Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation

Mechanisms of action of brief alcohol interventions remain largely unknown - a narrative review.

A growing body of evidence has shown the efficacy of brief intervention (BI) for hazardous and harmful alcohol use in primary health care settings. Evidence for efficacy in other settings and effectiveness when implemented at larger scale are disappointing. Indeed, BI comprises varying content; exploring BI content and mechanisms of action may be a promising way to enhance efficacy and effectiveness. Medline and PsychInfo, as well as references of retrieved publications were searched for original research or review on active ingredients (components or mechanisms) of face-to-face BIs [and its subtypes, including brief advice and brief motivational interviewing (BMI)] for alcohol. Overall, BI active ingredients have been scarcely investigated, almost only within BMI, and mostly among patients in the emergency room, young adults, and US college students. This body of research has shown that personalized feedback may be an effective component; specific MI techniques showed mixed findings; decisional balance findings tended to suggest a potential detrimental effect; while change plan exercises, advice to reduce or stop drinking, presenting alternative change options, and moderation strategies are promising but need further study. Client change talk is a potential mediator of BMI effects; change in norm perceptions and enhanced discrepancy between current behavior and broader life goals and values have received preliminary support; readiness to change was only partially supported as a mediator; while enhanced awareness of drinking, perceived risks/benefits of alcohol use, alcohol treatment seeking, and self-efficacy were seldom studied and have as yet found no significant support as such. Research is obviously limited and has provided no clear and consistent evidence on the mechanisms of alcohol BI. How BI achieves the effects seen in randomized trials remains mostly unknown and should be investigated to inform the development of more effective interventions

Effects of study design and allocation on self-reported alcohol consumption: randomized trial.

BACKGROUND: What participants think about the nature of a study might affect their behaviour and bias findings. We tested two hypotheses: (1) participants told they were in an intervention trial would report lower alcohol consumption at follow-up than those told they were in a cohort study; (2) participants told they were in the intervention group in a trial would have lower alcohol consumption at follow-up than those told they were in the control group. METHODS: Students from four universities (N = 72,903) were invited to participate in a 'research project on student drinking'. Of 10,415 respondents, 6,788 were moderate to heavy drinkers and were randomized. Group A ('cohort') were informed their drinking would be assessed at baseline and again in one month. Group B ('control') were told the study was an intervention trial and they were in the control group. Group C ('intervention') were told the study was an intervention trial and they were to receive the intervention. All were assessed and directed to read identical online alcohol education material. Whether and how long they accessed the material were recorded. One month later, alcohol intake was reassessed. RESULTS: In relation to hypothesis 1, there were no differences between the groups on the prespecified outcome measures. In relation to hypothesis 2, there were no differences though all point estimates were in the hypothesized direction (that is, 'intervention' < 'control'). The 'cohort' and 'control' groups accessed the material to a similar extent (59% versus 57%) while the 'intervention' group were more likely to access it (78%) and to read it for longer (median 35 s (25th and 75th percentiles: 6, 97) versus medians of 7 s (0, 28) and 8 s (4, 42) for the 'cohort' and 'control' groups, respectively). CONCLUSIONS: Although the context given to the research participants significantly influenced access to the online information and reading time, this did not translate into any effect on drinking behaviour, for either hypothesis. This might be because of failure in the experimental paradigm or the possibility of weaker effects using the online approach. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000846022

Web-based alcohol screening and brief intervention for university students: a randomized trial.

IMPORTANCE: Unhealthy alcohol use is a leading contributor to the global burden of disease, particularly among young people. Systematic reviews suggest efficacy of web-based alcohol screening and brief intervention and call for effectiveness trials in settings where it could be sustainably delivered. OBJECTIVE: To evaluate a national web-based alcohol screening and brief intervention program. DESIGN, SETTING, AND PARTICIPANTS: A multisite, double-blind, parallel-group, individually randomized trial was conducted at 7 New Zealand universities. In April and May of 2010, invitations containing hyperlinks to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening test were e-mailed to 14,991 students aged 17 to 24 years. INTERVENTIONS: Participants who screened positive (AUDIT-C score ≥4) were randomized to undergo screening alone or to 10 minutes of assessment and feedback (including comparisons with medical guidelines and peer norms) on alcohol expenditure, peak blood alcohol concentration, alcohol dependence, and access to help and information. MAIN OUTCOMES AND MEASURES: A fully automated 5-month follow-up assessment was conducted that measured 6 primary outcomes: consumption per typical occasion, drinking frequency, volume of alcohol consumed, an academic problems score, and whether participants exceeded medical guidelines for acute harm (binge drinking) and chronic harm (heavy drinking). A Bonferroni-corrected significance threshold of .0083 was used to account for the 6 comparisons and a sensitivity analysis was used to assess possible attrition bias. RESULTS: Of 5135 students screened, 3422 scored 4 or greater and were randomized, and 83% were followed up. There was a significant effect on 1 of the 6 prespecified outcomes. Relative to control participants, those who received intervention consumed less alcohol per typical drinking occasion (median 4 drinks [interquartile range {IQR}, 2-8] vs 5 drinks [IQR 2-8]; rate ratio [RR], 0.93 [99.17% CI, 0.86-1.00]; P = .005) but not less often (RR, 0.95 [99.17% CI, 0.88-1.03]; P = .08) or less overall (RR, 0.95 [99.17% CI, 0.81-1.10]; P = .33). Academic problem scores were not lower (RR, 0.91 [99.17% CI, 0.76-1.08]; P = .14) and effects on the risks of binge drinking (odds ratio [OR], 0.84 [99.17% CI, 0.67-1.05]; P = .04) and heavy drinking (OR, 0.77 [99.17% CI, 0.56-1.05]; P = .03) were not significantly significant. In a sensitivity analysis accounting for attrition, the effect on alcohol per typical drinking occasion was no longer statistically significant. CONCLUSIONS AND RELEVANCE: A national web-based alcohol screening and brief intervention program produced no significant reductions in the frequency or overall volume of drinking or academic problems. There remains a possibility of a small reduction in the amount of alcohol consumed per typical drinking occasion. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000279022

Do type I collagen defects that cause Osteogenesis Imperfecta result in an inherent muscle pathology? [abstract]

Abstract only availableOsteogenesis imperfecta (OI) is a congenital connective tissue disorder characterized by decreased bone mineral density and increased bone fragility and susceptibility to fracture. In addition to skeletal fragility, patients with OI reportedly have muscle weakness, although currently no systematic evaluation of muscle function or morphology in humans or animal models of the disease has been performed. Normal type I collagen is coded for by two genes located on different chromosomes: COL1A1 and COL1A2. The oim/oim mouse is homozygous for a null mutation in the COL1A2 gene and is a phenocopy of a human type III OI (severe disease phenotype). Heterozygous mice (oim/+) harbor the null mutation in only one allele of the COL1A2 gene and model human patients with type I OI (mild disease phenotype). One of our aims is to characterize and determine muscle mass and cross-sectional area of hind limb muscle fibers in wild type (+/+), heterozygous (oim/+), and homozygous (oim/oim) mice. We analyzed muscle mass, fiber morphology, cross-sectional area of hindlimb muscles, as well as fiber type composition of the soleus muscle of oim, oim/+ relative to +/+ mouse muscles and determined that significant differences do not exist between genotypes. We also determined that there is no evidence of necrosis, degeneration, regeneration, hypertrophy or atrophy in hindlimb muscles of oim/oim and oim/+ mice. We correlated our morphologic findings with a functional contractile assay and determined that muscle tension-force generation and nerve conduction are not impaired in oim mice. These findings suggest that oim and oim/+ mice do not have inherent muscle pathology. This knowledge is important in our ultimate understanding of skeletal muscle in OI model mice and ultimately, humans with this disease.Biochemistry Departmen

Web-based alcohol intervention for Māori university students: double-blind, multi-site randomized controlled trial.

AIMS: Like many indigenous peoples, New Zealand Māori bear a heavy burden of alcohol-related harm relative to their non-indigenous compatriots, and disparities are greatest among young adults. We tested the effectiveness of web-based alcohol screening and brief intervention (e-SBI) for reducing hazardous drinking among Māori university students. DESIGN: Parallel, double-blind, multi-site, randomized controlled trial. SETTING: Seven of New Zealand's eight universities. PARTICIPANTS: In April 2010, we sent e-mail invitations to all 6697 17-24-year-old Māori students to complete a brief web questionnaire including the Alcohol Use Disorders Identification Test (AUDIT)-C, a screening tool for hazardous and harmful drinking. Those screening positive were computer randomized to: <10 minutes of web-based alcohol assessment and personalized feedback (intervention) or screening alone (control). MEASUREMENTS: We conducted a fully automated 5-month follow-up assessment with observers and participants blinded to study hypotheses, design and intervention delivery. Pre-determined primary outcomes were: (i) frequency of drinking, (ii) amount consumed per typical drinking occasion, (iii) overall volume of alcohol consumed and (iv) academic problems. FINDINGS: Of the participants, 1789 were hazardous or harmful drinkers (AUDIT-C ≥ 4) and were randomized: 850 to control, 939 to intervention. Follow-up assessments were completed by 682 controls (80%) and 733 intervention group members (78%). Relative to controls, participants receiving intervention drank less often [RR = 0.89; 95% confidence interval (CI): 0.82-0.97], less per drinking occasion (RR = 0.92; 95% CI: 0.84-1.00), less overall (RR = 0.78; 95% CI: 0.69-0.89) and had fewer academic problems (RR = 0.81; 95% CI: 0.69-0.95). CONCLUSIONS: Web-based screening and brief intervention reduced hazardous and harmful drinking among non-help-seeking Māori students in a large-scale pragmatic trial. The study has wider implications for behavioural intervention in the important but neglected area of indigenous health

Characterization of muscle in OI Model mice

Abstract only availableOsteogenesis imperfecta (OI) is a congenital connective tissue disorder characterized by decreased bone mineral density and increased bone fragility and susceptibility to fracture. In addition to skeletal fragility, patients with OI reportedly have muscle weakness although currently no systematic evaluation of muscle function or morphology in humans or animal models of the disease has been performed. Normal type I collagen is coded for two genes located on different chromosomes: COL1A1 and COL1A2. The oim/oim mouse is homozygous for a null mutation in the COL1A2 gene and is a phenocopy of human type III OI (severe disease phenotype). Heterozygous mice (oim/+) harbor the null mutation in only one allele of the COL1A2 gene and model human patients with type I OI (mild disease phenotype). We wanted to determine whether the reported muscle weakness in OI patients is due to a muscle pathology. We analyzed the muscle mass, fiber morphology, and cross-sectional area of muscles fibers of the hind limb muscles (quadriceps, gastrocnemius, plantaris, tibialis anterior and soleus), as well as the fiber type composition of the soleus muscle of wildtype (wt), heterozygous (oim/+), and homozygous (oim/oim) mice. Our results demonstrate that the muscle mass/body mass, fiber morphology, cross-sectional area of hindlimb muscles, as well as fiber type composition of the soleus muscle of oim, oim/+ relative to wt (+/+) mouse muscles were not significantly different between the genotypes. We correlated our morphologic findings with a functional contractile assay and determined that muscle tension-force generation and nerve conduction are not impaired in oim/oim or oim/+ mice. These findings suggest that oim and oim/+ mice do not have inherent muscle pathology. This knowledge is important in our ultimate understanding of skeletal muscle in OI model mice and ultimately, humans with this disease.Life Sciences Undergraduate Research Opportunity Progra

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)