The effectiveness of a standardised preoperative preparation in reducing child and parent anxiety: a single-blind randomised controlled trial.

AIMS: To evaluate the effect of a structured preoperative preparation on child and parent state anxiety, child behavioural change and parent satisfaction. BACKGROUND: It is estimated that around 50-70% of hospitalised children experience severe anxiety and distress prior to surgery. Children who are highly anxious and distressed preoperatively are likely to be distressed on awakening and have negative postoperative behaviour. Although education before surgery has been found to be useful mostly in North America, the effectiveness of preoperative preparation programme adapted to the Australian context remains to be tested. DESIGN: This single-blind randomised controlled study was conducted at a tertiary referral hospital for children in Western Australia. METHODS: Following ethics approval and parental consent, 73 children and one of their carers (usually a parent) were randomly assigned into two groups. The control group had standard practice with no specific preoperative education and the experimental group received a preoperative preparation, including a photo file, demonstration of equipment using a role-modelling approach and a tour. RESULTS: The preoperative preparation reduced parent state anxiety significantly (-2·32, CI -4·06 to -0·56, p = 0·009), but not child anxiety (-0·59, CI -1·23 to 0·06, p = 0·07). There was no significant difference in child postoperative behaviour or parent satisfaction between the groups. There was a significant two-point pain score reduction in the preoperative preparation group, when compared with the control group median 2 (IQR 5) and 4 (IQR 4), respectively (p = 0·001).¦CONCLUSIONS: Preoperative preparation was more efficient on parent than child. Although the preoperative preparation had limited effect on child anxiety, it permitted to decrease pain experience in the postoperative period.¦RELEVANCE TO CLINICAL PRACTICE: Parents should be actively involved in their child preoperative preparation.

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics.

OBJECTIVE: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. METHOD: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. RESULTS AND CONCLUSION: The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

Use of nicotine substitute prescribed at hourly plus ad libitum intake or ad libitum for heavy smokers willing to quit : a randomized controlled trial

Rapport de synthèse : l .Objectif Evaluer l'effet qu'ont les consignes d'utilisation régulière d'un spray nasal à la nicotine sur leur véritable utilisation durant les 3 premières semaines d'un sevrage tabagique. Un objectif secondaire est d'évaluer l'effet des consignes d'utilisation régulière du spray durant les premières semaines de sevrage tabagique sur le taux de succès à 6 mois par rapport à un groupe pouvant utiliser le spray « ad libitum ». 2. Méthode II s'agit d'une étude ouverte, randomisée contrôlée, incluant 50 patients présentant une dépendance nicotinique forte, se trouvant en phase de préparation selon le modèle transthéorique du changement de Prochaska et Di Clemente, recrutés au sein de la consultation «stop tabac » de la Policlinique Médicale Universitaire de Lausanne. Dans le groupe «contrôle », les patients ont été instruits à utiliser le spray « ad libitum », soit dès qu'apparaissaient des envies irrésistibles de fumer, tandis que le groupe «intervention » a reçu pour consigne d'utiliser le spray au moins 1 fois par heure dès le lever, voire plus en cas d'envie de fumer. L'utilisation du spray nasal a été enregistrée par un dispositif électronique fixé sur le spray (MDILogTM) durant les 3 premières semaines d'utilisation. Durant le suivi, l'abstinence tabagique a été vérifiée par une mesure du taux de CO expiré par un appareil spécifique (Bedfont Smokerlyzer). L'abstinence tabagique a été considérée comme un succès si le taux de CO était s 10 ppm (particules par million). 3. Résultats Un patient a été perdu durant le suivi. Au moment de la randomisation, le groupe «intervention » comprenait plus de femmes, des patients ayant un nombre plus grand de précédentes tentatives d'arrêt du tabagisme, plus de co-morbidités psychiatriques, mais moins de co-morbidités somatiques que le groupe «contrôle ». Dans les 2 groupes, les participants ont utilisé le spray nasal plus de 8 fois par jour (minimum demandé dans le groupe intervention). L'utilisation moyenne du spray était de 13,6 doses/jour pour le groupe «intervention » et de 1 l,l doses/jour pour le groupe contrôle. Ajusté aux différences entre les 2 groupes, la différence entre les doses plus importantes utilisées dans le groupe «intervention »par rapport à celles du groupe « ad libitum »reste non significative durant la première (0.8 ; CI 95% -5.1 ; 6,7), la deuxième (4.0 ; CI 95% -1.9 ; 9.9) et la troisième semaine (3.0 ; CI 95% -2.5 ; 8.5). De même, le fait d'instruire le patient à utiliser chaque heure le spray nasal durant les premières semaines n'a pas eu d'impact sur le taux de succès à 6 mois (RR = 0.69 ; CI 95% 0.34 ; 1.39). 4. Conclusions Cette étude négative montre que les différences d'utilisation du spray nasal nicotinique sont plus dépendantes des caractéristiques individuelles du patient que des recommandations d'utilisation du thérapeute. Les patients présentant un syndrome de dépendance à la nicotine forte utilisent spontanément de manière importante le spray nasal nicotinique, indépendamment des recommandations données. Pour les patients présentant un syndrome de dépendance à la nicotine forte, les recommandations par le thérapeute d'utiliser le spray nasal dès l'apparition d'envies de fumer semblent être la manière de faire la plus adéquate.

Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.

Community pharmacist intervention in depressed primary care patients (PRODEFAR study): randomized controlled trial protocol.

Background: Treatment of depression, the most prevalent and costly mental disorder, needs to be improved. Non-concordance with clinical guidelines and non-adherence can limit the efficacy of pharmacological treatment of depression. Through pharmaceutical care, pharmacists can improve patients' compliance and wellbeing. The aim of this study is to evaluate the effectiveness and costeffectiveness of a community pharmacist intervention developed to improve adherence and outcomes of primary care patients with depression. Methods/design: A randomized controlled trial, with 6-month follow-up, comparing patients receiving a pharmaceutical care support programme in primary care with patients receiving usual care. The total sample comprises 194 patients (aged between 18 and 75) diagnosed with depressive disorder in a primary care health centre in the province of Barcelona (Spain). Subjects will be asked for written informed consent in order to participate in the study. Diagnosis will be confirmed using the SCID-I. The intervention consists of an educational programme focused on improving knowledge about medication, making patients aware of the importance of compliance, reducing stigma, reassuring patients about side-effects and stressing the importance of carrying out general practitioners' advice. Measurements will take place at baseline, and after 3 and 6 months. Main outcome measure is compliance with antidepressants. Secondary outcomes include; clinical severity of depression (PHQ-9), anxiety (STAI-S), health-related quality of life (EuroQol-5D), satisfaction with the treatment received, side-effects, chronic physical conditions and sociodemographics. The use of healthcare and social care services will be assessed with an adapted version of the Client Service Receipt Inventory (CSRI). Discussion: This trial will provide valuable information for health professionals and policy makers on the effectiveness and cost-effectiveness of a pharmaceutical intervention programme in the context of primary care. Trial registration: NCT00794196

Effect of a governmentally-led physical activity program on motor skills in young children attending child care centers: a cluster randomized controlled trial.

OBJECTIVE: To assess the effect of a governmentally-led center based child care physical activity program (Youp'la Bouge) on child motor skills.Patients and methods: We conducted a single blinded cluster randomized controlled trial in 58 Swiss child care centers. Centers were randomly selected and 1:1 assigned to a control or intervention group. The intervention lasted from September 2009 to June 2010 and included training of the educators, adaptation of the child care built environment, parental involvement and daily physical activity. Motor skill was the primary outcome and body mass index (BMI), physical activity and quality of life secondary outcomes. The intervention implementation was also assessed. RESULTS: At baseline, 648 children present on the motor test day were included (age 3.3 +/- 0.6, BMI 16.3 +/- 1.3 kg/m2, 13.2% overweight, 49% girls) and 313 received the intervention. Relative to children in the control group (n = 201), children in the intervention group (n = 187) showed no significant increase in motor skills (delta of mean change (95% confidence interval: -0.2 (-0.8 to 0.3), p = 0.43) or in any of the secondary outcomes. Not all child care centers implemented all the intervention components. Within the intervention group, several predictors were positively associated with trial outcomes: 1) free-access to a movement space and parental information session for motor skills 2) highly motivated and trained educators for BMI 3) free-access to a movement space and purchase of mobile equipment for physical activity (all p < 0.05). CONCLUSION: This "real-life" physical activity program in child care centers confirms the complexity of implementing an intervention outside a study setting and identified potentially relevant predictors that could improve future programs.Trial registration: Trial registration number: clinical trials.gov NCT00967460 http://clinicaltrials.gov/ct2/show/NCT00967460.

Double blind controlled trial of D-penicillamine in patients with primary biliary cirrhosis.

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or hist

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: A multicenter randomized controlled trial.

Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes. Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n=78) or combined with EBL (Drug+EBL; n=80). HVPG measurements were performed at randomisation and after 4¿6 weeks on medical therapy. Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p=0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ¿20% or ¿12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL. Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders.

Does altering inclination alter effectiveness of treadmill training for gait impairment after stroke? A randomized controlled trial.

Objective: To assess whether a downhill walking training programme is more effective than the same amount of training applied uphill in chronic stroke survivors. Design: Randomized, single-blind study. Setting: Outpatient rehabilitation service. Methods: Thirty-eight adults with hemiplegia from stroke lasting more than three months were randomly allocated to one of the two groups: 'UP' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% ascending slope; and 'DOWN' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% descending slope. Both groups were treated 5 times a week for six weeks. Patients were evaluated before treatment, at the end of treatment and after three months. Outcome measures: Primary outcome measure was the number of patients showing an improvement in 6-minute walking test (6MWT) greater than 50 m. Secondary outcome measures were: (1) number of patients showing a clinically relevant improvement of gait speed during 10-m walking test (10mWT); (2) number of patients showing an improvement in timed up and go (TUG) greater than minimal detectable change. Results: Both groups had a significant improvement after treatment and at follow-up. At the end of treatment, compared to UP group, more patients in the DOWN group showed clinically significant improvements in primary and secondary outcomes (16/19 patients for 6MWT, 11/19 patients for 10mWT and 9/19 patients for TUG compared with 3/19, 4/19 and 2/19 patients, respectively, P < 0.01). At follow-up, results were similar except for 10mWT. Conclusions: In chronic stroke patients, downhill treadmill training produces a bigger effect than uphill training.

Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial.

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.

Motivational intervention to reduce cannabis use in young people with psychosis: a randomized controlled trial.

Background: Cannabis use has a negative impact on psychosis. Studies are needed to explore the efficacy of psychological interventions to reduce cannabis use in psychosis. Our aim is to study the efficacy of a specific motivational intervention on young cannabis users suffering from psychosis. Methods: Participants (aged less than 35 years) were randomly assigned to treatment as usual (TAU) alone, or treatment as usual plus motivational intervention (MI + TAU). TAU was comprehensive and included case management, early intervention and mobile team when needed. Assessments were completed at baseline and at 3, 6 and12 months follow-up. Results: Sixty-two participants (32 TAU and 30 MI + TAU) were included in the study. Cannabis use decreased in both groups at follow-up. Participants who received MI in addition to TAU displayed both a greater reduction in number of joints smoked per week and greater confidence to change cannabis use at 3 and 6 months follow-up, but differences between groups were nonsignificant at 12 months. Conclusions: MI is well accepted by patients suffering from psychosis and has a short-term impact on cannabis use when added to standard care. However, the differential effect was not maintained at 1-year follow-up. MI appears to be a useful active component to reduce cannabis use which should be integrated in routine clinical practice.

Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial.

BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.