Facing up to binge drinking: Reducing binge drinking in adolescent males

Objective: To evaluate the effectiveness of an oro-facial trauma-based brief intervention, designed to raise adolescent males’ awareness about the immediate dangers of binge drinking.
Design: Non-randomised controlled exploratory trial
Setting: Secondary level schools
Materials & Methods: Pre, post and follow up validated questionnaires were used to assess a variety of descriptive data and changes in behaviour. Sixty Year 12 students were recruited in the pilot study and 182 in the definitive study.
Intervention: A brief visual presentation containing salient information and anonymised photographs relating to oro-facial injuries.
Main Outcome Measures: Intention to binge drink.
Results: The majority of participants obtained alcohol from off-license or licensed premises. At the commencement of the study, 68% of the participants were regular drinkers. Whilst there was no change in drinking behaviour, the intervention group reported that it was significantly more likely (compared to the control group) that they would reduce their drinking to less than binge levels.
Conclusion: The intervention resulted in participants reporting a more negative attitude towards binge drinking and increased their intention to disengage from binge drinking.

Understanding online customer repurchasing intention and the mediating role of trust - an empirical investigation in two developed countries

Although e-commerce adoption and customers initial purchasing behavior have been well studied in the literature, repeat purchase intention and its antecedents remain understudied. This study proposes a model to understand the extent to which trust mediates the effects of vendor-specific factors on customers intention to repurchase from an online vendor. The model was tested and validated in two different country settings. We found that trust fully mediates the relationships between perceived reputation, perceived capability of order fulfillment, and repurchasing intention, and partially mediates the relationship between perceived website quality and repurchasing intention in both countries. Moreover, multi-group analysis reveals no significant between-country differences of the model with regards to the antecedents and outcomes of trust, except the effect of reputation on trust. Academic and practical implications and future research are discussed. © 2009 Operational Research Society Ltd.

Attitudes, norms, identity and environmental behaviour: Using an expanded theory of planned behaviour to predict participation in a kerbside recycling programme

In an effort to contribute to greater understanding of norms and identity in the theory of planned behaviour, an extended model was used to predict residential kerbside recycling, with self-identity, personal norms, neighbourhood identification, and injunctive and descriptive social norms as additional predictors. Data from a field study (N = 527) using questionnaire measures of predictor variables and an observational measure of recycling behaviour supported the theory. Intentions predicted behaviour, while attitudes, perceived control, and the personal norm predicted intention to recycle. The interaction between neighbourhood identification and injunctive social norms in turn predicted personal norms. Self-identity and the descriptive social norm significantly added to the original theory in predicting intentions as well as behaviour directly. A replication survey on the self-reported recycling behaviours of a random residential sample (N = 264) supported the model obtained previously. These findings offer a useful extension of the theory of planned behaviour and some practicable suggestions for pro-recycling interventions. It may be productive to appeal to self-identity by making people feel like recyclers, and to stimulate both injunctive and descriptive norms in the neighbourhood.

The addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for advanced colorectal cancer: results of the MRC COIN trial.

Background: In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival.
Methods: In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448.
Findings: 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3—29·2] in the control group vs 17·0 months [9·4—30·1] in the cetuximab group; HR 1·04, 95% CI 0·87—1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0—12·5] in the control group vs 8·6 months [5·1—13·8] in the cetuximab group; HR 0·96, 0·82—1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5—27·4); KRAS mutant, 14·4 months (8·5—24·0); all wild-type, 20·1 months (11·5—31·7).
Interpretation: This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended.

Removing the threat of diclofenac to critically endangered Asian vultures

Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in South Asia has resulted in the collapse of populations of three vulture species of the genus Gyps to the most severe category of global extinction risk. Vultures are exposed to diclofenac when scavenging on livestock treated with the drug shortly before death. Diclofenac causes kidney damage, increased serum uric acid concentrations, visceral gout, and death. Concern about this issue led the Indian Government to announce its intention to ban the veterinary use of diclofenac by September 2005. Implementation of a ban is still in progress late in 2005, and to facilitate this we sought potential alternative NSAIDs by obtaining information from captive bird collections worldwide. We found that the NSAID meloxicam had been administered to 35 captive Gyps vultures with no apparent ill effects. We then undertook a phased programme of safety testing of meloxicam on the African white-backed vulture Gyps africanus, which we had previously established to be as susceptible to diclofenac poisoning as the endangered Asian Gyps vultures. We estimated the likely maximum level of exposure (MLE) of wild vultures and dosed birds by gavage (oral administration) with increasing quantities of the drug until the likely MLE was exceeded in a sample of 40 G. africanus. Subsequently, six G. africanus were fed tissues from cattle which had been treated with a higher than standard veterinary course of meloxicam prior to death. In the final phase, ten Asian vultures of two of the endangered species (Gyps bengalensis, Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the likely MLE dosage. All meloxicam-treated birds survived all treatments, and none suffered any obvious clinical effects. Serum uric acid concentrations remained within the normal limits throughout, and were significantly lower than those from birds treated with diclofenac in other studies. We conclude that meloxicam is of low toxicity to Gyps vultures and that its use in place of diclofenac would reduce vulture mortality substantially in the Indian subcontinent. Meloxicam is already available for veterinary use in India.

Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

Background: Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. Methods: In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. Findings: Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). Interpretation: Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought.

Evaluation of information extraction techniques to label extracted data from e-commerce web page

Automatically determining and assigning shared and meaningful text labels to data extracted from an e-Commerce web page is a challenging problem. An e-Commerce web page can display a list of data records, each of which can contain a combination of data items (e.g. product name and price) and explicit labels, which describe some of these data items. Recent advances in extraction techniques have made it much easier to precisely extract individual data items and labels from a web page, however, there are two open problems: 1. assigning an explicit label to a data item, and 2. determining labels for the remaining data items. Furthermore, improvements in the availability and coverage of vocabularies, especially in the context of e-Commerce web sites, means that we now have access to a bank of relevant, meaningful and shared labels which can be assigned to extracted data items. However, there is a need for a technique which will take as input a set of extracted data items and assign automatically to them the most relevant and meaningful labels from a shared vocabulary. We observe that the Information Extraction (IE) community has developed a great number of techniques which solve problems similar to our own. In this work-in-progress paper we propose our intention to theoretically and experimentally evaluate different IE techniques to ascertain which is most suitable to solve this problem.

Sustained effectiveness of a multifaceted intervention to reduce potentially inappropriate prescribing in older patients in primary care (OPTI-SCRIPT study)

Background: Potentially inappropriate prescribing (PIP) is common in older people in primary care and can result in increased morbidity, adverse drug events and hospitalisations. We previously demonstrated the success of a multifaceted intervention in decreasing PIP in primary care in a cluster randomised controlled trial (RCT).
Objective: We sought to determine whether the improvement in PIP in the short term was sustained at 1-year follow-up.
Methods: A cluster RCT was conducted with 21 GP practices and 196 patients (aged ≥70) with PIP in Irish primary care. Intervention participants received a complex multifaceted intervention incorporating academic detailing, medicine review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions at 1-year follow-up. Intention-to-treat analysis using random effects regression was used.
Results: All 21 GP practices and 186 (95 %) patients were followed up. We found that at 1-year follow-up, the significant reduction in the odds of PIP exposure achieved during the intervention was sustained after its discontinuation (adjusted OR 0.28, 95 % CI 0.11 to 0.76, P = 0.01). Intervention participants had significantly lower odds of having a potentially inappropriate proton pump inhibitor compared to controls (adjusted OR 0.40, 95 % CI 0.17 to 0.94, P = 0.04).
Conclusion: The significant reduction in the odds of PIP achieved during the intervention was sustained after its discontinuation. These results indicate that improvements in prescribing quality can be maintained over time.

Interventions to Promote Follow-up After Trabeculectomy Surgery in Rural Southern China: A Randomized Clinical Trial.

Importance:

Follow-up after trabeculectomy surgery is important to surgical success, but little is known about the effect of interventions on improving follow-up in low-resource areas.

Objective:

To examine whether text message reminders and free eye medications improve follow-up after trabeculectomy in rural southern China.

Design, Setting, and Participants:

This randomized clinical trial studied 222 consecutive patients undergoing trabeculectomy from October 1, 2014, through November 31, 2015, at 4 rural hospitals in Guangdong and Guangxi Provinces, China. Data from the intention-to-treat population were analyzed.

Interventions:

Patients undergoing trabeculectomy were randomized (1:1) to receive text message reminders 3 days before appointments at 1 and 2 weeks and 1 month after surgery and free topical corticosteroid medication (US$5.30) at each visit or to standard follow-up without reminders or free medication.

Main Outcomes and Measure:

Follow-up at 1 month postoperatively.

Results:

Among 222 eligible patients, 13 (5.9%) refused and 209 (94.1%) were enrolled, with 106 (50.7%) randomized to the intervention group (mean [SD] age, 64.4 [12.7] years; 56 women [52.8%]) and 103 (49.3%) to the control group (mean [SD] age, 63.0 [12.7] years; 53 women [51.5%]). A total of 6 patients (2.9%) were unavailable for follow-up. Attendance at 1 month for the intervention group (59 of 102 [57.8%]) was significantly higher than for the control group (34 of 101 [33.7%]) (unadjusted relative risk [RR], 1.72; 95% CI, 1.13-2.63; P = .01). Factors associated with 1-month attendance in multiple regression models included intervention group membership (RR, 1.65; 95% CI, 1.08-2.53; P = .02) and being told to return for suture removal (RR, 1.80; 95% CI, 1.06-3.06; P = .03). One-month attendance among controls not told about suture removal was 3 of 31 (9.7%), whereas it was 44 of 68 (64.7%) among the intervention group with suture removal (unadjusted RR, 6.69; 95% CI, 2.08-21.6; P = .001).

Conclusions and Relevance:

In this setting, low-cost interventions may significantly improve postoperative follow-up after glaucoma surgery, a potential opportunity for interventions known to improve surgical success.

A Multicenter, Randomised Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide

AIM: To compare early (15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease. METHODS: Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age 30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily. RESULTS: There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance. CONCLUSIONS: Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective

PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma

Summary Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1–4, 8–11 and 15–18 during cycle 1 and days 1–4 during cycles 2–4. During days 1–4, patients also received 0, 4·5 or 9 mg/m2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.

The effect of volition on the stability of bimanual coordination

The authors investigated how the intention to passively perform a behavior and the intention to persist with a behavior impact upon the spatial and temporal properties of bimanual coordination. Participants (N = 30) were asked to perform a bimanual coordination task that demanded the continuous rhythmic extension-flexion of the wrists. The frequency of movement was scaled by an auditory metronome beat from 1.5 Hz, increasing to 3.25 Hz in .25-Hz increments. The task was further defined by the requirement that the movements be performed initially in a prescribed pattern of coordination (in-phase or antiphase) while the participants assumed one of two different intentional states: stay with the prescribed pattern should it become unstable or do not intervene should the pattern begin to change. Transitions away from the initially prescribed pattern were observed only in trials conducted in the antiphase mode of coordination. The time at which the antiphase pattern of coordination became unstable was not found to be influenced by the intentional state. In addition, the do-not-intervene set led to a switch to an in-phase pattern of coordination whereas the stay set led to phase wandering. Those findings are discussed within the framework of a dynamic account of bimanual coordination.

Durability of Self-Compacting Concrete

Because of the different mix design in comparison with traditional concrete and the absence of vibration, different durability characteristics might be expected for self-compacting concrete. The stateof- the-art report, prepared by RILEM Technical Committee TC 205-DSC focuses on the Durability of SCC, by first gathering the available information concerning pore structure, air-void system and transport mechanisms. The available durability results are studied and summarised keeping in mind the fundamental mechanisms and driving forces. All relevant durability issues are considered, like carbonation, chloride penetration, frost resistance, ASR, sulphate attack, thaumasite formation, fire resistance, etc... It is not the intention to give a review on these durability aspects for concrete in general. The aim however is to point at the specifics related to the use of SCC, e.g. due to the addition of a large amount of limestone filler, etc... This paper summarizes the main conclusions of the State-of-the-Art Report.

Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

Background
Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the eff ect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods
We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks’ and 22 weeks’ gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive1000 mg vitamin C and 400 IU vitamin E (a-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratifi ed by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defi ned as gestational hypertension with proteinuria. Analysis was by modifi ed intention to treat. This study is registered, ISRCTN27214045.

Findings
Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70)groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.

Interpretation
Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be benefi cial in women with a low antioxidant status at baseline needs further testing.