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Background: Common to most theory-based intervention approaches is the idea of supporting intentions to increase the probability of behavior change. This principle works only if (a) intentions can be explained by the hypothesized socio-cognitive constructs, and (b) people actually do what they intend to do. The overall aim of this thesis was to test these premises using two health behavior theories applied to reducing at-risk alcohol use. Method: The three papers underlying this thesis were based on data of the randomized controlled “Trial Of Proactive Alcohol interventions among job-Seekers” (TOPAS). A total of 1243 job-seekers with at-risk alcohol use were randomized to stage tailored intervention (ST), non-stage tailored intervention (NST), or control group. The ST participants (n = 426) were analyzed in paper 1. Paper 2 was based on the baseline and 3-month data provided by the NST participants (n = 433). Paper 3 was based on baseline, 3-, 6-, and 15-month data provided by the control and ST group not intending to change alcohol use (n = 629). Latent variable modeling was used to investigate the associations of social-cognitive constructs and intentional stages (paper 1), the extent to which intentions were translated into alcohol use (paper 2), and the different trajectories of alcohol use among people not intending to change as well as the ST effect on the trajectories (paper 3). Results: Persons in different intentional stages differed in the processes of change in which they engaged, in the importance placed by them on the pros and cons of alcohol use, and in the perceived ability to quit (ps < 0.01). The association between intentions and alcohol use was weak. The magnitude of this intention-behavior gap depended on the extent to which normative expectations have changed over time (p < 0.01) and was reduced when controlling for the mediating effect of temporal stability of intentions. The gap was also present among people not intending to change: Even without intervention, 35% of the persons reduced the amount of alcohol use after 15 months (p < 0.05) and 2% achieved abstinence. Persons with heavier drinking (33%) and persons with low but frequent use (30%) did not change. Persons with frequent alcohol use seem to benefit less from ST than those with occasional use, although differences were not statistically significant. Conclusions: Intentions can be quite well explained by the hypothesized socio-cognitive constructs. In a sample of persons who were, as a whole, little motivated to change, the precision of how well intentions predict subsequent alcohol use was modest though. Time and socio-contextual influences should be considered.
Alcohol-related somatic disorders are highly prevalent among general hospital inpatients. Alcohol problem drinking can be differentiated into alcohol use disorders (alcohol dependence and alcohol abuse) and three subtypes of drinking above recommended levels (at-risk drinking only [AR], heavy episodic drinking only [HE], at-risk and heavy episodic drinking [ARHE]). The aims of this study were threefold. First, proportions of alcohol problem drinking among general hospital inpatients in a region of north-eastern Germany were estimated (study 1). Second, among individuals with alcohol problem drinking the association between beverage preference and alcohol-related diseases was tested (study 2). Third, subtype differences regarding demographics, alcohol-related variables, motivation to change drinking behaviors, and the risk to develop short-term alcohol dependence among the three subtypes of drinking above recommended levels were analyzed (study 3). The data presented in this dissertation are based on the randomized controlled trial “Early Intervention at General Hospitals”, which is part of the Research Collaboration Early Substance Use Intervention (EARLINT). Study 1 includes a sample of consecutively admitted general hospital inpatients between 18 and 64 years old (n = 14,332). The study adopted a two-stage-sampling approach: (a) screening and (b) ascertainment of alcohol problem drinking. Those who were identified with alcohol problem drinking were asked for written consent for further study participation. This included further baseline assessment, the consent to use routine treatment diagnoses and participation in a follow-up interview 12 months after hospitalization. For study 2, routine treatment diagnoses were provided by hospital physicians for a total of 1,011 men with problem drinking. These diagnoses were classified into three categories according to their alcohol-attributable fractions (AAF): diseases totally attributable to alcohol by definition (AAF=1), diseases partially attributable to alcohol (AAF<1) and diseases with no empirical relationship to alcohol or with a possibly protective effect associated with alcohol (AAF=0). Study 3 was restricted to study participants with drinking above recommended levels (n=425). Study 1: Among all general hospital inpatients, 8.9% were identified with current problem drinking in the following descending order: 5.3% exhibited alcohol use disorders and 3.6% drinking above recommended levels. Higher proportions of problem drinking were found at rural sites compared to urban sites (13.7 vs. 7.5%, p<.001). Study 2: Because of the low proportion of women with alcohol problem drinking the following analyses were restricted to males. Multinomial regression analyses revealed different risks for alcohol-related diseases in relation to beverage preference while controlling for alcohol-associated and demographic confounders. Compared to all other groups, spirits only drinkers had the highest risk for having a disease with AAF>0; e.g., beer only drinkers had lower odds of having a disease with AAF<1 (odds ratio, OR=0.50, 95% confidence interval, CI: 0.27-0.92). Study 3: Men with alcohol use disorder were excluded from the following analysis. At baseline, multinomial logistic regression revealed differences between individuals with AR, HE and ARHE while controlling for age. ARHE was associated with higher odds of having a more severe alcohol problem (OR=2.06, CI: 1.23-3.45), using formal help (OR=2.21, CI: 1.02-4.79), and having a disease with AAF=1 (OR=3.43, CI: 1.58-7.43), compared with AR. In addition, individuals with ARHE had higher odds of taking action to change drinking behaviors (i.e., beginning to implement change) than individuals with HE (OR=2.29, CI: 1.21-4.34) or AR (OR=2.11, CI: 1.15-3.86). At follow-up, individuals with ARHE had higher odds of having alcohol dependence according to the DSM-IV (OR=4.73, CI: 1.01–22.20) compared to individuals with AR. In addition to alcohol use disorders, drinking above recommended levels is a common problem among general hospital inpatients. Thus, the implementation of systematic alcohol screening and brief interventions should be considered. These data suggest an association between beverage preference and alcohol-related diseases. Among hospitalized problem drinkers, spirits only drinkers had the greatest risk of having diseases with AAF>0. Of the three subtypes of drinking above recommended levels, ARHE seems to be particularly problematic because there appears to be an indication of a subclinical diagnosis. To provide adequate intervention, clinical practice should distinguish between the three groups of drinking above recommended levels. Brief alcohol intervention should be tailored to the individual’s motivation to change and to the type of alcohol problem drinking. The effectiveness of such a procedure remains to be evaluated in further studies.
Tertiary alcohols have become interesting targets for organic synthesis themselves or as building blocks for valuable pharmaceutical compounds. However, the synthesis of optically pure tertiary alcohols is still a challenge both chemical and enzymatic means. Enzymes containing the GGG(A)X motif in the active site region have been known to show activity towards these sterically demanding substrates. Several tertiary alcohols have been resolved with high enantioselectivity by using this biocatalytic synthetic route. This thesis aims at providing a better understanding of enantiorecognition of GGG(A)X motif hydrolases in the enzymatic synthesis of enantiomerically enriched tertiary alcohols. Kinetic resolution of a wide range of tertiary alcohols using hydrolases provided insights on factors that can influence enantioselectivity of GGG(A)X motif enzymes. Additionally, a newly proposed chemoenzymatic method to synthesize protected alpha,alpha-dialkyl-alpha-hydroxycarboxylic acids has broadened the application of these enzymes to synthesize optically pure tertiary alcohols. Newly found biocatalysts through functional screening, database mining and rational protein design approaches provided a better enzyme platform for optically pure tertiary alcohol resolution.
Background: To reduce the burden of disease attributable to alcohol, screening for at-risk alcohol use in the general population is recommended. Screening is usually carried out at only one point in time although individual alcohol use may change over time and self-reported consumption may be biased by underreporting. However, there are gaps in research on temporal variability of alcohol use. Therefore, this cumulative dissertation investigated (1) changes in drinking patterns within 4 weeks; (2) changes in screening results within 12 months and factors predicting a transition from low-risk to at-risk alcohol use; (3) whether underreporting can be reduced by prompting respondents to recall their alcohol use in the past week prior to screening.
Methods: Participants were adults from the general population recruited in a municipal registry office. For the first paper, 288 alcohol users were assessed four times using Timeline Follow-Back, each one week apart. Changes in drinking patterns were analyzed using latent transition modeling. For the second paper, 831 control group participants of a randomized controlled trial were screened for at-risk alcohol use at baseline, 3, 6, and 12 months later using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C). The transition from low-risk to at-risk alcohol use was predicted using logistic regression. For the third paper, 2,379 alcohol users were screened for at-risk alcohol use using the AUDIT-C, either before or after receiving the prompt to recall their past week alcohol use. Data were analyzed using logistic regression.
Results: Within 4 weeks, 35 percent of alcohol users changed their drinking pattern. Changes were more likely for individuals with moderate or heavy compared to light drinking. Within 12 months, 30 percent of alcohol users changed their screening result. Changes were more likely for at-risk compared to low-risk alcohol users. Transitioning from low-risk to at-risk alcohol use was more likely for women (vs. men; Odds Ratio, OR = 1.66), 18- to 29-year-old adults (vs. 30- to 45-year-old adults; OR = 2.30), and individuals reporting two or more drinking days in the past week (vs. less than two; OR = 3.11). When respondents were prompted to recall their alcohol use in the past week prior to screening, they were less likely to report at-risk alcohol use compared to when the screening was conducted without prior prompt (OR = 0.83).
Conclusions: One in three alcohol users changed their consumption, some of them even within a period as short as 4 weeks. These changes might compromise the validity of screening that is commonly based on a single assessment of typical alcohol use. Furthermore, underreporting cannot be reduced by prompting individuals to recall their alcohol use in the past week prior to the screening for at-risk alcohol use. Rather, consecutive questionnaires addressing different aspects of alcohol use within a single survey might be a potential source of bias.