Missing value imputation in longitudinal measures of alcohol consumption

Attrition in longitudinal studies can lead to biased results. The study is motivated by the unexpected observation that alcohol consumption decreased despite increased availability, which may be due to sample attrition of heavy drinkers. Several imputation methods have been proposed, but rarely compared in longitudinal studies of alcohol consumption. The imputation of consumption level measurements is computationally particularly challenging due to alcohol consumption being a semi-continuous variable (dichotomous drinking status and continuous volume among drinkers), and the non-normality of data in the continuous part. Data come from a longitudinal study in Denmark with four waves (2003-2006) and 1771 individuals at baseline. Five techniques for missing data are compared: Last value carried forward (LVCF) was used as a single, and Hotdeck, Heckman modelling, multivariate imputation by chained equations (MICE), and a Bayesian approach as multiple imputation methods. Predictive mean matching was used to account for non-normality, where instead of imputing regression estimates, "real" observed values from similar cases are imputed. Methods were also compared by means of a simulated dataset. The simulation showed that the Bayesian approach yielded the most unbiased estimates for imputation. The finding of no increase in consumption levels despite a higher availability remained unaltered. Copyright (C) 2011 John Wiley & Sons, Ltd.

Alcohol MOT part one

The Alcohol MOT is designed to support those working in primary care to carry out alcohol brief interventions. There is extensive evidence to show that primary care-based brief interventions are very effective at reducing drinking at both hazardous and harmful levels. MOT Part 1 enables patients to work out if they are drinking at hazardous or harmful levels. MOT Part 2 helps motivate and support patients to reduce their drinking. Both tools are designed so that a practitioner can work through them with a patient, or a patient can work through them alone.

Alcohol MOT part two

The Alcohol MOT is designed to support those working in primary care to carry out alcohol brief interventions. There is extensive evidence to show that primary care-based brief interventions are very effective at reducing drinking at both hazardous and harmful levels. MOT Part 1 enables patients to work out if they are drinking at hazardous or harmful levels. MOT Part 2 helps motivate and support patients to reduce their drinking. Both tools are designed so that a practitioner can work through them with a patient, or a patient can work through them alone.

Pulmonary tuberculosis: evaluation of interferon-gamma levels as an immunological healing marker based on the response to the Bacillus Calmette-Guerin

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis whose interaction with the host may lead to a cell-mediated protective immune response. The presence of interferon-g (IFN-gamma) is related to this response. With the purpose of understanding the immunological mechanisms involved in this protection, the lymphoproliferative response, IFN-g and other cytokines like interleukin (IL-5, IL-10), and tumor necrosis factor alpha (TNF-a) were evaluated before and after the use of anti-TB drugs on 30 patients with active TB disease, 24 healthy household contacts of active TB patients, with positive purified protein derivative (PPD) skin tests (induration > 10 mm), and 34 asymptomatic individuals with negative PPD skin test results (induration < 5 mm). The positive lymphoproliferative response among peripheral blood mononuclear cells of patients showed high levels of IFN-g, TNF-a, and IL-10. No significant levels of IL-5 were detected. After treatment with rifampicina, isoniazida, and pirazinamida, only the levels of IFN-g increased significantly (p < 0.01). These results highlight the need for further evaluation of IFN-g production as a healing prognostic of patients treated.

A Brief Cognitive Behavioural Therapy Alcohol Intervention Programme is an Effective Secondary Prevention Approach for New Employees entering an Irish Workforce: A Pilot

The prevalence of unhealthy drinking at all levels in Irish society poses serious issues in terms of the consequence to individuals concerned, as well as to society as a whole. The workplace offers a useful setting for early identification and intervention with new employees who may have pre-existing alcohol use disorder issues. This pilot study aimed to evaluate the effectiveness within the workplace of a brief Cognitive Behavioural Therapy (CBT) intervention in reducing participants binge and risky drinking behaviours. Twenty-six Irish Naval recruits volunteered to participate in this randomised controlled trial. The intervention was conducted over four consecutive one and a half hour weekly sessions. Participants completed four principle outcome measures at intake, termination of the intervention and at the two-month follow-up assessment. The Alcohol Use Disorders Identification Test (Babor, Higginis-Biddle, Saunders & Monterio, 2001) was used to measures participants’ consumption levels and frequency of binge or risky drinking. A Readiness Ruler (Miller, Zweben, Diclemente, & Rychtarik, 1992) was used to measure participants’ readiness to change drinking, while the Drinking Expectancy Questionnaire (Young & Oei, 1996) was used to measure participants’ beliefs pertaining to alcohol, and their ability to refuse alcohol in high-risk social surroundings. There were preliminary data in support of the intervention. There were interaction effects that approached statistical significance for both a reduction in participants’ binge drinking (p =. 064) and an increase in participants’ ability to refuse alcohol in high-risk social settings (p = .059). There was also a significant interaction effect (pThis resource was contributed by The National Documentation Centre on Drug Use.

Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels

Background: The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely informative about C(min) exposure. Objectives: The objectives of this study were to improve the interpretation of randomly measured concentrations by using a Bayesian approach for the prediction of C(min), incorporating correlation between pharmacokinetic parameters, and to compare the predictive performance of this method with alternative approaches, by comparing predictions with actual measured trough levels, and with predictions obtained by a reference method, respectively. Methods: A Bayesian maximum a posteriori (MAP) estimation method accounting for correlation (MAP-ρ) between pharmacokinetic parameters was developed on the basis of a population pharmacokinetic model, which was validated on external data. Thirty-one paired random and trough levels, observed in gastrointestinal stromal tumour patients, were then used for the evaluation of the Bayesian MAP-ρ method: individual C(min) predictions, derived from single random observations, were compared with actual measured trough levels for assessment of predictive performance (accuracy and precision). The method was also compared with alternative approaches: classical Bayesian MAP estimation assuming uncorrelated pharmacokinetic parameters, linear extrapolation along the typical elimination constant of imatinib, and non-linear mixed-effects modelling (NONMEM) first-order conditional estimation (FOCE) with interaction. Predictions of all methods were finally compared with 'best-possible' predictions obtained by a reference method (NONMEM FOCE, using both random and trough observations for individual C(min) prediction). Results: The developed Bayesian MAP-ρ method accounting for correlation between pharmacokinetic parameters allowed non-biased prediction of imatinib C(min) with a precision of ±30.7%. This predictive performance was similar for the alternative methods that were applied. The range of relative prediction errors was, however, smallest for the Bayesian MAP-ρ method and largest for the linear extrapolation method. When compared with the reference method, predictive performance was comparable for all methods. The time interval between random and trough sampling did not influence the precision of Bayesian MAP-ρ predictions. Conclusion: Clinical interpretation of randomly measured imatinib plasma concentrations can be assisted by Bayesian TDM. Classical Bayesian MAP estimation can be applied even without consideration of the correlation between pharmacokinetic parameters. Individual C(min) predictions are expected to vary less through Bayesian TDM than linear extrapolation. Bayesian TDM could be developed in the future for other targeted anticancer drugs and for the prediction of other pharmacokinetic parameters that have been correlated with clinical outcomes.

A Study of Tobacco, Alcohol and Drug Use among Irish Female Prisoners

The female prisoner population are a very specific group with very different needs to that of the general population. The study sets out to profile these women and to examine their use of tobacco, alcohol and other substances. A census sample of female prisoners was frequency matched for age with male prisoners and also the female general population. Response rate was 74.6%. Results illustrated that female prisoners are, in the majority from a lower social group, from deprived backgrounds and from families where unemployment is high and education is low. Female prisoners smoke more, take more drugs (including heroin and injection drugs) and drink considerably more when compared to the above groups. They have more alcohol related difficulties as a result of another persons drinking, illustrating high rates of verbal, physical and sexual assault. The prison setting may be the first and possibly the only opportunity for health education and promotion for this particular group. Therefore, with such high reported levels of smoking, alcohol and other substance use, the prison provides a good setting for health promotion interventions.This resource was contributed by The National Documentation Centre on Drug Use.

Travellers and substance use in Ireland: Recommendations for drug and alcohol policy

The Traveller community was traditionally protected from drug use by distinct traditional anti-drug norms and potent family networks within their ‘separateness’ from the ‘settled’ community. Estimations of Traveller substance use remain clouded due to lack of ethnic monitoring in drug reporting systems, and poor service utilization by Travellers. This article draws on a Traveller and substance use regional needs analysis in Ireland, comprising 12 Traveller focus groups and 45 interviews with key stakeholders. Drug activity in terms of both drug dealing and drug use among Travellers is increasing in recent years [Van Hout, M.C. (2009a). Substance misuse in the traveller community: A regional needs assessment. Western Regional Drug Task Force. Series 2. ISBN 978-0-9561479-2-9].   Traditional resiliency factors are dissipating in strength due to increased Traveller housing within marginalized areas experiencing drug activity and increased levels of young Travellers encountering youth drug use within school settings, by way of their attempts ‘to fit in’ and integrate with their ‘settled peers’ [Van Hout, M.C. (2009b). Irish travellers and drug use – An exploratory study. Ethnicity and Inequalities in Health and Social Care, 2(1), 42–49]. Fragmentation of Traveller culture is occurring as Travellers strive to retain their identity within the assimilation process into modern sedentarist Irish society. Treatment and outreach policies need to protect Traveller identity by reducing discriminatory experiences, promoting cultural acceptance with service staff and addressing literacy, implementing peer led approaches and offering flexible therapy modalities.This resource was contributed by The National Documentation Centre on Drug Use.

Effectiveness of brief alcohol interventions in primary care populations.

Excessive drinking contributes significantly to social problems, physical and psychological illness, injury and death. Hidden effects include increased levels of violence, accidents and suicide. Most alcohol-related harm is caused by excessive drinkers whose consumption exceeds recommended drinking levels, not the drinkers with severe alcohol dependency problems. One way to reduce consumption levels in a community may be to provide a brief intervention in primary care over one to four sessions. This is provided by healthcare workers such as general physicians, nurses or psychologists. In general practice, patients are routinely asked about alcohol consumption during registration, general health checks and as part of health screening (using a questionnaire). They tend not to be seeking help for alcohol problems when presenting. The intervention they are offered includes feedback on alcohol use and harms, identification of high risk situations for drinking and coping strategies, increased motivation and the development of a personal plan to reduce drinking. It takes place within the time-frame of a standard consultation, 5 to 15 minutes for a general physician, longer for a nurse.A total of 29 controlled trials from various countries were identified, in general practice (24 trials) or an emergency setting (five trials). Participants drank an average of 306 grams of alcohol (over 30 standard drinks) per week on entry to the trial. Over 7000 participants with a mean age of 43 years were randomised to receive a brief intervention or a control intervention, including assessment only. After one year or more, people who received the brief intervention drank less alcohol than people in the control group (average difference 38 grams/week, range 23 to 54 grams). For men (some 70% of participants), the benefit of brief intervention was a difference of 57 grams/week, range 25 to 89 grams (six trials). The benefit was not clear for women. The benefits of brief intervention were similar in the normal clinical setting and in research settings with greater resources. Longer counselling had little additional benefit.This resource was contributed by The National Documentation Centre on Drug Use.

National Alcohol Policy Ireland

The National Alcohol Policy is directed at reducing the prevalence of alcohol-related problems through an emphasis on moderation in alcohol consumption. The importance of a comprehensive alcohol policy was highlighted when Ireland endorsed the European Charter on Alcohol in December 1995 along with 48 other Member States of the WHO European Region. The alcohol-related problems are multidimensional, therefore the solutions most be multi-sectoral. This means that commitment to the National Alcohol Policy must be on the agenda of policy makers in all sectors and at all levels. An Alcohol Policy requires both environmental and individual strategies. There is strong evidence that policies which influence access to alcohol, control pricing through taxation and other public health measures, can have a positive impact on curtailing the health and social burden resulting from drinking (Edwards et al. 1994). However, a key to the effectiveness of such strategies is public support, enforcement and maintenance of the policies. In examining the rationale for a National Alcohol Policy a number of elements have been identified. Research is urgently required to identify attitudes and patterns of alcohol consumption across the population and within sub-groups of the population. Based on sound research, a sensible drinking message of Less is Better should form an educational empowerment programme with regional and local initiatives as a required and integral part of such a campaign. A health education programme in all schools should be part of the core curriculum. The availability and effectiveness of treatment services need to be established. Action to contain the availability of alcohol could be achieved by reducing the number of special exemptions for longer opening hours and controlling access to underage drinking by ID schemes nation-wide. The enforcement of drink driving legislation including random breath testing needs to be continued to reduce alcohol-related traffic accidents. All levels of the Drinks Industry should recognise that people have the right to be safeguarded from pressures to drink. Finally, a National Alcohol Policy could be co-ordinated by a wider National Substance Use Surveillance Unit.This resource was contributed by The National Documentation Centre on Drug Use.

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro, Brazil

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8% females and 62.2% males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had ³ 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85%), a number of 28.5% showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.

Alcohol MOT part two

The Alcohol MOT is designed to support those working in primary care to carry out alcohol brief interventions. There is extensive evidence to show that primary care-based brief interventions are very effective at reducing drinking at both hazardous and harmful levels. MOT Part 1 enables patients to work out if they are drinking at hazardous or harmful levels. MOT Part 2 helps motivate and support patients to reduce their drinking. Both tools are designed so that a practitioner can work through them with a patient, or a patient can work through them alone.

Alcohol MOT part one

The Alcohol MOT is designed to support those working in primary care to carry out alcohol brief interventions. There is extensive evidence to show that primary care-based brief interventions are very effective at reducing drinking at both hazardous and harmful levels. MOT Part 1 enables patients to work out if they are drinking at hazardous or harmful levels. MOT Part 2 helps motivate and support patients to reduce their drinking. Both tools are designed so that a practitioner can work through them with a patient, or a patient can work through them alone.