Palo Alto Center for Pulmonary Disease Prevention

Rationale: Not all individuals with tobacco dependence are ready to give up smoking. Research reveals behavioral differences between adults ready to discontinue tobacco use and those who are not. Thus, the interventions applied to these populations might differ. However, the evidence of using varenicline in individuals who are not ready to discontinue tobacco use is uncertain. Objectives: To determine if, in tobacco-dependent adults who report not being ready to discontinue tobacco use, clinicians should begin treatment with varenicline or wait until subjects are ready to discontinue tobacco use. Methods: We conducted a systematic review to assess the effectiveness and safety of treatment with varenicline in tobacco-dependent adults who are not ready to discontinue tobacco use. We systematically searched the Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials comparing varenicline versus placebo for individuals who were not ready to discontinue tobacco use. Outcomes of interest include point prevalence abstinence during treatment or at six months or longer, smoking reduction, motivation to quit, adverse events, and withdrawal symptoms. Two authors independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We followed the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of evidence. Results: Five trials met our inclusion criteria. All 2,616 participants were adults who were not ready to discontinue tobacco use at study entry. For 7-day point prevalence abstinence at six months or longer, high-certainty evidence suggested that varenicline increased abstinence compared with placebo (relative risk, 2.00 [95% confidence interval (CI), 1.70-2.35]; absolute risk reduction, 173 more per 1,000 [95% CI, 121 more to 234 more]). We identified moderate-certainty evidence suggesting that varenicline increased serious adverse events (relative risk, 1.75 [95% CI, 0.98-3.13]; absolute risk reduction, 12 more per 1,000 [95% CI, 0 fewer to 35 more]). For withdrawal, low-certainty evidence suggested that varenicline treatment was associated with a lower symptom score (mean difference, 1.54 points lower; 95% CI, 2.15-0.93 points lower; low certainty) assessed using the Brief Questionnaire of Smoking Urges. Conclusions: In tobacco-dependent adults who are not ready to discontinue tobacco use, initiating varenicline treatment results in a large increase in abstinence and likely results in a slight increase in serious adverse events.

Research into the health effects of soyfoods and soybean constituents has increased at a phenomenal pace over the past decade. This research includes a wide range of areas, such as cancer, coronary heart disease, osteoporosis, cognitive function, menopausal symptoms and renal function. Importantly, there are an increasing number of clinical studies being conducted in this field, which was quite evident from the findings presented at the Fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, November 4-7, 2001, in San Diego, California. There is no doubt that progress in understanding the health effects of soy is being made, but much of the data are frustratingly inconsistent. For example, there were conflicting results presented at the symposium on the role of isoflavones in bone health. Similarly, presentations painted an unclear picture of the role of isoflavones in cholesterol reduction. The relatively short duration and small sample size of many of the human studies in this field likely contribute to the inconsistent results. Although there are some controversies regarding the safety of soy for certain subsets of the population, special sessions at the symposium on breast cancer and cognitive function did much to alleviate concerns that soy could have detrimental effects in these areas. Furthermore, published data and new research presented at this meeting suggest that the consumption of even 10 g (typical of Asian intake) of isoflavone-rich soy protein per day may be associated with health benefits. If this modest amount of soy protein were to be incorporated in the American diet, it would represent only approximately 15% of total U. S. protein intake.

Abstract To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12Rβ1 and IL-12Rβ2 subunits, as well as IL-12Rβ2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-γ production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12Rβ1 and IL-12Rβ2 were significantly decreased, and IL-12Rβ2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-γ production is enhanced, IL-12Rβ2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-β enhanced IL-12Rβ1 and IL-12Rβ2 expression, and IFN-γ production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-β reduced IL-12Rβ1 and IL-12Rβ2 expression, as well as IFN-γ production. In combination with prior studies showing increased production of TGF-β by blood monocytes from tuberculosis patients, this suggests that increased TGF-β production is the underlying abnormality that reduces IL-12Rβ1 and IL-12Rβ2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-γ production in human tuberculosis, and that expression of IL-12Rβ1 and IL-12Rβ2 may play a central role in mediating a protective Th1 response.

Objective. To study gender and ethnic aspects in a population consisting of patients treated for non‐fatal firearm injuries at public hospitals in Stockholm, Sweden, during a period of 21 years. Design. Retrospective study. Ethnicity was defined as being a foreign‐born individual or a native Swede. The morbidity and criminality data were analysed with unconditional logistic regression and the mortality data were analysed by a proportional hazard model. Results. Females and foreign‐born persons were more often victims of attempted murder than males or native Swedes. Attempted suicide was more common among native Swedes. Male patients, single persons and Finnish immigrants treated for a firearm injury all showed an increased risk of being registered for criminality or committing a violent crime. There was no difference between native Swedes and foreign‐born persons concerning the number of hospitalisations during the follow‐up period. Living alone and being of male gender were associated with an increased risk of hospitalisation. Firearm victims, independently of ethnicity, had an increased mortality rate compared to a Swedish population; the standardised mortality ratio (SMR) for males was almost 3 and for females almost 8 compared to the SMR of 1 for the whole Swedish population. Conclusion. Firearm victims constitute a population at risk from social, psychological as well as from medical points of view. The present study shows an association between gender, ethnicity, criminality, and morbidity among firearm victims underlining the importance of ethnic‐ and gender‐specific violence prevention strategies.

To examine the effects of a community education and law enforcement intervention on illegal tobacco sales to minors. A 2-year, before and after trial with retail stores as the unit of analysis. Implementation occurred in four suburban California communities with populations of 25,000 to 100,000. All the retail stores in one intervention community and half the retail stores, randomly selected, in the other three intervention communities (n = 169) were visited by minors aged 14 to 16 years with the intent to purchase tobacco. Ongoing community and merchant education and four law enforcement operations were conducted. Over-the-counter and vending machine sales of tobacco to minors were the primary outcomes. Among a cohort of stores visited by minors at the pretest (n = 104) in June 1988, 71% sold tobacco over the counter and 92% sold tobacco through vending machines. At posttest 2 in May 1990, 24% sold tobacco over the counter and 93% sold tobacco through vending machines. Of the 31 stores issued citations, 16 were followed into the courts where the fines were dismissed or reduced. Education alone had a limited effect on reducing illegal tobacco sales to minors. It did promote community support for more aggressive enforcement strategies. Education plus enforcement decreased significantly over-the-counter sales; vending machine sales were unaffected by these interventions. The lack of support at the judicial level may temper the effectiveness of enforcement. Legislative remedies addressing judicial obstacles and vending machine sales are needed.

Low plasma high density lipoprotein (HDL) cholesterol concentration is a risk factor for coronary heart disease (CHD) and is frequently associated with high triglyceride concentration. Both of these abnormalities have been related to insulin resistance as estimated by plasma insulin concentrations and to measures of obesity, regional adiposity, and physical fitness. To determine which of these variables (fasting plasma insulin, obesity as measured by body mass index [BMI], or regional adiposity as measured by waist to hip ratio [WHR]) best identifies men with low HDL cholesterol and high triglyceride concentrations, we divided 83 men, aged 50-65 years, who were free of CHD or diabetes, into tertiles based on BMI, WHR, or fasting plasma insulin concentration. Only for plasma insulin tertiles were there statistically significant differences in HDL cholesterol (tertile 1, mean +/- SEM, 1.34 +/- 0.08 mmol/l; 2, 1.16 +/- 0.05 mmol/l; 3, 1.10 +/- 0.06 mmol/l; p less than 0.03) and triglyceride (tertile 1, 1.05 +/- 0.08 mmol/l; 2, 1.48 +/- 0.12 mmol/l; 3, 1.82 +/- 0.17 mmol/l; p less than 0.005) concentrations. In forward stepwise regressions with HDL cholesterol and triglyceride as dependent variables, fasting insulin concentration but not BMI, WHR, or maximal oxygen uptake (VO2max), a measure of physical fitness, predicted HDL cholesterol (R2 = 0.07, p less than 0.02) and triglyceride (R2 = 0.20, p less than 0.001) concentrations. The data suggest that plasma insulin concentration is an important predictor of HDL cholesterol and triglyceride concentrations independent of BMI, WHR, or VO2max.