Evolution over time of mackinawite generated on carbon steel by the SRB metabolic activity: an in-operando Raman study.

Mackinawite was biologically synthetized by immersing carbon steel coupons in artificial seawater containing Sulphate-Reducing Bacteria (SRB) for 6 months. These coupons were removed from the culture medium solution and some were stored in air while others were placed in SRB-free culture medium solution. In operando Raman spectroscopy was used to analyse all these coupons immediately after extraction from the incubation medium and nanocrystalline, well-crystallized and partially oxidized mackinawite was detected. The evolution of these corrosion products was also monitored as a function of ageing time with this technique. Nanocrystalline and well-crystallised mackinawite transformed into partially oxidised mackinawite, greigite and sulphate green rust for an ageing time between 4 and 72 h. After 120 h, maghemite, magnetite, lepidocrocite, goethite appeared on the coupons placed in SRB-free culture medium solution as opposed to those stored in air atmosphere. Greigite and sulphate green rust were not observed for Raman measurements performed in air.

Assessment of the severity of infant crying and its impact on parents: Development and validation of the ColiQ Questionnaire in France.

OBJECTIVES: The purpose of this study was to develop and validate a questionnaire that comprehensively assesses symptoms and severity of crying, symptoms suggesting infant functional gastrointestinal discomfort, and its impact on parents' quality of life: the Infant Colic Questionnaire (ColiQ©). For the first time, parents had access to a web application to follow their infants' evolving symptoms with a daily questionnaire. METHODS: The ColiQ was developed with a board of clinical experts (physicians and psychologists) based on extensive parent input. A longitudinal, observational study was conducted in France for 3 months. ColiQ assessments were collected online at six different time points. Psychometric testing demonstrated that ColiQ has acceptable psychometric properties (reliability, internal consistency, construct validity, and responsiveness). RESULTS: The ColiQ is a 16-question instrument developed in French including ten questions describing symptoms (Infant score) and six questions describing impacts (Parent score). The ColiQ demonstrated good test-retest reliability (ICC >0.70), internal consistency for both the Symptom and Impact subscale scores (Cronbach's α >0.70), and construct validity. Responsiveness was good; the ColiQ was able to detect significant improvement in the target population as early as 1 month (p<0.05). The global ColiQ score discriminated between severity levels (mild, medium, severe). CONCLUSIONS: The ColiQ was developed with input from parents and healthcare professionals and has shown validity, reliably, and responsiveness to change. Parents can use the web application to follow how their infants' symptoms evolve. The ColiQ can help parents quantify and verbalize their concerns during consultations, and provides an opportunity to facilitate conversations between the physician and parents.

CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies.

Patient-specific prescriber feedback can increase the rate of osteoporosis screening and treatment: results from two national interventions.

Osteoporosis interventions targeting older Australians and clinicians were conducted in 2008 and 2011 as part of a national quality improvement program underpinned by behavioural theory and stakeholder engagement. Uptake of bone mineral density (BMD) tests among targeted men and women increased after both interventions and sustained increases in osteoporosis treatment were observed among men targeted in 2008. PURPOSE: Educational interventions incorporating patient-specific prescriber feedback have improved osteoporosis screening and treatment among at-risk patients in clinical trials but have not been evaluated nationally. This study assessed uptake of BMD testing and osteoporosis medicines following two national Australian quality improvement initiatives targeting women (70-79 years) and men (75-85 years) at risk of osteoporosis. METHODS: Administrative health claims data were used to determine monthly rates of BMD testing and initiation of osteoporosis medicines in the 9-months post-intervention among targeted men and women compared to older cohorts of men and women. Log binomial regression models were used to assess differences between groups. RESULTS: In 2008 91,794 patients were targeted and 52,427 were targeted in 2011. There was a twofold increase in BMD testing after each intervention among targeted patients compared to controls (p < 0.001). Initiation of osteoporosis medicines increased by 21% among men targeted in 2008 and 34% among men targeted in 2011 compared to older controls (p < 0.01). Initiation of osteoporosis medicines among targeted women was similar to the older controls. CONCLUSION: Programs underpinned by behavioural theory and stakeholder engagement that target both primary care clinicians and patients can improve osteoporosis screening and management at the national level.

Multi-laboratory evaluation of SkinEthic HCE test method for testing serious eye damage/eye irritation using solid chemicals and overall performance of the test method with regard to solid and liquid chemicals testing.

A prospective multicentre study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITS protocol for solids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 35 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 95% (57/60) and 96.8% (92/95) for the extended data set. Furthermore, the overall concordance between the laboratories was 96.7% (58/60). The accuracy of the SkinEthic™ HCE EITS for the extended dataset, based on bootstrap resampling, was 81.0% (95% CI: 78.9% to 83.2%) with a sensitivity of 90.5% (95% CI: 88.1% to 92.9%) and specificity of 73.6% (95% CI: 71.7% to 75.5%). Overall, 200 chemicals were tested (105 liquids (EITL protocol) and 95 solids (EITS protocol)) resulting in a sensitivity of 95.2%, specificity of 72.1% and accuracy of 83.7%, thereby meeting all acceptance criteria for predictive capacity.

Multi-laboratory validation of SkinEthic HCE test method for testing serious eye damage/eye irritation using liquid chemicals.

A prospective multicentric study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITL protocol for liquids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 45 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 88.3% (53/60) and 92.4% (97/105) for the extended data set. Furthermore, the overall concordance between the laboratories was 93.3% (56/60). The accuracy of the SkinEthic™ HCE EITL for the extended dataset, based on bootstrap resampling, was 84.4% (95% CI: 81.9% to 87.6%) with a sensitivity of 99.0% (95% CI: 96.4% to 100%) and specificity of 68.5% (95% CI: 64.0% to 74.0%), thereby meeting all acceptance criteria for predictive capacity. This efficient transferable and reproducible assay is a promising tool to be integrated within a battery of assays to perform an eye irritation risk assessment.

Gender differences in dietary intakes: what is the contribution of motivational variables?

BACKGROUND: Differences between men and women with respect to dietary intakes and eating behaviours have been reported and could be explained by gender differences in motivational variables associated with the regulation of food intake. The main objectives of the present study were to identify gender differences in dietary intakes, eating behaviours and motivational variables and to determine how motivational variables were associated with dietary intakes and eating behaviours in men and women. METHODS: Sixty-four men and 59 premenopausal women were included in the present study and presented cardiovascular risk factors. The Regulation of Eating Behaviours scale was completed to assess motivational variables. A validated food frequency questionnaire was administered to evaluate dietary intakes and subjects completed the Three-Factor Eating questionnaire to assess eating behaviours. RESULTS: Men had higher energy intake, energy density and percentage of energy from lipids and lower percentage of energy from carbohydrates than women (P ≤ 0.04). Men also had a lower emotional susceptibility to disinhibition than women (P = 0.0001). Women reported a higher score for eating-related self-determined motivation [i.e., eating-related self-determination index (SDI)] than men (P = 0.002). The most notable gender difference in the pattern of associations was that eating-related SDI was negatively associated with energy density (r = -0.30; P = 0.02), only in women. CONCLUSIONS: Women had a better dietary profile and higher eating-related SDI than men. However, gender differences in dietary variables might be explained by a potential gender-specific pattern of association of eating-related SDI with dietary intakes and eating behaviours.

Prostate apoptosis response-4 mediates TGF-ß-induced epithelial-to-mesenchymal transition.

A growing body of evidence supports that the epithelial-to-mesenchymal transition (EMT), which occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Transforming growth factor-ß (TGF-ß) is known to induce EMT in a number of cancer cell types; however, the mechanism underlying this transition process is not fully understood. In this study we have demonstrated that TGF-ß upregulates the expression of tumor suppressor protein Par-4 (prostate apoptosis response-4) concomitant with the induction of EMT. Mechanistic investigations revealed that exogenous treatment with each TGF-ß isoform upregulates Par-4 mRNA and protein levels in parallel levels of phosphorylated Smad2 and IκB-α increase. Disruption of TGF-ß signaling by using ALK5 inhibitor, neutralizing TGF-ß antibody or phosphoinositide 3-kinase inhibitor reduces endogenous Par-4 levels, suggesting that both Smad and NF-κB pathways are involved in TGF-ß-mediated Par-4 upregulation. NF-κB-binding sites in Par-4 promoter have previously been reported; however, using chromatin immunoprecipitation assay we showed that Par-4 promoter region also contains Smad4-binding site. Furthermore, TGF-ß promotes nuclear localization of Par-4. Prolonged TGF-ß3 treatment disrupts epithelial cell morphology, promotes cell motility and induces upregulation of Snail, vimentin, zinc-finger E-box binding homeobox 1 and N-Cadherin and downregulation of Claudin-1 and E-Cadherin. Forced expression of Par-4, results in the upregulation of vimentin and Snail expression together with increase in cell migration. In contrast, small interfering RNA-mediated silencing of Par-4 expression results in decrease of vimentin and Snail expression and prevents TGF-ß-induced EMT. We have also uncovered a role of X-linked inhibitor of apoptosis protein in the regulation of endogenous Par-4 levels through inhibition of caspase-mediated cleavage. In conclusion, our findings suggest that Par-4 is a novel and essential downstream target of TGF-ß signaling and acts as an important factor during TGF-ß-induced EMT.

ERα-targeted therapy in ovarian cancer cells by a novel estradiol-platinum(II) hybrid.

As we previously showed, we have synthesized a new family of 17ß-estradiol-platinum(II) hybrids. Earlier studies revealed the VP-128 hybrid to show high efficiency compared with cisplatin toward hormone-dependent breast cancer cells. In the present research, we have studied the antitumor activity of VP-128 in vitro and in vivo against ovarian cancer. In nude mice with ovarian xenografts, VP-128 displayed selective activity toward hormone-dependent tumors and showed higher efficiency than cisplatin to inhibit tumor growth. Similarly, in vitro, transient transfection of estrogen receptor (ER)-α in ERα-negative A2780 cells increased their sensitivity to VP-128-induced apoptosis, confirming the selectivity of VP-128 toward hormone-dependent tumor cells. In agreement, Western blot analysis revealed that VP-128 induced higher caspase-9, caspase-3, and poly (ADP-ribose) polymerase cleavage compared with cisplatin. The activation of caspase-independent apoptosis was also observed in ERα-negative A2780 cells, in which VP-128 rapidly induced the translocation of apoptosis-inducing factor to the nucleus. Conversely, subcellular localization of apoptosis-inducing factor was not modified in ERα-positive Ovcar-3 cells. We also discovered that VP-128 induces autophagy in ovarian cancer cells because of the formation of acidic vesicular organelles (AVOs) and increase of Light Chain 3B-II protein responsible for the formation of autophagosomes; pathways related to autophagy (AKT and mammalian target of rapamycin) were also down-regulated, supporting this mechanism. Finally, the inhibition of autophagy using chloroquine increased VP-128 efficiency, indicating a possible combination therapy. Altogether these results highlight the beneficial value of VP-128 for the treatment of hormone-dependent ovarian cancers and provide preliminary proof of concept for the efficient targeting of ERα- by 17ß-estradiol-Pt(II)-linked chemotherapeutic hybrids in these tumors.

Effect of stress on clinical reasoning during simulated ambulatory consultations.

BACKGROUND: The goal of this study was to examine the impact of subjective and physiological stress responses on medical students' diagnostic reasoning and communication skills. METHOD: A prospective randomized quantitative study was undertaken, looking at ambulatory consultations in internal medicine. On the first day (baseline day), volunteer year 6 students (n = 41) participated in a simulated ambulatory consultation with standardized patients (SPs). On the second day (study day), one week later, they were randomly assigned to two groups: a low stress (n = 20) and a high stress (n = 21) simulated ambulatory consultation. Stress was measured using validated questionnaires and salivary cortisol. The SPs assessed the students' reasoning and communication. The students completed assessments of their clinical reasoning after the consultations. RESULTS: Although stress measures were all significantly higher in the high-stress condition (all p < 0.05), no differences were found in diagnostic accuracy and justification scores. However, correlational analyses revealed a negative correlation between multiple-stress measures and the students' ability to generate arguments for differential diagnoses. CONCLUSION: Stress was associated with impairments in clinical reasoning, of a nature typically suggestive of premature closure.

Prescribing for older people with chronic renal impairment.

BACKGROUND: Renal function is an important prescribing consideration. On average, glomerular filtration rate declines by about 10 mL/min every 10 years after the age of 40. Renal impairment may cause medicines to accumulate or cause toxicity, especially if the medicine has a narrow therapeutic index. OBJECTIVE: To present an overview of prescribing considerations in the primary care setting for patients with chronic renal impairment. DISCUSSION: Serum creatinine considered in isolation is not a reliable indicator of renal function. The estimated glomerular filtration rate provided in pathology reporting can alert prescribers to possible renal impairment and the need to consider dose adjustments. The Cockcroft-Gault equation should be used to adjust medicine doses. Renal function monitoring is recommended for patients using medicines that can impair renal function or cause nephrotoxicity (eg. NSAIDs, ACEIs, ARBs).

Improved procedural performance following a simulation training session may not be transferable to the clinical environment.

OBJECTIVE: Neonatal intubation is a life-saving procedural skill required by pediatricians. Trainees receive insufficient clinical exposure to develop this competency. Traditional training comprises a Neonatal Resuscitation Program (NRP) complemented by clinical experience. More recently, simulation is being used in procedural skills training. The objective of this study is to examine the impact of a simulation session, which teaches the skill of neonatal intubation by comparing pre- and post-intervention performance, and examining transferability of skill acquisition to the clinical setting. STUDY DESIGN: First-year pediatric residents with NRP training, but no previous neonatal experience, attended a 2-h intubation education session conducted by two experienced respiratory therapists. Individual components of the skill were taught, followed by practice on a high-fidelity infant mannequin with concurrent feedback. Skills were assessed using a validated neonatal intubation checklist (CL) and a five-point global rating scale (GRS), pre- and immediately post-intervention, using the mannequin. Clinical intubations performed in the subsequent 8-week neonatal intensive-care unit (NICU) rotation were evaluated by documenting success rates, time taken to intubate, and CL and GRS scores. Performance was also compared with similar data collected on intubations performed by a historical cohort of first-year residents who did not receive the training intervention. Data were analyzed using descriptive statistics, Student's t-test and χ (2)-test as appropriate, and analysis of variance. RESULT: Thirteen residents participated in the educational session. Mean pre-intervention CL score was 65.4 ± 18% (s.d.) and GRS was 3 ± 0.7 (s.d.). Performance improved following the intervention with post-training CL score of 93 ± 5% (P<0.0001) and GRS of 3.92 ± 0.4 (P=0.0003). These trainees performed 40 intubations during their subsequent NICU rotation, with a success rate of 67.5% compared with 63.15% in the cohort group (NS). However, mean CL score for the study trainees during the NICU rotation was 64.6 ± 20%, significantly lower than their post-training CL score (P<0.001), and significantly lower than the historical cohort score of 82.5 ± 15.4% (P=0.001). In the intervention group, there were no significant differences between the pre-intervention and real-life CL scores of 65 ± 18% and 64.63 %, respectively, and the pre-intervention and real-life GRS of 3.0 ± 0.7 and 2.95 ± 0.86, respectively. CONCLUSION: Trainees showed significant improvement in intubation skills immediately post intervention, but this did not translate into improved-clinical performance, with performance returning to baseline. In fact, significantly higher CL scores were demonstrated by the cohort group. These data suggest that improved performance in the simulation environment may not be transferable to the clinical setting. They also support the evidence that although concurrent feedback may lead to improved performance immediately post training intervention, this does not result in improved skill retention overall.

High-fidelity simulator technology may not be superior to traditional low-fidelity equipment for neonatal resuscitation training.

OBJECTIVE: Despite completing accredited resuscitation training, neonatal trainees often feel unprepared to deal with real-life clinical emergencies. High-fidelity simulator (HFS) technology offers the potential of recreating a realistic stressful clinical environment to aid training and evaluation. To date, there are limited data examining the physiological impact of this training modality in comparison to less costly alternatives. The objective of this study was to compare the effects of low-fidelity simulator (LFS) versus HFS technology on performance levels, objective and subjective measures of stress in neonatal trainees. STUDY DESIGN: Sixteen neonatal fellows were invited to participate in a prospective randomized study. Subjects were divided into pairs and randomized to LFS or HFS for completion of scenario I. After an interval of 1 month, fellow teams crossed over to complete scenario II using the alternative simulator technology. Technical and non-technical skills were assessed using validated resuscitation scoring tools. Participants recorded subjective stress at sequential time points before and after each simulation. Buccal cortisol was measured at each corresponding time point and comparison between HFS and LFS groups was made. RESULT: The mean overall resuscitation performance score was 75.8%±10, but there was no difference in performance between HFS and LFS groups. There was also no significant difference in non-technical skills performance between groups. Salivary cortisol increased over the duration of the simulated experience, but there were no differences between the two groups (P=0.001, two-way repeated measures analysis of variance). We also identified changes in subjective measures of stress (P<0.001, analysis of variance) over time, but again there were no differences between groups. CONCLUSION: Simulated neonatal resuscitations induce a significant stress response in neonatal trainees; however, we were unable to identify any difference in stress measures between HFS and LFS. These data suggest that HFS technology offers no additional stress-inducing benefit.

Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE).

OBJECTIVES: Patients with advanced ankylosing spondylitis (AS) experience disability because of reduced spinal mobility and pulmonary function impairment. This placebo-controlled study evaluated the effect of etanercept (ETN) in patients with advanced AS. METHODS: A multicentre randomised double-blind placebo-controlled trial of 12 weeks' duration was performed. Patients had definite (modified New York criteria), active (Bath AS Disease Activity Index (BASDAI) ≥40), severe (radiological intervertebral bridges) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive. They were treated with ETN 50 mg once weekly or identical placebo (PBO). RESULTS: Of the 95 patients screened, 82 were randomised to receive ETN (n=39) or PBO (n=43). At baseline the disease was active (mean BASDAI 61.0±13.4, C reactive protein (CRP) 20.7±25.5 mg/l) and severe (mean Bath AS Metrology Index (BASMI) 5.7±1.3, mSASSS 36.5±20.5); forced pulmonary vital capacity (FVC) was 3.3±0.7 l. Improvement in BASDAI (normalised net incremental area under the curve between baseline and week 12, primary end point) was significantly greater in the ETN group than in the PBO group (-19.8±16.5 vs -11.0±16.4, p=0.019). Moreover, at week 12, ETN gave better results than PBO for the BASDAI (-26.4±19.7 vs -14.4±19.7; p=0.008), total back pain (-29.2±24.0 vs -14.9±24.0; p=0.010), BASFI (-21.7±17.6 vs -10.1±17.6; p=0.004), BASMI (-0.6±0.6 vs -0.2±0.6; p=0.011), CRP level (-15.7±14.2 vs -1.3±14.2; p<0.001) and FVC (+160±280 ml vs -20±280 ml; p=0.006). CONCLUSIONS: ETN has short-term efficacy for patients with advanced AS, as was previously reported for less advanced disease. The efficacy is observed for the main symptoms (pain) and on markers of inflammation (CRP), as well as disease severity in terms of spinal mobility and pulmonary function.

Oscillatory response in a sensory network of ON and OFF cells with instantaneous and delayed recurrent connections.

A neural field model with multiple cell-to-cell feedback connections is investigated. Our model incorporates populations of ON and OFF cells, receiving sensory inputs with direct and inverted polarity, respectively. Oscillatory responses to spatially localized stimuli are found to occur via Andronov-Hopf bifurcations of stationary activity. We explore the impact of multiple delayed feedback components as well as additional excitatory and/or inhibitory non-delayed recurrent signals on the instability threshold. Paradoxically, instantaneous excitatory recurrent terms are found to enhance network responsiveness by reducing the oscillatory response threshold, allowing smaller inputs to trigger oscillatory activity. Instantaneous inhibitory components do the opposite. The frequency of these response oscillations is further shaped by the polarity of the non-delayed terms.

Failure of pediatric and neonatal trainees to meet Canadian Neonatal Resuscitation Program standards for neonatal intubation.

OBJECTIVE: Neonatal intubation skills are initially taught through the Neonatal Resuscitation Program (NRP) and thereafter complemented by further practical clinical training. The aim of this study is to compare the ability of NRP trained individuals to successfully complete a neonatal intubation. STUDY DESIGN: A prospective observational study was performed at an inborn high-risk level 3 perinatal center. Participants were postgraduate years 1 and 3 pediatric residents, neonatal-perinatal medicine subspecialty residents and fellows, and neonatal intensive care unit (NICU) respiratory therapists (RTs) with earlier NRP training. Intubations were scored on a checklist as well as a global assessment scale. Characteristics of the intubation attempt were recorded for each patient. RESULT: Fifty neonatal intubations were assessed, of which 73% of the attempts were deemed successful. A higher proportion of endotracheal tubes were successfully placed by RTs (100%, P<0.05), compared with both NICU fellows (69%) and pediatric residents (63%). The overall mean time for successful neonatal intubation was 51+/-28 s, which is greater than twice the time currently recommended by the NRP and American Heart Association guidelines. Attempts by pediatric residents and NICU fellows were longer (P<0.05, analysis of variance) and received lower global assessment scale (P<0.05, analysis of variance) and checklist (P<0.05, analysis of variance) scores, when compared with RTs. CONCLUSION: The success rate and overall quality of neonatal intubations performed by neonatal and pediatric trainees in Canada did not meet NRP standards; in particular, the time taken to intubate by pediatric residents and neonatal fellows is concerning. Re-evaluation of training methods and the volume of formalized exposure to neonatal intubation in Canadian residency programs are required.

Efficacy of high-fidelity simulation debriefing on the performance of practicing anaesthetists in simulated scenarios.

BACKGROUND: Research into adverse events in hospitalized patients suggests that a significant number are preventable. The purpose of this randomized, controlled study was to determine if simulation-based debriefing improved performance of practicing anaesthetists managing high-fidelity simulation scenarios. METHODS: The anaesthetists were randomly allocated to Group A: simulation debriefing; Group B: home study; and Group C: no intervention and secondary randomization to one of two scenarios. Six to nine months later, subjects returned to manage the alternate scenario. Facilitators blinded to study group allocation completed the performance checklists (dichotomously scored checklist, DSC) and Global Rating Scale of Performance (GRS). Two non-expert raters were trained, and assessed all videotaped performances. RESULTS: Interim analysis indicated no difference between Groups B and C which were merged into one group. Seventy-four subjects were recruited, with 58 complete data sets available. There was no significant effect of group on pre-test scores. A significant improvement was seen between pre- and post-tests on the DSC in debriefed subjects (pre-test 66.8%, post-test 70.3%; F(1,57)=4.18, P=0.046). Both groups showed significant improvement in the GRS over time (F(1,57)=5.94, P=0.018), but no significant difference between the groups. CONCLUSIONS: We found a modest improvement in performance on a DSC in the debriefed group and overall improvement in both control and debriefed groups using a GRS. Whether this improvement translates into clinical practice has yet to be determined.

Cognitive behaviour therapy and medication in the treatment of obsessive-compulsive disorder.

OBJECTIVE: To compare cognitive behaviour therapy (CBT) with CBT plus medication; medication alone; and placebo in the treatment of adult obsessive-compulsive disorder (OCD). METHOD: Forty-eight participants (43 completers) were recruited into two protocols. In the first protocol, 21 people with OCD were randomly allocated to either a standard medication (fluvoxamine) or standard placebo condition for a 5-month period. Both these groups subsequently received CBT for a further 5 months. In the second protocol, 22 people with OCD received CBT, one group was already stabilized on an antidepressant of choice; the second group was drug naïve. RESULTS: All active treatments, but not the placebo, showed clinical improvement. There was no difference in treatment response to CBT regardless of whether participants had previously received medication or placebo. CONCLUSION: CBT has a more specific antiobsessional effect than medication but CBT plus medication shows greatest overall clinical improvement in mood.

Achieving a sustained reduction in benzodiazepine use through implementation of an area-wide multi-strategic approach.

OBJECTIVE: This study aimed to evaluate the impact, in a regional setting, of a multi-strategic partnership approach for reducing benzodiazepine use in the management of insomnia, as recommended in Australia's National Policy on Quality Use of Medicines. METHOD: The setting was a rural region of South Australia, covering approximately 2000 km2, with a population of over 20 000. The study involved participatory action research, with qualitative and quantitative evaluations. The intervention involved a multi-strategic approach, including provision of treatment guidelines, provision of consumer information, a local media campaign and education and training of health professionals. The quantitative evaluation involved a single region before/after study with 2 years of follow-up using pharmacy-based dispensing data for benzodiazepines and antidepressants, gathered for the months of November to April in 1998/99 ('before' period) through to 2000/01 ('after' period). The data were analysed using non-parametric statistics. RESULTS: There was a 19% reduction in benzodiazepine dispensing 2 years after the intervention compared with a 6% reduction nationally. Dispensing of antidepressants increased by 33%, compared with a 28% increase nationally. CONCLUSION: It was concluded that the multi-strategic approach to the management of sleep disorders proved successful in promoting the use of non-drug alternatives, achieving sustained reduction in benzodiazepine consumption in a rural community, without therapeutic substitution of antidepressants. IMPLICATIONS: The study demonstrated that a sustainable reduction in prescribing of benzodiazepines can be achieved through the implementation of a multi-strategic approach involving local consumers, health professionals, a Division of General Practice, a government department, aged-care facilities and the local media.