Acute alcohol consumption and mechanism of injury

Objective: The purpose of this study was to determine whether injury mechanism among injured patients is differentially distributed as a function of acute alcohol consumption (quantity, type, and drinking setting). Method: A cross-sectional study was conducted between October 2000 and October 2001 in the Gold Coast Hospital Emergency Department, Queensland, Australia. Data were collected quarterly over a 12-month period. Every injured patient who presented to the emergency department during the study period for treatment of an injury sustained less than 24 hours prior to presentation was approached for interview. The final sample comprised 593 injured patients (males = 377). Three measures of alcohol consumption in the 6 hours prior to injury were obtained from self-report: quantity, beverage type, and drinking setting. The main outcome measure was mechanism of injury which was categorized into six groups: road traffic crash (RTC), being hit by or against something, fall, cut/piercing, overdose/poisoning, and miscellaneous. Injury intent was also measured (intentional vs unintentional). Results: After controlling for relevant confounding variables, neither quantity nor type of alcohol was significantly associated with injury mechanism. However, drinking setting (i.e., licensed premise) was significantly associated with increased odds of sustaining an intentional versus unintentional injury (odds ratio [OR] = 2.79, 95% confidence interval [CI] = 1.4-5.6); injury through being hit by/against something versus other injury types (OR = 2.59, 95% CI = 1.4-4.9); and reduced odds of sustaining an injury through RTC versus non-RTC (OR = 0.02, 95% CI = 0.004-0.9), compared with not drinking alcohol prior to injury. Conclusions: No previous analytical studies have examined the relationship between injury mechanism and acute alcohol consumption (quantity, type, and setting) across all types of injury and all injury severities while controlling for potentially important confounders (demographic and situational confounders, risk-taking behavior, substance use, and usual drinking patterns). These data suggest that among injured patients, mechanism of injury is not differentially distributed as a function of quantity or type of acute alcohol consumption but may be differentially distributed as a function of drinking setting (i.e., RTC, intentional injury, being hit). Therefore, prevention strategies that focus primarily on the quantity and type of alcohol consumed should be directed generically across injury mechanisms and not limited to particular cause of injury campaigns.

Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: A meta-analysis of individual patient data

Background & Aims: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. Methods: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. Results: Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in :1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in :142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. Conclusions: In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.

Subtypes of Illicit Drug Users: A Latent Class Analysis of Data From an Australian Twin Sample

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

ANSIEDADE E CONSUMO DE SUBSTÂNCIAS PSICOATIVAS EM ADOLESCENTES

Os objetivos deste estudo foram: relacionar o consumo de substâncias psicoativas e ansiedade, verificar os níveis de ansiedade e as substâncias psicoativas mais consumidas, e associar consumo de substâncias psicoativas e ansiedade entre estudantes do ensino médio de escolas públicas e particulares da cidade de Maceió. Os estudantes e as instituições que participaram da pesquisa foram selecionados por meio de amostragem não-probabilística por conveniência. Tratou-se de um estudo de delineamento correlacional. A amostra foi de 407 estudantes, com idade de 14 a 18 anos. A pesquisa foi realizada em sete escolas, sendo quatro da rede pública estadual e três da rede particular. Os participantes responderam a um questionário sóciodemográfico; à Escala de Ansiedade do Adolescente (EAA); e a um questionário sobre o consumo de substâncias psicoativas. Foi feita a análise das relações entre consumo de substâncias psicoativas e ansiedade por meio do teste qui-quadrado e exato de Fisher. O álcool foi a substância lícita mais consumida pelos estudantes, enquanto o solvente, a substância ilícita mais consumida por esse grupo. Os participantes apresentaram maior percentual no nível moderado: 28%. Verificou-se diferença estatisticamente significativa entre o consumo de substâncias psicoativas e ansiedade nos adolescentes. O uso na vida de solventes (p=0,037) e energéticos (p=0,023); uso no ano de cigarro (p=0,043) e bebidas alcoólicas (p=0,007); e uso freqüente de bebidas alcoólicas (p<0,001) relacionou-se com ansiedade moderada. Houve diferença significativa entre consumo de substâncias psicoativas e ansiedade nos tipos de escola: Na escola pública, houve relação entre estudantes que disseram consumir cigarro na vida e no ano, e entre os que fizeram uso na vida de solventes e energéticos com ansiedade grave (p=0,022; p=0,003; p=0,010;p=0=0,44, respectivamente); e entre estudantes que afirmaram ter feito consumo freqüente de bebidas alcoólicas com ansiedade moderada (p=0,007). Na escola particular, houve relação entre estudantes consumiram bebidas alcoólicas no ano com ansiedade moderada (p=0,011). A pesquisa verificou a necessidade de se realizarem projetos de prevenção de drogas e promoção de saúde que visem aumentar a reflexão sobre o estilo de vida e ansiedade.

Ideological Closure : Drug Prevention in a Post-political Society

The aim of this thesis is to critically examine drug prevention as a field of problematizations  – how drug prevention becomes established as a political technology within this field, how it connects to certain modes of governance, how and under which conditions it constitutes it’s problematic, the questions it asks,  it´s implications in terms of political participation and representation, the various bodies of knowledge through which it constitutes the reality upon which it acts, the limits it places on ways of being, questioning, and talking  in the world. The main analyses have been conducted in four separate but interrelated articles. Each article addresses a specific dimension of drug prevention in order to get a grasp of how this field is organized. Article 1 examines the shift that has occurred in the Swedish context during the period 1981–2011 in how drugs have been problematized, what knowledge has grounded the specific modes of problematization and which modes of governance this has enabled. In article 2, the currently dominant scientific discipline in the field of drug prevention – prevention science – is critically examined in terms of how it constructs the “drug problem” and the underlying assumptions it carries in regard to reality and political governance. Article 3 addresses the issue of communities’ democratic participation in drug prevention efforts by analyzing the theoretical foundations of the Communities That Care prevention program. The article seeks to uncover how notions of community empowerment and democratic participation are constructed, and how the “community” is established as a political entity in the program. The fourth and final article critically examines the Swedish Social and Emotional Training (SET) program and the political implications of the relationship the program establishes between the subject and emotions. The argument is made that, within the field of drug prevention, questions of political values and priorities in a problematic way are decoupled from the political field and pose a significant problem in terms of the possibilities to engage in democratic deliberation. Within this field of problematizations it becomes impossible to mobilize a politics against social injustice, poverty and inequality. At the same time, the scientific grounding of this mode of governing the drug “problem” acts to naturalize a specific – highly political – way of engaging with drugs.

Towards an improved ocular drug delivery system

The ultimate aim of this project was to design new biomaterials which will improve the efficiency of ocular drug delivery systems. Initially, it was necessary to review the information available on the nature of the tear fluid and its relationship with the eye. An extensive survey of the relevant literature was made. There is a common belief in the literature that the ocular glycoprotein, mucin, plays an important role in tear film stability, and furthermore, that it exists as an adherent layer covering the corneal surface. If this belief is true, the muco-corneal interaction provides the ideal basis for the development of sustained release drug delivery. Preliminary investigations were made to assess the ability of mucin to adhere to polymer surfaces. The intention was to develop a synthetic model which would mimic the supposed corneal/mucin interaction. Analytical procedures included the use of microscopy (phase contrast and fluorescence), fluorophotometry, and mucin-staining dyes. Additionally, the physical properties of tears and tear models were assessed under conditions mimicking those of the preocular environment, using rheological and tensiometric techniques. The wetting abilities of these tear models and opthalmic formulations were also investigated. Tissue culture techniques were employed to enable the surface properties of the corneal surface to be studied by means of cultured corneal cells. The results of these investigations enabled the calculation of interfacial and surface characteristics of tears, tear models, and the corneal surface. Over all, this work cast doubt on the accepted relationship of mucin with the cornea. A corneal surface model was designed, on the basis of the information obtained during this project, which would possess similar surface chemical properties (i.e. would be biomimetic) to the more complex original. This model, together with the information gained on the properties of tears and solutions intended for ocular instillation, could be valuable in the design of drug formulations with enhanced ocular retention times. Furthermore, the model itself may form the basis for the design of an effective drug-carrier.

Investigating the modulation of oral drug absorption using in vitro models

Dipeptides can be absorbed into cells via the dipeptide transporter (which also transported tripeptides and dipeptide derivatives). The optimum conditions for measuring the inhibition of Gly-Pro uptake in Caco-2 cells were identified. A number of structure-activity relationships were identified. These included the effects of increasing the amino-acid chain-length, and the presence of a thiol or hydroxyl group in the side-chain increased IC50 while the presence of a hydroxyl group did not. The benzyl esters had lower or equal IC50 values compared to the parent dipeptides while the methyl esters had higher values. These results indicated that while molecular properties did affect IC50, the size, charge and composition of three particular groups caused the most significant effects, supporting the structure-activity relationship identified. An assay was developed using calcein-AM to show the inhibition of p-glycoprotein activity. There was no significant change due to the presence of mannitol but there was in the presence of clyclosporin A (p<0.01). Incubating the cells with the test solution for 30 minutes before the addition of the ester resulted in a significant (p<0.001) difference. The assay was specific for p-glycoprotein, as the presence MRP inhibitors had no effect (p>0.05). The modified protocol allowed the identification of p-glycoprotein inhibitors quickly and simply using a cell suspension of unmodified cells. The clinically relevant buffering of grapefruit juice to pH 7 led to a four-fold increase in intracellular calcein and hence significant inhibition of p-glycoprotein. Buffered orange and lemon juices had no effect on the assay. Flavone derivatives had previously been found to be inhibitors of CYP3A4 yet neither naringin nor naringenin had any significant effect at concentrations found in grapefruit juice. Of the other (non-grapefruit) flavone derivatives tested, hesperidin, found in orange juice, had no significant effect, kaempferol and rutin also had no effect while genistein significantly inhibited p-glycoprotein (results that support previous studies). Hydroxycinnamic acids had no effect on p-glycoprotein. Studies on other compounds found that the balance between inhibiting p-glycoprotein and disrupting cell membranes depends on the compound containing an oxygen atom and the size of the negative charge on it, as well as three-dimensional arrangement of the atoms.

Drug information in general practice pharmacy

The drug information sources currently available to general practice pharmacists have been identified. The use of and attitudes to these sources were assessed as well as the perceived information needs of practising pharmacists. The special requirements of women pharmacists and pharmacists working part-time were studied. The relationship of the medical representative as an information source for pharmacists was evaluated. Participation in continuing education programmes as a vital means of ensuring current information awareness and knowledge for the practising profession has been considered. Investigations were mainly pursued by questionnaire survey, while computer facilities were used for the processing and the analyses of data. The desirability of collated and evaluated information from one or more independent authoritative sources has been discussed. The increasing advisory role of the general practice pharmacist and the needs of the patient and potential customer have been discussed, with projections for the pharmacist's future health care contribution.

A demonstration of attentional bias, using a novel dual task paradigm, towards clinically salient material in recovering alcohol abuse patients?

Background. This study examined whether alcohol abuse patients are characterized either by enhanced schematic processing of alcohol related cues or by an attentional bias towards the processing of alcohol cues. Method. Abstinent alcohol abusers (N = 25) and non-clinical control participants (N = 24) performed a dual task paradigm in which they had to make an odd/even decision to a centrally presented number while performing a peripherally presented lexical decision task. Stimuli on the lexical decision task comprised alcohol words, neutral words and non-words. In addition, participants completed an incidental recall task for the words presented in the lexical decision task. Results. It was found that, in the presence of alcohol related words, the performance of patients on the odd/even decision task was poorer than in the presence of other stimului. In addition, patients displayed slower lexical decision times for alcohol related words. Both groups displayed better recall for alcohol words than for other stimuli. Conclusions. These results are interpreted as supporting neither model of drug cravings. Rather, it is proposed that, in the presence of alcohol stimuli, alcohol abuse patients display a breakdown in the ability to focus attention.

How well does the theory of planned behaviour predict alcohol consumption? A systematic review and meta-analysis

This study aimed to quantify correlations between theory of planned behaviour (TPB) variables and (i) intentions to consume alcohol and (ii) alcohol consumption. Systematic literature searches identified 40 eligible studies that were meta-analysed. Three moderator analyses were conducted: pattern of consumption, gender of participants and age of participants. Across studies, intentions had the strongest relationship with attitudes (r+ = .62), followed by subjective norms (r+ = .47) and perceived behavioural control (PBC; r+ = .31). Self-efficacy (SE) had a stronger relationship with intentions (r+ = .48) compared with perceived control (PC; r+ = −.10). Intention had the strongest relationship with alcohol consumption (r+ = .54), followed by SE (r+ = .41). In contrast, PBC and PC had negative relationships with alcohol consumption (r+ = −.05 and −.13, respectively). All moderators affected TPB relationships. Patterns of consumption with clear definitions had stronger TPB relations, females reported stronger attitude–intention relations than males, and adults reported stronger attitude–intention and SE–intention relations than adolescents. Recommendations for future research include targeting attitudes and intentions in interventions to reduce alcohol consumption, using clear definitions of alcohol consumption in TPB items to improve prediction and assessing SE when investigating risk behaviours.

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

Primary objective: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. Research design: A retrospective case note review assessed total rehabilitation unit admission. Methods and procedures: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. Main outcomes and results: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = −6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36–68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002–0.35). Conclusions: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort.

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Optimization Problem in a Class of Linear System. Application to Multiple Drug Administration

2000 Mathematics Subject Classification: 62H15, 62P10.