Cork Newsletter. Medical Aspects. Winter 2003

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...on Substance Abuse Ð Medical Aspects

www.ProjectCork.org

Winter 2002/03

Alcohol consumption and the risk of diabetes by body mass index levels in a cohort of 5,636 Japanese.

Watanabe M; Barzi F; Neal B; Ueshima H; Miyoshi Y; Okayama A et al. Diabetes Research and Clinical Practice 57(3): 191-197, 2002. (32 refs.)
The association between alcohol consumption and the risk of diabetes in Japanese with a low-body mass index (BMI) (less than or equal to 22.0 k kg/M-2), middle-BMI (22.1-24.9 kg/M2) and high-BMI (greater than or equal to 25.0 kg/M2) was investigated among a cohort of 5,636 employees of a Japanese insurance company. Participants were free of diabetes at baseline and were followed up for a mean of 5.7 years with annual assess-ments of fasting plasma glucose (FPG). The outcome was a clinical diagnosis of diabetes on the basis of a questionnaire administered at each follow-up assessment or a follow-up FPG level of 7.8 mmol/l or more. Relative risks and 95% confidence intervals (95% CIs) were estimated by fitting pooled logistic regression models, which included age, gender, BMI, baseline FPG level, current tobacco use and current alcohol consump-tion. A total of 264 outcome events were recorded. The relative risk of diabetes associated with current alcohol consumption was 3.19 (95% CI 1.09-9.37) among low-BMI individuals, 0.41 (0.23-0.73) among middle-BMI individuals and 0.74 (0.44-1.25) among high-BMI individuals. In this study, current alcohol consumption was associated with an increased risk of diabetes among low-BMI individuals and a decreased risk of diabetes among middle-BMI individuals. A tendency for an association of alcohol consumption with a decreased risk of diabetes among high-BMI individuals was noted, although without statistical significance.

Birth to age 7 growth of children prenatally exposed to drugs: A prospective cohort study.

Covington CY; Nordstrom-Klee B; Ager J; Sokol R; Delaney-Black V. Neurotoxicology and Teratology 24(4): 489-496, 2002. (49 refs.)
Prenatal exposure to cocaine, alcohol, and cigarettes has been linked to decreased birth weight and length. Unclear, however, is whether growth deficits persist into childhood. Women who were pregnant, African-American, not HIV-positive, and who delivered singleton infants were extensively screened throughout pregnancy for cocaine, alcohol, cigarette, and other illicit drug use. Of the approximately 1100 eligible subjects, 665 families were located at a 7-year postbirth follow-up and 540 participated. After appropriate control for potential confounders and prenatal exposures, prenatal exposure to cocaine, alcohol, and cigarettes each independently predicted birth weight and length. At age 7, prenatal cocaine exposure was significantly related to height deficits after accounting for other prenatal exposures and significant confounders. Children at age 7 exposed to cocaine in utero were up to 1 in. shorter and twice as likely to fall below the 10th percentile in height as the control children after accounting for other significant confounders including other prenatal exposures. Maternal age moderated the relation between prenatal exposures and child growth. Children born to women over 30 and exposed to cocaine were up to 2 in. shorter and four times more likely to have clinically significant height deficits at age 7. Children of older women and exposed to moderate-to-high levels of alcohol prenatally were up to 14 lb lighter and five times more likely to fall below the 10th percentile in weight. Similar growth restriction was not associated with prenatal exposures for children born to younger mothers. These outcomes add to the growing body of literature detailing long-term effects of prenatal drug exposure, suggesting differential effects for cocaine and alcohol, and indicating that maternal age may moderate these effects. Mechanisms for growth restriction and failure of catch-up under conditions of prenatal exposures are presented, suggesting further study of these developmental outcomes.

Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: Results from a multisite study.

Anton RF; Lieber C; Tabakoff B. Alcoholism: Clinical and Experimental Research 26(8): 1215-1222, 2002. (59 refs.)
Background: The purpose of this article is to evaluate the biological marker of heavy alcohol use, carbohydrate-deficient transferrin (CDT), in contrast to the older and more widely used gamma- glutamyltransferase (GGT) for the detection and monitoring of heavy alcohol use. Methods: In this report, CDT and GGT sensitivity and specificity for heavy alcohol intake are examined in a large multisite study in which 444 recently admitted inpatient alcoholics were compared with 204 matched social drinker controls. In addition, changes in these biomarkers were evaluated during an initial abstinence period and biweekly over 14 weeks of monitoring to compare changes in CDT and GGT during continued abstinence or relapse. Results: CDT and GGT were comparable in identifying heavy alcohol consumption in men, but GGT appeared to be better for women. For both genders, when these markers were combined, there was better sensitivity than when used alone. CDT and GGT both decreased during 4 weeks of abstinence. When we used a 30% increase from baseline abstinent levels as an indicator, CDT appeared marginally better than GGT at indicating relapse in men but not in women. For men in particular, relapse over the course of the study was best identified by evaluating changes (30% increase) in both markers simultaneously. Conclusions: These results support the utility, of CDT, especially when used in conjunction with GGT, as an aid in detecting and monitoring heavy alcohol consumption.

Cognitive function after 11.5 years of alcohol use: Relation to alcohol use.

Leroi I; Sheppard JM; Lyketsos CG. American Journal of Epidemiology156(8): 747-752, 2002The authors investigated the relation between alcohol use and cognitive decline after 11.5 years in a com-munity sample. Findings were based on a study of 1,488 participants in the Baltimore arm of the Epidemiologic Catchment Area study, who completed the Mini-Mental State Examination (MMSE) at three time points in 1981, 1982, and 1993- 1996. The participants were divided into five groups based on the amount and frequency of alcohol intake and the Diagnostic and Statistical Manual of Mental Disorders: DSM IIIR diagnosis of alcohol use disorders. The relation between level of alcohol use and MMSE score change between waves 2 and 3 of the study was examined using analysis of variance, which was then adjusted for the effects of age, race, and education. Alcohol use was associated with significantly less cognitive decline in alcohol drinkers when compared with nondrinkers for both sexes. When adjusted, a trend toward significantly less cognitive decline was seen in women drinkers, but not in men. Among female users, there was a trend toward less cognitive decline in women who used alcohol habitually as compared with those who were nonusers or heavy users. The authors conclude that, over long time periods, alcohol use is not associated with cognitive decline and, in women, may be associated with less decline.

Cognitive functioning among infants of alcoholic fathers.

Leonard KE; Das Eiden R. Drug and Alcohol Dependence67(2): 139-147, 2002. (41 refs.)
Although there is considerable evidence that suggests that children of alcoholic fathers are at risk for maladaptive developmental outcomes, there is a large amount of heterogeneity in these outcomes. This study examined this hypothesis using broad measures of mental and language development during the toddler period as a function of fathers' alcoholism and associated risk factors. Participants included 102 families in which the father was alcoholic, 20 families in which the father was alcoholic and the mother was a heavy drinker and 104 control families matched in terms of maternal education, race/ethnicity, child gender, marital status and number of children. Families, in which the mother engaged in significant prenatal drinking or drug use, were excluded. Infants were tested at 12, 18 and 24 months old. Analyses revealed no significant differences between controls and infants of severe alcoholics, antisocial alcoholics, depressed alcoholics or family history positive alcoholics. There were also no differences between controls and infants in families with an alcoholic father/heavy drinking mother. The results suggest that overall mental development was not associated with paternal alcoholism. This raises the possibility that later problems in these areas may reflect more specific cognitive processes or the impact of parenting and behavioral problems among these children.

Collective poisoning with hallucinogenous herbal tea.

Balikova M. Forensic Science International 128(1/2): 50-52, 2002. (8 refs.)
An incident wherein more than 30 people were poisoned with a herbal infusion during a meditation session is des-cribed. The clinical features observed were hallucinations, agression, agitation, amnesia, mydriasis, dry skin, tachy-cardia. hyperthermia, hypotension, collapse, coma and respiratory depression. All patients recovered, although mechanical ventilation was required in some instances. A portion of the herbal infusion was found to contain atropine (hyoscyamine), scopolamine (hyoscine), harmine, and other alkaloids. The estimated ingested doses (free bases) were atropine 4 mg, harmine 27 mg, and scopolamine 78 mg. The mean concentrations in 21 serum samples obtained approxi-mately 6 h after ingestion of the infusion were atropine 5 ng/ml, harmine 8 ng/ml, and scopolamine 13 ng/ml.

Current and former marijuana use: Preliminary findings of a longitudinal study of effects on IQ in young adults.

Fried PA; Watkinson B; Gray R. Canadian Medical Association Journal166(7): 887-891, 2002. (34 refs.)
Background: Assessing marijuana's impact on intelligence quotient (IQ) has been hampered by a lack of evaluation of subjects before they begin to use this substance. Using data from a group of young people whom we have been following since birth, we examined IQ scores before, during and after cessation of regular marijuana use to determine any impact of the drug on this measure of cognitive function. Methods: We deter-mined marijuana use for seventy 17- to 20-year-olds through self-reporting and urinalysis. IQ difference scores were calculated by subtracting each person's IQ score at 9-12 years (before initiation of drug use) from his or her score at 17-20 years. We then compared the difference in IQ scores of current heavy users (at least 5 joints per week), current light users (less than 5 joints per week), former users (who had not smoked regularly for at least 3 months) and non-users (who never smoked more than once per week and no smoking in the past two weeks). Results: Current marijuana use was significantly correlated (p < 0.05) ill a dose-related fashion with a decline in IQ over the ages studied. The comparison of the IQ difference scores showed an average decrease of 4.1 points in current heavy users (p < 0.05) compared to gains in IQ points for light current users (5.8), former users (3.5) and non-users (2.6). Interpretation: Current marijuana use had a negative effect on global IQ score only in subjects who smoked 5 or more joints per week. A negative effect was not observed among subjects who had previously been heavy users but were no longer using the substance. We conclude that marijuana does not have a longterm negative impact on global intelligence. Whether the absence of a residual marijuana effect would also be evident in more specific cognitive domains such as memory and attention remains to be ascertained.

Etiology and weekly occurrence of alcohol-related seizures.

Rathlev NK; Ulrich A; Shieh TC; Callum MG; Bernstein E; D'Onofrio G. Academic Emergency Medicine 9(8): 824-828, 2002. (17 refs.)
Objectives: 1) To determine the prevalence of identifiable causes of alcohol-related seizures other than alcohol withdrawal. 2) To test the hypothesis that patients with alcohol-related seizures present with greater frequency following Sundays when alcohol is not commercially available. Methods: This was a retrospective chart review of 140 consecutive patients presenting with alcohol-related seizures during a six-month period. Identifiable causes of seizures other than alcohol withdrawal and the day of the week of presentation were documented. Results: One hundred forty individual patients were eligible for study. Identifiable causes of seizures other than alcohol withdrawal were found in 53.6% of patients, and they were distributed as follows: 1) current or past history of signify-cant head trauma 25.7%, 2) idiopathic seizure disorder 15.7%, 3) cerebrovascular accident 5.7%, 4) nontraumatic intracranial lesion 3.6%, and 5) toxic/metabolic abnormalities 2.9%. Alcohol is not available for purchase on Sundays because of the "Blue Laws" in Massachusetts. A total of 34.5% of patients with alcohol withdrawal seizures presented on Mondays (p < 0.001). Of patients with identifiable causes of seizures other than alcohol withdrawal, only 16% presented on Mondays (p > 0.10). Conclusions: Approximately 50% of seizures in alcohol-dependent patients are potentially unrelated to alcohol withdrawal. Patients with alcohol withdrawal seizures presented with greater frequency on Mondays following the 24-hour period when alcohol was not commercially available in Boston. This suggests that patients with alcohol withdrawal seizures may present with greater frequency following periods of decreased availability of alcohol.

Evidence that transient nicotine lowers the body weight set point.

Cabanac M; Frankham P. Physiology and Behavior 76(4/5): 539-542, 2002. (20 refs.)
Objective: Smokers usually gain weight when they quit smoking. The present work explores the hypothesis according to which such a rise is a behavioral response to a raised body weight set point taking place when nicotine is eliminated from the body. Research Methods and Procedures: The human body weight set point was assessed with classical behavioral and psychophysical methods, from the delay to experience negative alliesthesia when repeatedly ingesting sweet stimuli. Seven habitual smokers were tested once before lunch, after smoking (nonabstinent) as usual and once again after refraining from smoking (abstinent). Three additional nicotine-naive subjects were tested under the same procedure after receiving at 0730 h in the morning a trans-dermal nicotine patch (14 mg) or a placebo patch. Two of the subjects also received nicotine (7 mg) for a third session. Results: Oral and transdermal administration of nicotine did not decrease the initial pleasure or modify the initial palat-ability of eating sweet stimuli, but significantly accelerated the following onset of self-reported displeasure (negative alliesthesia) aroused by repeated ingestion of sweet stimuli. Discussion: These results are understood as an acute lowering of the body weight set point by nicotine. The body weight gain taking place after quitting smoking may, therefore, be explained by the removal of the lowering of the body weight set point induced by nicotine.

Hair morphine concentrations of fatal heroin overdose cases and living heroin users.

Darke S; Hall W; Kaye S; Ross J; Duflou J. Addiction 97(8): 977-984, 2002. (23 refs.)
Aims: To compare heroin and other opiate use of heroin overdose fatalities, current street heroin users and drug-free therapeutic community clients. Design: Hair morphine concentrations that assess heroin use and other opiate use in the 2 months preceding interview or death were compared between heroin overdose fatalities diagnosed by forensic pathologists (fOD) (n = 42), current street heroin users (CU) (n = 100) and presumably abstinent heroin users in a drug-free therapeutic community (TC) (n = 50). Setting Sydney, Australia. Findings The mean age and gender breakdown of the three samples were 32.3 years, 83% male (FOD), 28.7 years, 58% male (CU) and 28.6 years, 60% male (TC). The median blood morphine concentration among the FOD cases was 0.35 mg/l, and 82% also had other drugs detected. There were large differences between the three groups in hair morphine concentrations, with the CU group (2.10 ng/mg) having concentration approximately four times that of the FOD group (0.53 ng/mg), which in turn had a concentration approximately six times that of the TC group (0.09 ng/mg). There were no significant differences between males and females in hair concentrations within any of the groups. Hair morphine concentrations were correlated significantly with blood morphine concentrations among FOD cases (r = 0.54), and self-reported heroin use among living participants (r = 0.57). Conclusions The results indicate that fatal cases had a lower degree of chronic opiate intake than the active street users, but they were not abstinent during this period.

Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women.

Sellers TA; Vierkant RA; Cerhan JR; Gapstur SM; Vachon CM; Olson JE et al. Cancer Epidemiology, Biomarkers & Prevention 11(10 Part 1): 1104-1107, 2002. (26 refs.)
Alcohol intake is an established risk factor for breast cancer, but the underlying mechanism remains unknown. Four recent studies have described interactions of alcohol and low folate intake. We examined this interaction on the risk of postmenopausal breast cancer stratified by tumor receptor status for estrogen (ER) and progesterone (PR). The Iowa Women's Health Study is a prospective cohort study of 34,393 at-risk women. Alcohol use and folate intake from diet and supplements were estimated at baseline in 1986 through a semiquantitative food frequency questionnaire. Through 1999, 1,875 cases of breast cancer were identified through linkage to the Iowa Surveillance, Epidemiology, and End Results registry. Compared with nondrinkers with folate intakes above the 50(th) percentile, women with low folate and high alcohol were at 1.43-fold greater risk (1.02- 2.02). When stratified by tumor receptor status for ER or PR, the risks for low folate/high alcohol were 2.1 (1.18-3.85), 1.0 (0.76- 1.42), 1.2 (0.88-1.70), and 1.2 (0.69-2.02) for ER-, ER+, PR+, and PR- tumors, respectively. Because the results were limited primarily to ER- tumors, one plausible interpretation of these data is that alcohol influences breast cancer through its metabolite, acetaldehyde, rather than through effects on ER levels and receptor- mediated pathways.

Isopropyl alcohol intoxication: A diagnostic challenge. art. no. E12.

Zaman F; Pervez A; Abreo K. American Journal of Kidney Diseases 40(3): NIL_38-NIL_41, 2002. (14 refs.)
Isopropyl alcohol (IPA) Is an ingredient of commonly used household solutions. Accidental and suicidal ingestion of IPA sometimes can be fatal if it goes un-recognized and untreated. There are few published reports on IPA Intoxication. We describe a case of repeated IPA Ingestion In a single Individual, followed by a review of the literature on the subject. The differential diagnosis, diagnostic pitfalls, and therapeutic Interventions In patients with IPA Intoxications are discussed.

Maternal use of cannabis and pregnancy outcome.

Fergusson DM; Horwood LJ; Northstone K. British Journal of Obstetrics and Gynaecology 109(1): 21-27, 2002. (19 refs.)
Objective: To document the prevalence of cannabis use in a large sample of British women studied during pregnancy, to determine the association between cannabis use and social and lifestyle factors and assess any independent effects on pregnancy outcome. Design Self-completed questionnaire on use of cannabis before and during pregnancy. Sample Over 12,060 women expecting singletons at 18 to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of Pregnancy and Childhood. Methods: Any association with the use of cannabis before and during pregnancy with pregnancy outcome was examined, taking into account potentially confounding factors including maternal social back-ground and other substance use during pregnancy. Main outcome measures Late fetal and perinatal death, special care admission of the newborn infant, birthweight, birth length and head circumference. Results Five percent of mothers reported smoking cannabis before and/or during pregnancy; they were younger, of lower parity, better educated and more likely to use alcohol, cigarettes, coffee, tea and hard drugs. Cannabis use during pregnancy was unrelated to risk of perinatal death or need for special care, but, the babies of women who used cannabis at least once per week before and throughout pregnancy were 216g lighter than those of non-users, had significantly shorter birth lengths and smaller head circumferences. After adjustment for confounding factors, the association between cannabis use and birth-weight failed to be statistically significant (P = 0.056) and was clearly non-linear: the adjusted mean birthweights for babies of women using cannabis at least once per week before and throughout pregnancy were 90g lighter than the offspring of other women. No significant adjusted effects were seen for birth length and head circumference. Conclusions: The results of this study suggest that the use of cannabis during pregnancy was not associated with increased risk of perinatal mortality or morbidity in this sample. However, frequent and regular use of cannabis throughout pregnancy may be associated with small but statistically detectable decrements in birthweight.

Chronic disease mortality in a cohort of smokeless tobacco users.

Accortt NA; Waterbor JW; Beall C; Howard G. American Journal of Epidemiology 156(8): 730-737, 2002The purpose of this study was to characterize the relation between smokeless tobacco use and the risk of all-cause and disease-specific mortality. Using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, the authors assessed the 20-year mortality experience of smokeless tobacco users. Subjects aged 45 years or more at baseline (1971-1975) were categorized as either smokeless tobacco users (n=1,068) or non-smokeless tobacco users (n=5,737). Subjects were further stratified by smoking status and gender. Proportional hazard ratios were used to assess associations. After adjustment for confounders, no association between smokeless tobacco use and all-cause (hazard ratio=1.1, 95% confidence interval (CI): 0.9, 1.3), all cancer (hazard ratio=1.1, 95% CI: 0.6, 1.9), or all cardiovascular (hazard ratio=1.1, 95% CI: 0.8, 1.5) mortality was found. There was an increase in all cancer mortality of borderline significance among female smokeless tobacco users (hazard ratio=1.7, 95% CI: 1.0, 2.8). The lung cancer mortality rate among combined users (smokeless tobacco and cigarettes), based on the rates for exclusive smokeless tobacco users and exclusive smokers, was higher than expected, possibly because of heavier smoking among these subjects. The mortality experience of smokeless tobacco users was not significantly greater than that of non-tobacco users and was appreciably less than that of cigarette smokers. Furthermore, combined use of smokeless tobacco and cigarettes did not increase overall mortality beyond that expected from use of the individual products.

Narcotic-induced hypogonadism during therapy for heroin addiction.

Daniell HW. Journal of Addictive Diseases 21(4): 47-53, 2002Many patients receiving sustained-action narcotics during therapy for heroin addiction have symptoms of fatigue, depression, diminished libido, and impaired sexual function. They are rarely, however, evaluated for narcotic-induced hypogonadism, or treated with sex- hormone replacement. Studies are reviewed examining the influence of narcotic administration on sex-hormone levels. These document frequent, sometimes profound, deficiencies in many men and women treated with narcotics. We have documented improved quality of life during sex-hormone replacement therapy in patients with narcotic-induced hypogonadism, most of whom were receiving their narcotics for control of chronic pain. These studies suggest that similar hormone replacement therapy may assist patients receiving narcotics for treatment of heroin addiction.

Update on caffeine consumption, disposition and action.

Mandel HG. Food and Chemical Toxicology 40(9): 1231-1234, 2002. (16 refs.)
This report represents a current summary of the caffeine contents of various commercial products, and provides data on the spectrum of caffeine intake levels in man. A summary of the substance's pharmacokinetics describes information on its disposition in the body. The effects of caffeine are related to its interaction with adenosine receptors.

A new method of packaging cocaine for international traffic and implications for the management of cocaine body packers.

Pidoto RR; Agliata AM; Bertolini R; Mainini A; Rossi G; Giani G. Journal of Emergency Medicine 23(2): 149-153, 2002. (14 refs.)
Clinical outcome of cocaine body packers is considered unpredictable; there are no clear guidelines for the manage-ment of these patients. Their surveillance in casualty wards, where they are usually admitted during evacuation of the packets, can be very difficult. The authors refer to a new type of cocaine packet, allowing these patients to be managed with a more conservative approach than in the past, and report their experience with 161 body packers, observed from January 1999 to December 2000. They adopted a surveillance protocol providing only minimal medical inter-vention. Among 161 body packers, 142 (88.2%) evacuated the ingested packets without significant symptomatology. Warning symptoms were present in 19 (11.8%) patients. Three patients (1.9%) presented with marked anxiety but none had cocaine in the urine sample. Fifteen (9.3%) body packers complained of colicky pain, and all underwent plain X-ray studies of the abdomen. Ten (6.2%) of them without radiologic signs of intestinal occlusion recovered with food deprivation and medical treatment, while five (3.1%) underwent laparotomy, three patients (1.9%) for gastric occlusion and two (1.2%) for ileal occlusion. Only one patient (0.6%) had warning symptoms and a urine screen positive for cocaine metabolites. In three cases of gastric occlusion, a gastrotomy was accomplished. In two cases of ileal occlusion, and in the patient with cocaine intoxication, packets were milked into the cecum, and some into the descending colon and rectum, until anal expulsion, by gentle pulling. Type 4 packets represent a new method of cocaine packaging, carrying the possibility of treating these body packers more conservatively than those transporting previous type of packets. Surgical approach to intestinal occlusion also may be conservative, because distal propulsion of the packets can be accomplished without entering the intestine.

Serum sialic acid levels are increased during relapse to alcohol drinking: A pilot study.

Ponnio M; Sillanaukee P; Franck J. Alcoholism: Clinical and Experimental Research 26(9): 1365-1367, 2002. (8 refs.)
Background: Sialic acid has been suggested to be a potential marker for alcohol abuse. A previous study showed that sialic acid levels were significantly higher in serum among alcoholics as compared with social drinkers. In addition, serum sialic acid concentrations decreased after a treatment program aiming at abstinence. In this study, sialic acid was investigated as a possible marker for relapse to alcohol drinking. Methods: Serum from alcohol-dependent patients in out-patient treatment (n = 8) was analyzed for sialic acid by a colorimetric assay. A baseline sample was taken when the subject had been abstinent for longer than 4 weeks. A second sample was taken after relapse within 3 days after cessation of drinking. A relapse was defined as two or more days with daily drinking of more than 60 g of pure alcohol. Results: The sialic acid levels were significantly increased by 21% (median; range, 6-33%; p < 0.01; n = 8) after a relapse as compared with the level after 4 weeks or longer of abstinence. Conclusions: This study suggests that serum sialic acid levels are significantly increased even after a short period of heavy drinking and may be a potential marker for relapse.

Cancer of the larynx in non-smoking alcohol drinkers and in non-drinking tobacco smokers.

Bosetti C; Gallus S; Franceschi S; Levi F; Bertuzzi M; Negri E; Talamini R; La Vecchia C. British Journal of Cancer 87(5): 516-518, 2002. (17 refs.)
The separate effect of alcohol and tobacco on laryngeal cancer was analysed in two case-control studies from Italy and Switzerland, comprising 40 non-smoking and 68 non-drinking cases, and 160 non-smoking and 161 non-drinking controls. The multivariate odds ratio was 2.46 for heavy drinkers non-smokers, and 9.38 for current smokers non-drinkers.