snuff and chewing tobacco, commonly referred to as smokeless tobacco, are being used by many adolescent and young adult males, and no indication exists that use by this group is declining. Users are at risk for oral cancer, noncancerous oral pathology such as leukoplakias, and addiction. Information about patterns of smokeless tobacco use and motivations of users may help planners develop and implement interventions. Variables include the importance of peer and family influences, social image, knowledge of harmful effects, regional differences, use of other substances, and addiction. Due to the addictive nature of smokeless tobacco, older youth may need cessation programs. Health educators are encouraged to include smokeless tobacco in their tobacco use prevention programs and to develop and implement comprehensive tobacco interventions appropriate for their youth population.