Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a partially randomized controlled trial (preference trial).

BACKGROUND Drugs for inhalation are the cornerstone of therapy in obstructive lung disease. We have observed that up to 75 % of patients do not perform a correct inhalation technique. The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction. The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers. The participants will be divided into two groups and five arms. The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms. In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study. In the randomized group the three arms comprise: intervention A, intervention B and a control arm. Intervention A is written information (a leaflet describing the correct inhalation techniques). Intervention B is written information about inhalation techniques plus training by an instructor. Every patient in each group will be visited six times during the year of the study at health care center. DISCUSSION Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice.

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study.

Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.

Effectiveness of two interventions based on improving patient-practitioner communication on diabetes self-management in patients with low educational level: study protocol of a clustered randomized trial in primary care.

BACKGROUND In the last decades the presence of social inequalities in diabetes care has been observed in multiple countries, including Spain. These inequalities have been at least partially attributed to differences in diabetes self-management behaviours. Communication problems during medical consultations occur more frequently to patients with a lower educational level. The purpose of this cluster randomized trial is to determine whether an intervention implemented in a General Surgery, based in improving patient-provider communication, results in a better diabetes self-management in patients with lower educational level. A secondary objective is to assess whether telephone reinforcement enhances the effect of such intervention. We report the design and implementation of this on-going study. METHODS/DESIGN The study is being conducted in a General Practice located in a deprived neighbourhood of Granada, Spain. Diabetic patients 18 years old or older with a low educational level and inadequate glycaemic control (HbA1c > 7%) were recruited. General Practitioners (GPs) were randomised to three groups: intervention A, intervention B and control group. GPs allocated to intervention groups A and B received training in communication skills and are providing graphic feedback about glycosylated haemoglobin levels. Patients whose GPs were allocated to group B are additionally receiving telephone reinforcement whereas patients from the control group are receiving usual care. The described interventions are being conducted during 7 consecutive medical visits which are scheduled every three months. The main outcome measure will be HbA1c; blood pressure, lipidemia, body mass index and waist circumference will be considered as secondary outcome measures. Statistical analysis to evaluate the effectiveness of the interventions will include multilevel regression analysis with three hierarchical levels: medical visit level, patient level and GP level. DISCUSSION The results of this study will provide new knowledge about possible strategies to promote a better diabetes self-management in a particularly vulnerable group. If effective, this low cost intervention will have the potential to be easily incorporated into routine clinical practice, contributing to decrease health inequalities in diabetic patients. TRIAL REGISTRATION Clinical Trials U.S. National Institutes of Health, NCT01849731.

Physical activity, bodyweight, health and fear of negative evaluation in primary school children.

Fear of negative evaluation (FNE) is regarded as being the core feature of social anxiety. The present study examined how FNE is associated with physical activity (PA), body mass index (BMI) and perceived physical health (PPH) in children. Data were collected in a sample of 502 primary school children in first and fifth grades taking part in a randomized-controlled trial ("Kinder-Sportstudie KISS") aimed at increasing PA and health. PA was assessed by accelerometry over 7 days, PPH by the Child Health Questionnaire and FNE by the Social Anxiety Scale for Children--Revised. BMI z-scores were calculated based on Swiss norms. Cross-sectional analyses indicated that children high in FNE exercised less, reported lower levels of PPH and had higher BMI z-scores (P<0.01). Using mixed linear models, the school-based PA intervention did not manage to reduce FNE scores. Overweight children demonstrated a greater increase in FNE (P<0.05) indicating that enhanced weight may be a risk factor for FNE. In conclusion, the associations among high FNE, low PA and increased BMI should be considered when promoting an active lifestyle in children.

Effects of a lifestyle intervention on adiposity and fitness in overweight or low fit preschoolers (Ballabeina).

OBJECTIVE: Overweight (OW) and low fit children represent cardiovascular high-risk groups. A multidimensional school-based lifestyle intervention performed in 652 preschoolers reduced skinfold thickness and waist circumference, and improved fitness, but did not affect BMI. The objective of this study is to examine whether the intervention was equally effective in OW (≥90th national percentile) and/or low fit (lowest sex- and age-adjusted quartile of aerobic fitness) children compared to their normal weight and normal fit counterparts. DESIGN AND METHODS: Cluster randomized controlled single blinded trial, conducted in 2008/09 in 40 randomly selected preschool classes in Switzerland. The intervention included a playful physical activity program and lessons on nutrition, media use and sleeps. Primary outcomes were BMI and aerobic fitness; secondary outcomes included sum of four skinfolds, waist circumference and motor agility. Modification of intervention effects by BMI-group and fitness-group was tested by interaction terms. RESULTS: Compared to their counterparts, OW children (n = 130) had more beneficial effects on waist circumference (p for interaction = 0.001) and low fit children (n = 154) more beneficial effects on all adiposity outcomes (p for interaction ≤0.03). The intervention effects on both fitness outcomes were not modified by BMI- or fitness-group (all p for interaction ≥0.2). Average intervention effect sizes for BMI were -0.12, -0.05, -0.26 and -0.02 kg/m(2) and for aerobic fitness were 0.40, 0.30, 0.12 and 0.36 stages for OW, normal weight, low fit and normal fit children, respectively. Conclusions: This multidimensional intervention was equally and for some adiposity measures even more effective in high-risk preschoolers and represents a promising option for these children.

Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with estrogen receptor-positive, HER-2-positive advanced breast cancer: a proof-of-concept trial (SAKK 23/03).

A sequential treatment design was chosen in this trial to ensure complete resistance to single-agent non-steroidal aromatase inhibitor (AI) and trastuzumab both given as monotherapy before receiving the combination of a non-steroidal AI and trastuzumab. Key eligibility criteria included postmenopausal patients with advanced, measurable, human epidermal growth factor receptor-2 (HER-2)-positive disease (assessed by FISH, ratio (≥2)), hormone receptor (HR)-positive disease, and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in the adjuvant or in the advanced setting. Patients received standard dose trastuzumab monotherapy in step 1 and upon disease progression continued trastuzumab in combination with letrozole in step 2. The primary endpoint was clinical benefit rate (CBR) in step 2. Totally, 13 patients were enrolled. In step 1, six patients (46%) achieved CBR. Median time to progression (TTP) was 161 days (95% confidence interval (CI): 82-281). In step 2, CBR was observed in eight out of the 11 evaluable patients (73%), including one patient with partial response. Median TTP for all the 11 patients was 188 days (95% CI: 77-not reached). Results of this proof-of-concept trial suggest that complete resistance to both AI and trastuzumab can be overcome in a proportion of patients by combined treatment of AI and trastuzumab, as all patients served as their own control. Our results appear promising for a new treatment strategy that offers a chemotherapy-free option for at least a subset of patients with HR-positive, HER-2-positive breast cancer over a clinically relevant time period.

High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: a randomized clinical trial.

The health benefits associated with the consumption of polyphenol-rich foods have been studied in depth, however, the full mechanism of action remains unknown. One of the proposed mechanisms is through microbiota interaction. In the present study, we aimed to explore the relationship between changes in fecal microbiota and changes in urinary phenolic metabolites after wine interventions. Nine participants followed a randomized, crossover, controlled interventional trial. After the washout period, they received red wine, dealcoholized red wine or gin for 20 days each. Polyphenol metabolites (n > 60) in urine were identified and quantified by UPLC-MS/MS and the microbial content of fecal samples was quantified by real-time quantitative PCR. Interventions with both red wine and dealcoholized red wine increased the fecal concentration of Bifidobacterium, Enterococcus and Eggerthella lenta, compared to gin intervention and baseline. When participants were categorized in tertiles of changes in fecal bacteria, those in the highest tertile of Bifidobacteria had higher urinary concentration changes in syringic acid, p-coumaric acid, 4-hydroxybenzoic acid and homovanillic acid (all anthocyanin metabolites) than those in tertile 1 (P < 0.05, all). In addition, changes of Bifidobacteria correlated positively with changes of these metabolites (r = 0.5-0.7, P < 0.05, all). Finally, the 68.5% changes in Bifidobacteria can be predicted by syringic acid and 4-hydroxybenzoic acid changes. This study confirms the important role of polyphenols as bacterial substrates and their modulatory capacity as an important field in the research of new products with prebiotic and probiotic characteristics for the food industry.

Prevention of major depression in complex medically ill patients: preliminary results from a randomized, controlled trial.

BACKGROUND: Depression is highly prevalent in patients with physical illness and is associated with a diminished quality of life and poorer medical outcomes. OBJECTIVE: The authors evaluated whether a multifaceted intervention conducted by a psychiatric consultation-liaison nurse could reduce the incidence of major depression in rheumatology inpatients and diabetes outpatients with a high level of case complexity. METHOD: Of 247 randomized patients, the authors identified 100 patients with a high level of case complexity at baseline and without major depression (65 rheumatology and 35 diabetes patients). Patients were randomized to usual care (N=53) or to a nurse-led intervention (N=47). Main outcomes were the incidence of major depression and severity of depressive symptoms during a 1-year follow-up, based on quarterly assessments with standardized psychiatric interviews. RESULTS: The incidence of major depression was 63% in usual-care patients and 36% in the intervention group. Effects of intervention on depressive symptoms were observed in outpatients with diabetes but not in rheumatology inpatients. CONCLUSION: These preliminary results based on subgroup analysis suggest that a multifaceted nurse-led intervention may prevent the occurrence of major depression in complex medically ill patients and reduce depressive symptoms in diabetes outpatients.

Correcting non cephalic presentation with moxibustion: study protocol for a multi-centre randomised controlled trial in general practice.

BACKGROUND Non cephalic presentation in childbirth involves various risks to both the mother and the foetus. The incidence in Spain is 3.8% of all full-term pregnancies. The most common technique used to end the gestation in cases of non cephalic presentation is that of caesarian section, and although it provokes a lower rate of morbi-mortality than does vaginal delivery in such situations, there remains the possibility of traumatic injury to the foetal head and neck, while maternal morbidity is also increased. The application of heat (moxibustion) to an acupuncture point, in order to correct non cephalic presentation, has been practised in China since ancient times, but as yet there is insufficient evidence of its real effectiveness. METHODS/DESIGN The experimental design consists of a multi-centre randomised controlled trial with three parallel arms, used to compare real moxibustion, sham moxibustion and the natural course of events, among pregnant women with a non cephalic presentation and a gestational duration of 33-35 weeks (estimated by echography). The participants in the trial will be blinded to both interventions. The results obtained will be analyzed by professionals, blinded with respect to the allocation to the different types of intervention. In addition, we intend to carry out a economic analysis. DISCUSSION This trial will contribute to the development of evidence concerning moxibustion in the correction of non cephalic presentations. The primary outcome variable is the proportion of cephalic presentations at term. As secondary outcomes, we will evaluate the proportion of cephalic presentations at week 38 of gestation, determined by echography, together with the safety of the technique, the specificity of moxibustion and the control of the blinding process. This study has been funded by the Health Ministry of the Andalusian Regional Government. TRIAL REGISTRATION Current Controlled Trials ISRCTN10634508.

Chest physiotherapy using passive expiratory techniques does not reduce bronchiolitis severity: a randomised controlled trial.

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children <1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties (P = 0.044). Complications were rare but occurred more frequently, although not significantly (P = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients.

Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome.

Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS). Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject's dominant leg was measured for straight leg raise (SLR) range of motion (ROM) before and after interventions. Data were analyzed with a 3 × 2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested.

Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

PURPOSE: Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. MATERIALS AND METHODS: RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). RESULTS: Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). CONCLUSION: Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue.

Swiss Interdisciplinary Management Programme for Heart Failure (SWIM-HF): a randomised controlled trial study of an outpatient inter-professional management programme for heart failure patients in Switzerland.

PRINCIPLES: International guidelines for heart failure (HF) care recommend the implementation of inter-professional disease management programmes. To date, no such programme has been tested in Switzerland. The aim of this randomised controlled trial (RCT) was to test the effect on hospitalisation, mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerland.METHODS: Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF. A total of 42 eligible patients were randomised to an intervention (n = 22) or usual care group (n = 20). Medical treatment was optimised and lifestyle recommendations were given to all patients. Intervention patients additionally received a home visit by a HF-nurse, followed by 17 telephone calls of decreasing frequency over 12 months, focusing on self-care. Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care. Data were collected at baseline, 3, 6, 9 and 12 months. Mixed regression analysis (quality of life) was used. Outcome assessment was conducted by researchers blinded to group assignment.RESULTS: After 12 months, 22 (52%) patients had an all-cause re-admission or died. Only 3 patients were hospitalised with HF decompensation. No significant effect of the intervention was found on HF related to quality of life.CONCLUSIONS: An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies.

What process research tells us about brief intervention efficacy.

ISSUE: This article explores mechanisms of the efficacy of brief intervention (BI). APPROACH: We conducted a BI trial at the emergency department of the Lausanne University Hospital, of whom 987 at-risk drinkers were randomised into BI and control groups. The overall results demonstrated a general decrease in alcohol use with no differences across groups. The intention to change was explored among 367 patients who completed BI. Analyses of 97 consecutive tape-recorded sessions explored patient and counsellor talks during BI, and their relationship to alcohol use outcome. KEY FINDINGS: Evaluation of the articulation between counsellor behaviours and patient language revealed a robust relationship between counsellor motivational interviewing (MI) skills and patient change talk during the intervention. Further exploration suggested that communication characteristics of patients during BI predicted changes in alcohol consumption 12 months later. Moreover, despite systematic training, important differences in counsellor performance were highlighted. Counsellors who had superior MI skills achieved better outcomes overall, and maintained efficacy across all levels of patient ability to change, whereas counsellors with inferior MI skills were effective mostly with patients who had higher levels of ability to change. Finally, the descriptions of change talk trajectories within BI and their association with drinking 12 months later showed that final states differed from initial states, suggesting an impact resulting from the progression of change talk during the course of the intervention. IMPLICATION: These findings suggest that BI should focus on the general MI attitude of counsellors who are capable of eliciting beneficial change talk from patients. [Daeppen J-B, Bertholet N, Gaume J. What process research tells us about brief intervention efficacy.

Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952.

S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients. 211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36 months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination. At first measurement, 178 patients had S100B values <0.2 μg/l and 33 ≥ 0.2 μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (≥ 0.2 μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B ≥ 0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P < 0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50-10.16). Similar results were observed regarding overall survival (OS). Serial determination of S100B in stage IIb-III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B ≥ 0.2 μg/l is more pronounced in stage III disease compared with stage IIb.