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Biomedical subjects

K M Conigrave

Publications and source records attributed to K M Conigrave.

16 recordsLinked to original sources

The effect of total body water on the relationship between alcohol consumption and carbohydrate-deficient transferrin.

BACKGROUND: Clinicians agree that alcoholism commonly is overlooked in their patients, and that treating the symptoms without directing therapy to the underlying cause at best delays an inevitable decline in the patient's general health and well-being. The current analysis focused on carbohydrate-deficient transferrin (CDT), a promising biological marker of dangerous alcohol consumption. METHODS: Included in our study were men (730) and women (613) from study sites in Canada, Brazil, and Japan. All subjects were participants in the WHO/ISBRA Study on State and Trait Markers of Alcoholism, who completed an extensive demographic, medical, and behavioral survey and provided blood samples for determination of CDT levels. ANOVA and chi2 test for equality were used to examine the effect of total body water (TBW) on the alcohol consumption/CDT relationship. To examine whether accounting for differences in TBW improved the diagnostic properties of CDT when used as a state marker for alcohol consumption, odds ratios were calculated for men and women separately. RESULTS: Our results show that accounting for individual differences in TBW significantly influenced the alcohol consumption/CDT dose-response relationship. The effect of TBW was different for men compared with women. When we used a consumption cutoff value of 40 g/day and the CDTect recommended cutoffs (20 for men; 27 for women), adjusting for differences in TBW significantly increased diagnostic performance of CDT in men but not women. CONCLUSIONS: The dependence of CDT measures on body water content needs to be taken into account to maximize the performance of CDT as an effective state marker of alcohol consumption in males.

Adolescent↗

Cost effectiveness of brief interventions for reducing alcohol consumption.

The direct costs and health effects of a primary-care-based brief intervention for hazardous alcohol consumption were examined. The total cost of the intervention was calculated from costs associated with: marketing the intervention programme; providing training and support in the use of the intervention materials; physician time required for providing brief advice for 'at-risk' drinkers. The effect of the intervention on health outcomes was expressed in terms of number of life years saved by preventing alcohol-related deaths. This was derived by combining estimates of the impact of the programme if it were implemented nationally with available evidence on the health effects of excess alcohol consumption. Results are based on international trial evidence showing the physical resources required by the intervention and its effectiveness combined with Australian price data. The costs associated with screening and brief advice using the current intervention programme range from Aus$19.14 to Aus$21.50. The marginal costs per additional life year saved were below Aus$1873. The robustness of the model used is supported by an extensive sensitivity analysis. In comparison with existing health promotion strategies the costs and effects of the current intervention are highly encouraging.

Alcohol Drinking↗

WHP/ISBRA study on state and trait markers in alcoholism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Boris Tabakoff. The presentations were (1) Overview of the WHO/ISBRA study on state and trait markers in alcoholism, by Boris Tabakoff; (2) Biochemical markers of acute and chronic drinking: Results of the WHO/ISBRA study, by Anders Helander; (3) The impact of country of recruitment and body mass index on biological marker dose-response curves in the WHO/ISBRA Study, by Kate M. Conigrave; (4) Relationship of body water to carbohydrate-deficient transferrin measures, by Larry Martinez; and (5) Platelet adenylyl cyclase activity as a trait marker of alcohol dependence, by Paula L. Hoffman.

Adenylyl Cyclases↗

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Alcohol Drinking↗

A prospective study of drinking patterns in relation to risk of type 2 diabetes among men.

Using data from a 12-year prospective study, we determined the importance of the pattern of alcohol consumption as a risk factor for type 2 diabetes in a cohort of 46,892 U.S. male health professionals who completed biennial postal questionnaires. Overall, 1,571 new cases of type 2 diabetes were documented. Compared with zero alcohol consumption, consumption of 15-29 g/day of alcohol was associated with a 36% lower risk of diabetes (RR = 0.64; 95% CI 0.53-0.77). This inverse association between moderate consumption and diabetes remained if light drinkers rather than abstainers were used as the reference group (RR = 0.60, CI 0.50-0.73). There were few heavy drinkers, but the inverse association persisted to those drinking >/=50 g/day of alcohol (RR = 0.60, CI 0.43-0.84). Frequency of consumption was inversely associated with diabetes. Consumption of alcohol on at least 5 days/week provided the greatest protection, even when less than one drink per drinking day was consumed (RR = 0.48, CI 0.27-0.86). Compared with infrequent drinkers, for each additional day per week that alcohol was consumed, risk was reduced by 7% (95% CI 3-10%) after controlling for average daily consumption. There were similar and independent inverse associations for beer, liquor, and white wine. Our findings suggested that frequent alcohol consumption conveys the greatest protection against type 2 diabetes, even if the level of consumption per drinking day is low. Beverage choice did not alter risk.

Adult↗

Platelet adenylyl cyclase activity as a trait marker of alcohol dependence. WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical Research on Alcoholism.

BACKGROUND: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/ psychiatric variables, drinking and smoking history, and age and body weight on AC activity. METHODS: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. RESULTS: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. CONCLUSIONS: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.

Adenylyl Cyclases↗

Should we use carbohydrate-deficient transferrin instead of gamma-glutamyltransferase for detecting problem drinkers? A systematic review and metaanalysis.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) has been used as a test for excessive alcohol consumption in research, clinical, and medico-legal settings, but there remain conflicting data on its accuracy, with sensitivities ranging from <20% to 100%. We examined evidence of its benefit over a conventional and less expensive test, gamma-glutamyltransferase (GGT), and compared the accuracy of different CDT assay methods. METHODS: We performed a systematic review using summary ROC analysis of 110 studies prior to June 1998 on the use of CDT in the detection of alcohol dependence or hazardous/harmful alcohol use. RESULTS: We identified several potential sources of bias in studies. In studies examining CDT and GGT in the same subjects, subject characteristics were less likely to influence the comparison. In such paired studies, the original Pharmacia CDT assay was significantly more accurate than GGT, but the modified CDTect assay did not perform as well as the original and was not significantly better than GGT. The accuracy of the AXIS %CDT assay was statistically indistinguishable from modified CDTect. Several CDT assay methods appeared promising, in particular, liquid chromatography (chromatofocusing, HPLC, fast protein liquid chromatography) and isoelectric focusing, but there were insufficient paired studies from which to draw firm conclusions. CONCLUSIONS: In studies published before June 1998, the results obtained with commercially available CDT assays were not significantly better than GGT as markers of excessive alcohol use in paired studies. Further high-quality studies comparing CDTect (modified) and other CDT assays with GGT in the same subjects are needed.

Age Factors↗

The New South Wales Driver Assessment Programme: a pilot programme for assessment of drink drivers.

The NSW Driver Assessment Programme operated in Sydney from 1991-94 as a pilot scheme for the medical assessment of drink driver offenders. In this report we describe its functioning and characterize its 2267 participants. Offenders who had been convicted of driving with a blood alcohol concentration of 0.15 g/dL or more, or of refusing a breath test were referred to one of five Driver Assessment Clinics in Sydney. Medical assessment was mandatory before the driver's licence could be renewed. Of the 2267 offenders referred to the Programme, 922 (41%) attended an assessment during the operation of the scheme, with non-attenders having longer disqualification periods than attenders. Among attenders, 691 (75%) were judged fit to drive (i.e. "passed"). There was no significant variation in pass rate between centres. Of the 112 offenders who had laboratory results available from both first and second assessments, 68 (61%) showed a significant reduction in gamma glutamyltransferase (GGT) levels. We conclude that there was evidence of health benefit from the Programme in the fall in GGT levels in 61% repeat attenders. To assess the effects of the scheme on road safety would require prospective data collection on recidivism, road traffic accidents and, if possible, on self-reported drink-driving behaviour.

Journal Article↗

The AUDIT questionnaire: choosing a cut-off score. Alcohol Use Disorder Identification Test.

The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item questionnaire designed by the World Health Organization to screen for hazardous alcohol intake in primary health care settings. In this longitudinal study we examined its performance in predicting alcohol-related harm over the full range of its scores using receiver operating characteristic analyses. Three hundred and thirty ambulatory care patients were interviewed using a detailed assessment schedule which included the AUDIT questions. After 2-3 years, subjects were reviewed and their experience of alcohol-related medical and social harm assessed by interview and perusal of medical records. AUDIT was a good predictor of both alcohol-related social and medical problems. Cut-off points of 7-8 maximized discrimination in the prediction of trauma and hypertension. Higher cut-offs (12 and 22) provided better discrimination in the prediction of alcohol-related social problems and of liver disease or gastrointestinal bleeding, but high specificity was offset by reduced sensitivity. We conclude that the recommended cut-off score of eight is a reasonable approximation to the optimal for a variety of endpoints.

Adult↗

Predictive capacity of the AUDIT questionnaire for alcohol-related harm.

The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item questionnaire designed to screen for hazardous and harmful alcohol consumption. We examined its ability to predict alcohol-related illness and social problems, hospital admission and mortality over a 2-3-year period. At initial interview, 330 ambulatory care patients were assessed using a detailed interview including the AUDIT questions and laboratory tests. After 2-3 years, 250 (76%) subjects were reassessed and their experience of alcohol-related harm determined. Of those who scored eight or more on AUDIT at initial interview, 61% experienced alcohol-related social problems compared with 10% of those with lower scores (p < 0.0001); they also had a significantly greater experience of alcohol-related medical disorders and hospitalization. AUDIT score was a better predictor of social problems and of hypertension than laboratory markers. Its ability to predict other alcohol-related illnesses was similar to the laboratory tests. However, gamma glutamyltransferase was the only significant predictor of mortality. We conclude that AUDIT should prove a valuable tool in screening for hazardous and harmful alcohol consumption so that intervention can be provided to those at particular risk of adverse consequences.

Adult↗

Diagnostic tests for alcohol consumption.

A variety of laboratory tests are available to assist in the diagnosis of hazardous alcohol consumption and related disorders. Standard tests, such as serum gamma glutamyltransferase activity and erythrocyte mean cell volume, have limited sensitivity, particularly in detecting non-dependent hazardous consumption. Most also have poor specificity in that results are affected by common diseases and medications. Over the past 10 years a number of new laboratory tests have emerged. One of these, carbohydrate deficient transferrin, has high sensitivity in detecting persons with alcohol dependence, and shows promise for identification of non-dependent hazardous drinking; it is also highly specific. Others such as measurement of bound acetaldehyde, serum beta-hexosaminidase and the ratio of urinary serotonin metabolites offer promise in detecting recent heavy drinking. However, many issues remain unresolved. The newer markers have often been judged by contrasting their values in patients who are clearly alcohol dependent and abstainers or very light drinkers. It is now apparent that some are relatively insensitive markers of hazardous consumption. Future research needs to examine the performance of these markers among subjects with a range of alcohol intakes to fully determine their value in assessing drinking history. In addition, assays which are capable of some degree of automation need to be developed for analysing large numbers of samples.

Alanine Transaminase↗

Carbohydrate deficient transferrin levels in hazardous alcohol consumption.

Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (> 100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; P < 0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.

Adult↗

Prediction of alcohol-related harm by laboratory test results.

We examined the value of laboratory markers of excessive alcohol (ethanol) intake as predictors of mortality, morbidity, and health-care utilization in a cohort of 330 patients attending an acute ambulatory care service. Among men, all four markers examined--gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) activities, high-density lipoprotein cholesterol (HDL-C), and mean corpuscular volume (MCV)--were predictive of medical sequelae and health-care utilization over a 3-year period. In contrast, social problems were more closely related to the amount of alcohol consumption at initial assessment than to any biological marker. Serum GGT and AST activities and MCV were predictive of medical sequelae in women. The predictive value of GGT was an independent risk factor and did not merely reflect recent alcohol intake or the presence of chronic liver disease. We conclude that these readily available laboratory tests provide important prognostic information and should be an integral part of the assessment of persons with hazardous alcohol consumption.

Alcoholism↗

Problem drinking in emergency department patients: the scope for early intervention.

OBJECTIVE: To determine the prevalence of previously undiagnosed problem drinking and thereby to assess the suitability of the emergency department for early intervention. DESIGN: Three hundred and fifty ambulatory care patients were assessed by means of a structured interview schedule, physical examination and blood tests. Alcohol intake and presence of alcohol-related problems were recorded, along with history of past advice on drinking and self-perception of an alcohol problem. SETTING: The ambulatory care section of the emergency department of Royal Prince Alfred Hospital, Sydney. PATIENTS: Three hundred and fifty subjects, aged between 18 and 55 years, were sequentially selected over an 18-month period. RESULTS: Forty-one per cent of subjects (95% confidence interval, 36%-46%), 50% of men and 26% of women, were classified as problem drinkers on the basis of hazardous or harmful levels of alcohol consumption, frequent drinking to intoxication, evidence of dependence, or experience of alcohol-related problems. Of these, 63% had not previously received advice on drinking from a health professional and only 28% perceived they had a problem. Of particular note was that 24% of men and 4% of women were drinking 12 or more drinks (120 g of alcohol or more) in a single session on a weekly or more frequent basis. CONCLUSIONS: Many of the problem drinkers attending the emergency department have not previously received advice about their drinking from a health professional. The emergency department therefore offers considerable potential as a site for early detection and intervention in patients with hazardous and harmful alcohol use and related disorders.

Adult↗

Early identification of alcohol problems.

A high proportion of patients seen in clinical practice have an underlying alcohol problem. This is often difficult to detect, but failure to make the diagnosis may result in unnecessary investigations and inappropriate treatment. Furthermore, there is now good evidence of the effectiveness of brief intervention for problem drinking when it is still at an early stage. Several questionnaires and procedures based on clinical examination findings and laboratory tests are available to help in early diagnosis. They can be incorporated into the standard medical assessment and form the basis for screening programs for health risk factors.

Alcoholism↗

Patterns of drinking in Thai men.

Alcohol problems have increased considerably in Thailand in recent years, in common with many other countries in South East Asia. Little is known about the patterns or contexts of alcohol consumption in these countries, and so efforts to develop preventative strategies have been hampered. To identify current patterns related to alcohol consumption, we recruited 91 alcohol-dependent subjects, 77 hazardous or harmful drinkers, and 144 abstainers or light drinkers. A structured interview incorporating the World Health Organization 'tri-level' method to determine the amount and frequency of drinking, and the Alcohol Use Disorders and Associated Disabilities to diagnose alcohol dependence and harmful drinking was used. Median alcohol intake was 75 and 49 g/drinking day in the alcohol-dependent and harmful or hazardous groups respectively. The former group drank on average 25 days/month, whereas the harmful or hazardous drinkers drank 10 days/month. Drinking alone was more common in the alcohol-dependent group (67%), whereas harmful or hazardous drinkers typically drank with friends (58%), and infrequent drinkers drank only at social functions (61%). Only 28% of alcohol-dependent subjects perceived themselves as dependent on alcohol. The alcohol-dependent subjects and hazardous or harmful drinkers were more likely to currently smoke cigarettes and have a history of marijuana use than were non-drinkers, infrequent or light drinkers. Antisocial personality disorder was more commonly associated with alcohol dependence. In conclusion, alcohol dependence was characterized by continual drinking, whereas hazardous or harmful consumption was associated with an intermittent pattern. Other forms of substance use and personality disorder were associated with alcohol dependence. Clearer understanding of these factors would be of great benefit in planning an intervention programme for excessive drinking in Thailand.

Adult↗