Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake.

High salt intake (HS) is a risk factor for cardiovascular and kidney disease. Indeed, HS may promote blood-pressure-independent tissue injury via inflammatory factors. The lipid-lowering 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors exert beneficial lipid-independent effects, reducing the expression and synthesis of inflammatory factors. We hypothesized that HS impairs kidney structure and function in the absence of hypertension, and these changes are reversed by atorvastatin. Four groups of rats were treated for 6 wk in metabolic cages with their diets: normal salt (NS); HS, NS plus atorvastatin and HS plus atorvastatin. We measured basal and final body weight, urinary sodium and protein excretion (U(Prot)V), and systolic blood pressure (SBP). At the end of the experimental period, cholesterolemia, creatinine clearance, renal vascular reactivity, glomerular volume, cortical and glomerular endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-ß1 expression were measured. We found no differences in SBP, body weight, and cholesterolemia. HS rats had increased creatinine clearence, U(Prot)V, and glomerular volume at the end of the study. Acetylcholine-induced vasodilatation decreased by 40.4% in HS rats (P < 0.05). HS decreased cortical and glomerular eNOS and caused mild glomerular sclerosis, interstitial mononuclear cell infiltration, and increased cortical expression of TGF-ß1. All of these salt-induced changes were reversed by atorvastatin. We conclude that long-term HS induces inflammatory and hemodynamic changes in the kidney that are independent of SBP. Atorvastatin corrected all, suggesting that the nitric oxide-oxidative stress balance plays a significant role in the earlier stages of salt induced kidney damage.

Under-use of tobacco dependence treatment among Wisconsin's fee-for-service Medicaid recipients.

BACKGROUND: Wisconsin Medicaid enrollees are eligible for treatment for tobacco dependence at minimal charge to the enrollee. This paper describes an evaluation of the use of this treatment within the Wisconsin fee-for-service Medicaid program. METHODS: Pharmaceutical claims data for Medicaid fee-for-service patients were analyzed for the year 1999 to determine rates of treatment use. RESULTS: Of 261,435 adults enrolled in fee-for-service Medicaid for 1 or more months, only 1131 adults received pharmacotherapy for tobacco dependence in 1999 at a modest cost of approximately $135 per treatment user. This represents less than 2% of the adult Medicaid fee-for-service patients who smoke. DISCUSSION: Few Medicaid fee-for-service enrollees are receiving evidence-based treatment for tobacco dependence, the leading preventable cause of illness and death in Wisconsin. The 16,000 Wisconsin physicians caring for these patients are urged to intervene with every Medicaid patient who smokes. To assist in this effort, the Wisconsin Medicaid program's coverage for tobacco dependence treatment is explained and a series of myths are corrected.

Strike while the iron is hot: can stepped-care treatments resurrect relapsing smokers?

The efficacies of 2 group counseling step-up treatments for smoking cessation, cognitive-behavioral/skill training therapy (CBT) and motivational interviewing/supportive (MIS) therapy, were compared with brief intervention (BI) treatment in a sample of 677 smokers. Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse (no smoking vs. any smoking during the first postquit week. respectively). All participants received 8 weeks of nicotine patch therapy. BI consisted of 3 brief individual cessation counseling sessions; CBT and MIS participants received BI treatment and 6 group counseling sessions. Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI. Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT. Other hypotheses were not supported.

Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment. METHODS: This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study. RESULTS: The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo). CONCLUSION: Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.

Gender and racial/ethnic differences in tobacco-dependence treatment: a commentary and research recommendations.

The preparation of the Public Health Service Report, Treating Tobacco Use and Dependence, brought to light a substantial gap in the smoking cessation literature; there is little or no research evidence regarding the success of formal tobacco-dependence treatment specific to gender or racial/ethnic status. Of the 192 articles included in the meta-analyses of the evidence-based PHS Report, none included results based on racial/ethnic group and only four reported results by gender. This commentary identifies tobacco use as a problem that crosses gender and racial/ethnic boundaries, reviews reasons that the different genders or racial/ethnic groups might require different tobacco-dependence treatments, provides suggestive evidence that both gender and racial/ethnic status influence tobacco-dependence treatment efficacy, and recommends changes and directions for future clinical research that will address gender and racial/ethnicity effects.

US public health service clinical practice guideline: treating tobacco use and dependence.

Treating Tobacco Use and Dependence, a Public Health Service-sponsored Clinical Practice Guideline, is a product of the Tobacco Use and Dependence Guideline Panel ("the panel"), consortium representatives, consultants, and staff. These 30 individuals were charged with the responsibility of identifying effective, experimentally validated tobacco dependence treatments and practices. The updated guideline was sponsored by a consortium of seven Federal Government and nonprofit organizations: the Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, Robert Wood Johnson Foundation, and University of Wisconsin Medical School's Center for Tobacco Research and Intervention. This guideline is an updated version of the 1996 Smoking Cessation Clinical Practice Guideline No. 18 that was sponsored by the Agency for Health Care Policy and Research (now the AHRQ), United States Department of Health and Human Services. The original guideline reflected the extant scientific research literature published between 1975 and 1994. The updated guideline was written because new, effective clinical treatments for tobacco dependence have been identified since 1994. The accelerating pace of tobacco research that prompted the update is reflected in the fact that 3,000 articles on tobacco were identified as published between 1975 and 1994, contributing to the original guideline. Another 3,000 were published between 1995 and 1999 and contributed to the updated guideline. These 6,000 articles were screened and reviewed to identify a much smaller group of articles that served as the basis for guideline data analyses and panel opinion. This guideline contains strategies and recommendations designed to assist clinicians, tobacco dependence treatment specialists, and health care administrators, insurers, and purchasers in delivering and supporting effective treatments for tobacco use and dependence. The recommendations were made as a result of a systematic review and analysis of the extant scientific literature, using meta-analysis as the primary analytic technique. The strength of evidence that served as the basis for each recommendation is clearly indicated in the guideline. A draft of the guideline was peer-reviewed prior to publication, and the comments of 70 external reviewers were incorporated into the final document. The key recommendations of the updated guideline, Treating Tobacco Use and Dependence, based on the literature review and expert panel opinion, are as follows: 1. Tobacco dependence is a chronic condition that often requires repeated intervention. However, effective treatments exist that can produce long-term or even permanent abstinence. 2. Because effective tobacco dependence treatments are available, every patient who uses tobacco should be offered at least one of these treatments: Patients willing to try to quit tobacco use should be provided with treatments identified as effective in this guideline. Patients unwilling to try to quit tobacco use should be provided with a brief intervention designed to increase their motivation to quit. 3. It is essential that clinicians and health care delivery systems (including administrators, insurers, and purchasers) institutionalize the consistent identification, documentation, and treatment of every tobacco user seen in a health care setting. 4. Brief tobacco dependence treatment is effective, and every patient who uses tobacco should be offered at least brief treatment. 5. There is a strong dose-response relation between the intensity of tobacco dependence counseling and its effectiveness. Treatments involving person-to-person contact (via individual, group, or proactive telephone counseling) are consistently effective, and their effectiveness increases with treatment intensity (eg, minutes of contact). 6. (ABSTRACT TRUNCATED)

Helping Wisconsin women quit smoking: a successful collaboration.

The cost of treatments for tobacco dependence frequently presents a financial barrier to their use. To overcome such barriers, the Wisconsin Women's Health Foundation, the Wisconsin Bureau of Public Health, the McNeil Consumer Healthcare, and the University of Wisconsin Center for Tobacco Research and Intervention collaborated in an initiative to distribute nicotine patches to Wisconsin women at no cost. As a result of this collaborative effort, approximately 19,000 women received a 6-week course of Nicotrol Patches. To evaluate the effectiveness of this initiative, a sample of 500 recipients were contacted and surveyed by telephone 6 months after receiving their patches. Approximately 22% of these women reported total abstinence at 6 months, and another 77% reported they had reduced their smoking. At follow-up, women who had successfully quit rated their health status significantly better than women who were still smoking. More than 99% of respondents recommended that the program be repeated. Extrapolating the observed abstinence rate to the 19,000 patch recipients, an estimated 4000 Wisconsin women successfully quit smoking as a result of this program.

Smoking withdrawal dynamics in unaided quitters.

Considerable research shows that withdrawal severity is inconsistently related to smoking cessation outcomes. This may result from measurement problems or failure to scrutinize important dimensions of the withdrawal experience. Two recent studies demonstrated that withdrawal elevation and variations in the time course of withdrawal were related to relapse in smokers treated with the nicotine patch (T. M. Piasecki, M. C. Fiore, & T. B. Baker, 1998). This article reports a conceptual replication and extension of those findings in unaided quitters. Evidence for temporal heterogeneity was found across different types of withdrawal symptoms. Patterns or slopes of affect and urge reports over time predicted smoking status at follow-up, as did mean elevation in withdrawal symptoms. These results suggest that affect and urge withdrawal symptoms make independent contributions to relapse and that relapse is related to both symptom severity and trajectory.

Cost-benefit analysis of sustained-release bupropion, nicotine patch, or both for smoking cessation.

BACKGROUND: The nicotine transdermal patch (NTP) has been shown previously to be a cost-effective smoking cessation intervention. This is the first economic analysis comparing the NTP with the only non-nicotine-containing pharmacological intervention, bupropion HCl. METHODS: Decision-tree analysis, based on a previously published cost-benefit smoking-cessation model, was used to determine the optimal treatment from the standpoint of costs versus benefits, from the employer's perspective. Base-case probabilities of successful quitting in our model came from clinical trial point-prevalence data at the end of a 1-year follow-up study (N = 893) comparing placebo, bupropion, NTP, and bupropion/NTP in combination, administered along with minimal counseling. Sensitivity analyses were performed to determine the effects of variations in base-case assumptions regarding the monetary benefits that would accrue if an intervention were successful, probabilities of quitting, drug costs, cost of lost work time for a health care provider visit, and cost of the visit itself. RESULTS: The analysis showed that bupropion is more cost-beneficial than either NTP or bupropion/NTP, with a net benefit in the first post-quit year of up to $338 per employee who attempts to quit compared with $26 for NTP, $178 for the two in combination, and $258 for placebo. These results were robust to most plausible variations in the assumptions used in the model. One exception was the monetary benefit of successful intervention (assumed in the base-case to be $1,654). If this benefit were actually less than $1, 112, placebo (i.e., minimal counseling with no pharmacological intervention) would be more cost-beneficial than any of the active treatments. CONCLUSION: From an employer's perspective, bupropion 300 mg/day for 9 weeks is a more cost-beneficial smoking cessation intervention than the nicotine patch, and under most scenarios, bupropion is also more cost-beneficial than placebo.

Development and validation of the Wisconsin Smoking Withdrawal Scale.

The accurate assessment of nicotine withdrawal is important theoretically and clinically. A 28-item scale, the Wisconsin Smoking Withdrawal Scale, was developed that contains 7 reliable subscales tapping the major symptom elements of the nicotine withdrawal syndrome. Coefficients alpha for the subscales range from .75 to .93. This scale is sensitive to smoking withdrawal, is predictive of smoking cessation outcomes, and yields data that conform to a 7-factor structure. The 7 scales predicted intratreatment smoking, chi2(7, N = 163) = 15.19, p = .034. Moreover, the questionnaire is sufficiently brief so that it can be used in both clinical and research contexts.

Gender differences in smoking cessation.

Gender differences in smoking quit rates are frequently reported and are the subject of much speculation. This study examined the generalizability of gender differences in abstinence across study sites, treatments, and time of relapse, as well as potential mediators and moderators of gender effects. Participants were smokers who participated in 3 randomized clinical trials of the nicotine patch (N = 632). Men had higher cessation rates than women at all follow-ups. The impact of gender on abstinence was unaffected by controlling for study site, treatment, or time of relapse. There was little evidence for mediation or moderation of this relation by any of a host of predictor variables. The magnitude and consistency of the gender differential, coupled with an inability to account for it, highlights a compelling need for additional research specifically aimed at elucidating the relation between gender and abstinence.

The epidemiology of tobacco use, dependence, and cessation in the United States.

Tobacco use, primarily in the form of cigarette smoking, is the leading preventable cause of death in the United States. After epidemic increases in current smoking in the first half of the 20th century, overall rates of smoking have decreased during the past 30 years. Certain sociodemographic groups continue to have high rates of tobacco use. The prevalence of current smoking in adults in the United States decreased from 42.4% in 1965 to 24.7% in 1995. Recent epidemiologic data indicate that 47 million adults currently smoke cigarettes and over 5 million use smokeless tobacco; over 3 million adolescents are current smokers and over 750,000 use smokeless tobacco. Thus, tobacco use continues to be a major public health concern.

The Agency for Health Care Policy and Research smoking cessation clinical practice guideline: basics and beyond.

The 1996 Agency for Health Care Policy and Research's Smoking Cessation Clinical Practice Guideline provides a strong empirical foundation for effective smoking cessation interventions in primary care. Screening all patients for tobacco use status at each clinic visit and providing at least brief cessation advice to all smokers can have a significant system-wide effect. Adding additional treatment components, such as pharmacotherapy, problem solving, and social support, can increase quit rates by twofold or more. Information on effective and ineffective treatment components is provided, along with new information published after the release of the Guideline.

Manipulating smoking motivation: impact on an electrophysiological index of approach motivation.

A chief goal of this research was to determine whether stimuli and events known to enhance smoking motivation also influence a physiological variable with the potential to index approach motivation. Asymmetry of electroencephalographic (EEG) activity across the frontal regions of the 2 hemispheres (left minus right hemisphere activation) was used to index approach motivation. In theory, if EEG asymmetry sensitively indexes approach dispositions, it should be influenced by manipulations known to affect smoking motivation, that is, exposure to smoking cues and tobacco deprivation. Seventy-two smokers participated in this research and were selectively exposed to a smoking-anticipation condition (cigarettes plus expectation of imminent smoking) following either 24 hr of tobacco withdrawal or ad libitum smoking. Results indicated that EEG asymmetry was increased by smoking anticipation and that smoking itself reduced EEG asymmetry. Results also suggested that smoking anticipation increased overall (bihemispheric) EEG activation. Results were interpreted in terms of major theories of drug motivation.

Gender differences in response to nicotine replacement therapy: objective and subjective indexes of tobacco withdrawal.

K. A. Perkins (1996) recently proposed that nicotine reinforcement controls smoking to a greater degree among men than women and that consequently, nicotine replacement therapy (NRT) during smoking cessation should benefit men more than women. The authors tested this hypothesis. Polysomnographic measures of sleep and self-report indexes of tobacco withdrawal were collected pre- and postcessation from an active nicotine patch group and a placebo patch group in a randomized, double-blind clinical trial (N = 34). Objective sleep parameters supported Perkins's hypothesis and indicated that among women, NRT may be less effective at suppressing certain withdrawal responses compared with men and may produce some iatrogenic effects. Valid and reliable self-report measures of withdrawal did not reveal gender differences in response to NRT.

Tobacco and alcohol abuse: clinical opportunities for effective intervention.

No behaviors are more costly to the United States from a health or economic perspective than tobacco and alcohol use. One of the primary strategies available to mitigate this exacting toll is to identify and clinically treat the 25% of adults in America who smoke and the 20% of adults who drink alcohol above recommended limits. During the last two decades, researchers have identified a series of brief clinical interventions that can markedly reduce alcohol and tobacco use and significantly decrease the health burdens resulting from such use. This review outlines office-based clinical interventions and the organizational policies that support these interventions that have been shown to decrease tobacco and alcohol use.

A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.