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Biomedical subjects

Jon O Ebbert

Publications and source records attributed to Jon O Ebbert.

At least 19 recordsLinked to original sources

Role of the glutathione metabolic pathway in lung cancer treatment and prognosis: a review.

Inherent and acquired drug resistance is a cause of chemotherapy failure, and pharmacogenomic studies have begun to define gene variations responsible for varied drug metabolism, which influences drug efficacy. Platinum-based compounds are the most commonly used chemotherapeutic agents in the treatment of advanced stage lung cancer patients, and the glutathione metabolic pathway is directly involved in the detoxification or inactivation of platinum drugs. Consequently, genotypes corresponding to higher drug inactivation enzyme activity may predict poor treatment outcome. Available evidence is consistent with this hypothesis, although a definitive role for glutathione system genes in lung cancer prognosis needs to be elucidated. We present evidence supporting a role of the glutathione system in acquired and inherited drug resistance and/or adverse effects through the impact of either drug detoxification or drug inactivation, thus adversely effecting lung cancer treatment outcome. The potential application of glutathione system polymorphic genetic markers in identifying patients who may respond favorably, selecting effective antitumor drugs, and balancing drug efficacy and toxicity are discussed.

Antineoplastic Agents↗

The Fagerström Test for Nicotine Dependence-Smokeless Tobacco (FTND-ST).

Few nicotine dependence measures have been developed for smokeless tobacco (ST) users. Existing measures are limited by the requirement to rate the nicotine content of ST brands for which data is scarce or non-existent. We modified the Fagerström Test for Nicotine Dependence (FTND) for ST users, referred to this scale as the FTND-ST, and evaluated its characteristics in a population of 42 ST users. The correlation between the FTND-ST total score and the serum cotinine concentrations was 0.53 (p<0.001). Internal consistency reliability assessed using the coefficient alpha was 0.47. Correlations and the coefficient alpha are similar to those reported for commonly used nicotine dependence measures. Development and refinement of nicotine dependence measures for ST users are essential steps in order to advance the field of ST research.

Adult↗

Measuring nicotine dependence among smokeless tobacco users.

The objective of this study was to assess the concurrent validity of the FTQ-ST and the DIS-IV diagnosis of nicotine dependence among 68 adult ST users enrolled in a randomized, controlled clinical trial of bupropion SR. FTQ-ST scores were not found to differ between those with and without a current DIS-IV diagnosis of nicotine dependence (7.4+/-2.1 vs. 6.8+/-2.8, P=0.325). For all possible FTQ-ST cutoff scores, the observed agreement between the FTQ-ST and the DIS-IV was not found to be different from that expected due to chance. FTQ-ST total scores were positively correlated with serum cotinine (Spearman's r=0.40, P<0.001), amount of tobacco used (r=0.51 and r=0.41 for average dips/chews per day; average tins/pouches per week, respectively, P<0.001), and a reduced likelihood of abstinence at 3 months (OR=0.76, 95% C.I. 0.61-0.96; P=0.019). Participants meeting DIS-IV criteria had lower cotinine concentrations than those without this diagnosis (411+/-263 ng/ml vs. 493+/-246 ng/ml; P=0.042). Poor concordance was observed between the FTQ-ST and the DIS-IV in the assessment of nicotine dependence in ST users.

Adult↗

Complementary treatments for tobacco cessation: a survey.

Little information is available regarding the prevalence of use and interest in future use of complementary and alternative medicine (CAM) for tobacco cessation among tobacco users. We conducted a self-administered anonymous survey among 1,175 patients seen at a midwestern outpatient tobacco treatment specialty clinic between November 2003 and July 2005. Patient use of CAM for tobacco cessation, perceived efficacy of these treatments, and interest in future use of CAM were ascertained. Data were summarized using descriptive statistics, and logistic regression models were used to determine the characteristics associated with past CAM use or interest in future use of CAM for tobacco cessation. All of the patients who received the survey completed it. A total of 27% of patients reported previous use of CAM for tobacco cessation. The interventions most commonly used were hypnosis, relaxation, acupuncture, and meditation. CAM treatments most commonly perceived to be efficacious were yoga, relaxation, meditation, and massage therapy. A total of 67% of the patients reported interest in future use of CAM for tobacco cessation. The treatments of greatest interest for use in the future were hypnosis, herbal products, acupuncture, relaxation, and massage therapy. Female gender, previous use of conventional tobacco cessation products, previous use of CAM treatments, and a higher level of education were significantly associated with interest in future CAM use. The high level of interest in CAM among tobacco users underscores the need to conduct further research in this field.

Acupuncture↗

Efficacy of acupuncture for cocaine dependence: a systematic review & meta-analysis.

: BACKGROUND: Acupuncture is a commonly used treatment option for the treatment of addictions such as alcohol, nicotine and drug dependence. We systematically reviewed and meta-analyzed the randomized controlled trials of acupuncture for the treatment of cocaine addiction. METHODS: Two reviewers independently searched 10 databases. Unpublished studies were sought using Clinicaltrials.gov, the UK National Research Register and contacting content experts. Eligible studies enrolled patients with the diagnosis of cocaine dependence of any duration or severity randomly allocated to either acupuncture or sham or other control. We excluded studies of acupuncture methods and trials enrolling patients with polysubstance use or dependence. We abstracted data on study methodology and outcomes. We pooled the studies providing biochemical confirmation of cocaine abstinence. RESULTS: Nine studies enrolling 1747 participants met inclusion criteria; 7 provided details for biochemical confirmation of cocaine abstinence. On average, trials lost 50% of enrolled participants (range 0-63%). The pooled odds ratio estimating the effect of acupuncture on cocaine abstinence at the last reported time-point was 0.76 (95% CI, 0.45 to 1.27, P = 0.30, I2 = 30%, Heterogeneity P = 0.19). CONCLUSION: This systematic review and meta-analysis does not support the use of acupuncture for the treatment of cocaine dependence. However, most trials were hampered by large loss to follow up and the strength of the inference is consequently weakened.

Journal Article↗

Iqmik--a form of smokeless tobacco used by pregnant Alaska natives: nicotine exposure in their neonates.

OBJECTIVE: To determine the concentration of nicotine and cotinine in maternal blood and neonatal cord blood among pregnant Alaska Native women and to assess the neonates for neurobehavioral effects. METHODS: In a nonrandomized, clinical observational pilot trial, 60 pregnant Alaska Native women were enrolled for assessment of Iqmik (a mixture of leaf tobacco and ash) and other tobacco use during pregnancy and at delivery. Neonatal cord blood, nicotine and cotinine concentrations were obtained, and neonatal neurobehavioral effects were assessed using the Lipsitz scale. RESULTS: At delivery, there were 22 subjects who reported using only Iqmik, and 10 who used other tobacco products. Subjects who reported using only Iqmik prior to delivery had higher concentrations of cotinine (167+/-116 vs. 81+/-100) in maternal blood (rank sum test, p=0.036) and higher concentrations of nicotine (8.4+/-7.3 vs. 4.4+/-5.1, p=0.048) and cotinine (153+/-115 vs. 70+/-95, p=0.048) in cord blood compared to subjects who reported using other tobacco products. Neurobehavioral signs as assessed by the Lipsitz score were increased in neonates born to mothers using only Iqmik (3.7+/-1.8, p=0.011), or to mothers using other tobacco products (3.4+/-1.4, p=0.034) compared to neonates born to women who reported no tobacco use (1.8+/-1.4). CONCLUSIONS: Mothers who use Iqmik and their neonates have higher cotinine concentrations compared to mothers who use cigarettes and/or other forms of tobacco. Neurobehavioral signs occur in neonates born to women who use Iqmik but also in neonates born to mothers who use other forms of tobacco during pregnancy.

Adult↗

Cochrane systematic reviews in acupuncture: methodological diversity in database searching.

BACKGROUND: Since the early 1970s, the efficacy of acupuncture for treating clinical conditions has been evaluated in several hundred randomized trials. Results from these trials have been synthesized in systematic reviews. A well-designed systematic review provides the highest level of evidence for establishing the efficacy of a clinical intervention. OBJECTIVES: The present study assesses the source of original literature contributing to Cochrane reviews on acupuncture. Databases searched to retrieve original studies are evaluated. The distribution of controlled trials in acupuncture across different topic areas and journals, the ability of the reviews to provide conclusive results, and the proportion of original studies indexed with MEDLINE are evaluated. METHODS: Systematic reviews on acupuncture were extracted from the Cochrane Database of Systematic Reviews. The key search term used was "acupuncture." When more than one systematic review was retrieved on the same topic, the most recent review was included. Indexing of individual clinical trials with MEDLINE was searched using the Single Citation Matcher in PubMed. RESULTS: A total of 94 papers were retrieved from the Cochrane database, of which 10 were included in the analysis. The most common subject areas were related to chronic pain. Considerable heterogeneity was observed in the number of databases searched (median 5, range 3-12). A total of 69% (74/108) papers were indexed with PubMed. Only 13% (14/108) of the papers were published in the primary acupuncture journals. Conclusive statements about the efficacy of acupuncture were made in only 2 of the 10 systematic reviews. CONCLUSIONS: Considerable methodological diversity exists in the comprehensiveness of database searches for Cochrane systematic reviews on acupuncture. This diversity makes the reviews prone to bias and adds another layer of complexity in interpreting the acupuncture literature.

Abstracting and Indexing↗

The association of alcohol consumption with coronary heart disease mortality and cancer incidence varies by smoking history.

OBJECTIVE: To evaluate the effect of alcohol on coronary heart disease (CHD), cancer incidence, and cancer mortality by smoking history. DESIGN/SETTING: A prospective, general community cohort was established with a baseline mailed questionnaire completed in 1986. PARTICIPANTS: A population-based sample of 41,836 Iowa women aged 55-69 years. MEASUREMENTS: Mortality (total, cancer, and CHD) and cancer incidence outcomes were collected through 1999. Relative hazard rates (HR) were calculated using Cox regression analyses. MAIN RESULTS: Among never smokers, alcohol consumption (> or =14 g/day vs none) was inversely associated with age-adjusted CHD mortality (HR, 0.40; 95% confidence interval [CI], 0.19 to 0.84) and total mortality (HR, 0.71; 95% CI, 0.55 to 0.92). Among former smokers, alcohol consumption was also inversely associated with CHD mortality (HR, 0.45; 95% CI, 0.23 to 0.88) and total mortality (HR, 0.78; 95% CI, 0.62 to 0.97), but was positively associated with cancer incidence (HR, 1.25; 95% CI, 1.03 to 1.51). Among current smokers, alcohol consumption was not associated with CHD mortality (HR, 1.05; 95% CI, 0.73 to 1.50) or total mortality (HR, 1.07; 95% CI, 0.92 to 1.25), but was positively associated with cancer incidence (HR, 1.30; 95% CI, 1.10 to 1.54). CONCLUSIONS: Health behavior counseling regarding alcohol consumption for cardioprotection should include a discussion of the lack of a decreased risk of CHD mortality for current smokers and the increased cancer risk among former and current smokers.

Aged↗

Motivation for stopping tobacco use among emergency department patients.

OBJECTIVES: To determine the feasibility of new models for reinforcing tobacco-use-cessation interventions initiated in the emergency department (ED). The authors assessed the level of motivation to quit tobacco use among a general population of ED patients; the proportion who receive tobacco-use assessments, information, and interventions from ED providers; and the desired timing of tobacco-use interventions. METHODS: Face-to-face interviews with a convenience sample of 376 adult patients receiving care in the ED at the Mayo Clinic in Rochester, Minnesota. RESULTS: Of the 376 participants, 27% (100/376; 95% CI = 22% to 31%) currently used one or more forms of tobacco. Thirty percent (30/100; 95% CI = 21% to 40%) of tobacco users were in the preparation stage of change for tobacco cessation. The median score on the Contemplation Ladder was 6 (range: 0-10). Twenty-seven percent (27/100; 95% CI = 19% to 37%) of all tobacco users would have been interested in a tobacco-use treatment after the ED visit, such as telephone-based counseling. Of the current tobacco users either receiving or desiring a tobacco-use intervention, 74% (25/34; 95% CI = 56% to 87%) would be interested in receiving an intervention component after the ED visit. CONCLUSIONS: ED patients who use tobacco demonstrate motivation to quit and express interest in receiving interventions to assist them after the ED visit. Previous investigations have observed that ED patients do not attend interventions prescribed after the initial ED encounter. These findings suggest that the development of new models for reinforcing tobacco-use interventions initiated in the ED deserve exploration, such as linking them to a tobacco quitline.

Adult↗

Alpha1-antitrypsin and neutrophil elastase imbalance and lung cancer risk.

OBJECTIVE: Imbalance between alpha(1)-antitrypsin and neutrophil elastase is an underlying cause of lung tissue damage that may create a favorable host environment for carcinogenesis. We conducted a case-control study to investigate whether genetic variations indicative of alpha(1)-antitrypsin deficiency (A1ATD) or an excess of neutrophil elastase modify lung cancer risk DESIGN: The case patients were 305 consecutively identified primary lung cancer patients, and the control subjects were 338 community residents. Protease inhibitor-1 (PI1), encoding alpha(1)-antitrypsin, was typed by an isoelectric focusing assay. Neutrophil elastase-2 (ELA2), encoding neutrophil elastase, was typed by two single-nucleotide polymorphism sites. Multivariable logistic regression models tested the independent and interactive effects of PI1, ELA2, tobacco smoke exposure, COPD, and family history of lung cancer RESULTS: Sex and ethnicity were comparable between case patients and control subjects, but case patients were more likely to be smokers, and to have a history of COPD, environmental tobacco smoke exposure, and a positive family history of lung cancer. Haplotype analysis indicated an overall strong association between the two ELA2 markers and lung cancer risk. Our best-fitting model showed significant and independent effects of the PI1-deficient allele (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 3.0) and the ELA2 T-G haplotype (OR, 4.1; 95% CI, 1.9 to 8.9) on lung cancer risk, and an increased risk (OR, 2.6; 95% CI, 2.4 to 2.8) for individuals carrying both a PI1-deficient allele and a G-G haplotype CONCLUSIONS: Genotypes indicative of A1ATD and/or an excess of neutrophil elastase are significantly associated with lung cancer risk. Our findings may provide opportunities to better understand the mechanisms of lung cancer development and risk reduction.

Aged↗

Cotinine as a biomarker of systemic nicotine exposure in spit tobacco users.

Unlike cigarette smokers, spit tobacco (ST) users absorb a significant amount of nicotine through the gastrointestinal tract while swallowing tobacco juice. The majority of the absorbed nicotine is rapidly converted to cotinine during first-pass hepatic metabolism. This process potentially compromises the utility of cotinine as a biomarker for systemic nicotine exposure in ST users. To investigate this question, we correlated nicotine and cotinine concentrations with clinical measures of ST use in 68 daily ST users enrolled in a non-nicotine pharmacologic intervention trial. We found that a higher frequency of swallowing tobacco juice (P=.007) was an independent predictor of higher serum cotinine concentrations. Serum nicotine concentrations, on the other hand, were not correlated with a higher frequency of swallowing. In the absence of a reliable way to measure frequency of swallowing, we conclude that cotinine should not be used for guiding clinical decisions that depend upon a precise quantification of systemic nicotine exposure, such as tailored nicotine replacement therapy.

Adult↗

Residential treatment for smokeless tobacco use: a case series.

We developed and implemented a novel 8-day residential treatment program for smokeless tobacco (ST) use. A multidisciplinary team delivered behavioral treatment, nicotine patches were adjusted to achieve 100% replacement of baseline peak serum nicotine concentrations, and bupropion sustained-release was prescribed. Mean participant age (+/- SD) was 47.4 +/- 18.2 years. Mean nicotine patch dose at program end was 43.2 mg/day +/- 13.9 (range 14 to 66 mg/d). Median percent replacement by serum nicotine concentrations was 86.6% (IQR: 75-113.8%). At 1 year, the biochemically-confirmed (urine anabasine <2.0 ng/mL) self-reported 7-day point prevalence tobacco abstinence rate was 58% (14/24). A residential treatment program for ST users may be effective. More research is needed to replicate our findings and determine if comparable abstinence rates can be achieved with outpatient ST treatment programs using similar behavioral and pharmacotherapies.

Administration, Cutaneous↗

Smokeless tobacco: an emerging addiction.

Smokeless tobacco (ST) use is an important health issue in the United States, and chronic use leads to significant morbidity. ST users are exposed to levels of nicotine comparable with smokers and experience symptoms of nicotine withdrawal when attempting to stop. Clinical treatment of ST users requires an understanding of the unique characteristics of ST. This article reviews ST products, epidemiology, pharmacology, health risks, and treatment approaches.

Humans↗

The relationship between cigarette smoking and quality of life after lung cancer diagnosis.

STUDY OBJECTIVE: To describe the relationship between cigarette smoking and quality of life (QOL) among lung cancer survivors as measured by the lung cancer symptom scale (LCSS). DESIGN AND SETTING: The LCSS was mailed to eligible patients (1,506 patients) between 1999 and 2002. LCSS scores (total and individual QOL components) were compared among different groups of cigarette smokers via univariate independent group testing and multivariate linear models. The modeling process examined group differences adjusted for age, gender, stage, and time of LCSS assessment. LCSS scores were transformed onto a scale of 0 to 100 points in which higher LCSS scores corresponded to a lower QOL. A 10-point difference between groups was defined a priori as being clinically significant. RESULTS: At the time of lung cancer diagnosis, 18% of the patients were never-smokers, 58% were former smokers, and 24% were current smokers. Among survey respondents completing the LCSS at follow-up assessment (1,028 respondents), the mean age was 65.2 years (SD, 10.8 years) and 45% were women. Thirty percent of baseline current smokers continued to smoke at the time of the follow-up assessment (ie, persistent smokers). The adjusted mean total LCSS scores for never-smokers and persistent smokers were 17.6 (SD, 4.02) and 28.7 (SD, 5.09), respectively (p < 0.0001). Seven of the individual LCSS QOL components (ie, appetite, fatigue, cough, shortness of breath, lung cancer symptoms, illness affecting normal activities, and overall QOL) were clinically and statistically (p < 0.001) different between never-smokers and persistent smokers. No clinically significant differences were noted for pain or hemoptysis. Former smokers had intermediate LCSS scores. No dose-response trends were observed between the number of packs of cigarettes smoked per day or the total number of pack-years smoked and the adjusted scores. CONCLUSION: The hypothesized relationship between smoking status and QOL was supported by this correlational study. Our findings suggest that persistent cigarette smoking after a lung cancer diagnosis negatively impacts QOL scores.

Adult↗

Using advanced search tools on PubMed for citation retrieval.

PubMed (www.pubmed.gov) provides health care professionals with free access to one of the largest searchable biomedical databases available. However, attempting to find relevant literature in PubMed without an understanding of basic search strategies and tools may be daunting and frustrating. In a previous issue of the Mayo Clinic Proceedings, we presented an overview of searching in PubMed and introduced its basic features. In this article, we build on this foundation and present advanced search tools designed to assist clinicians in performing efficient and focused literature searches.

Information Storage and Retrieval↗