Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing - a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites.

BACKGROUND: Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five. RESULTS: Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01). CONCLUSION: The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence. CLINICAL TRIAL REGISTRY INFORMATION: Protocol Record Identification Number: 132/03Registry URL: http://www.clinicaltrials.gov.

Influence of a lifestyle intervention in preschool children on physiological and psychological parameters (Ballabeina): study design of a cluster randomized controlled trial.

Childhood obesity and physical inactivity are increasing dramatically worldwide. Children of low socioeconomic status and/or children of migrant background are especially at risk. In general, the overall effectiveness of school-based programs on health-related outcomes has been disappointing. A special gap exists for younger children and in high risk groups. This paper describes the rationale, design, curriculum, and evaluation of a multicenter preschool randomized intervention study conducted in areas with a high migrant population in two out of 26 Swiss cantons. Twenty preschool classes in the German (canton St. Gallen) and another 20 in the French (canton Vaud) part of Switzerland were separately selected and randomized to an intervention and a control arm by the use of opaque envelopes. The multidisciplinary lifestyle intervention aimed to increase physical activity and sleep duration, to reinforce healthy nutrition and eating behaviour, and to reduce media use. According to the ecological model, it included children, their parents and the teachers. The regular teachers performed the majority of the intervention and were supported by a local health promoter. The intervention included physical activity lessons, adaptation of the built infrastructure; promotion of regional extracurricular physical activity; playful lessons about nutrition, media use and sleep, funny homework cards and information materials for teachers and parents. It lasted one school year. Baseline and post-intervention evaluations were performed in both arms. Primary outcome measures included BMI and aerobic fitness (20 m shuttle run test). Secondary outcomes included total (skinfolds, bioelectrical impedance) and central (waist circumference) body fat, motor abilities (obstacle course, static and dynamic balance), physical activity and sleep duration (accelerometry and questionnaires), nutritional behaviour and food intake, media use, quality of life and signs of hyperactivity (questionnaires), attention and spatial working memory ability (two validated tests). Researchers were blinded to group allocation. The purpose of this paper is to outline the design of a school-based multicenter cluster randomized, controlled trial aiming to reduce body mass index and to increase aerobic fitness in preschool children in culturally different parts of Switzerland with a high migrant population. Trial Registration: (clinicaltrials.gov) NCT00674544.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Comparing deep sclerectomy with collagen implant to the new method of very deep sclerectomy with collagen implant: a single-masked randomized controlled trial.

AIM: To prospectively study the intraocular pressure (IOP) lowering effect and safety of the new method of very deep sclerectomy with collagen implant (VDSCI) compared with standard deep sclerectomy with collagen implant (DSCI). METHODS: The trial involved 50 eyes of 48 patients with medically uncontrolled primary and secondary open-angle glaucoma, randomized to undergo either VDSCI procedure (25 eyes) or DSCI procedure (25 eyes). Follow-up examinations were performed before surgery and after surgery at day 1, at week 1, at months 1, 2, 3, 6, 9, 12, 18, and 24 months. Ultrasound biomicroscopy was performed at 3 and 12 months. RESULTS: Mean follow-up period was 18.6+/-5.9 (VDSCI) and 18.9+/-3.6 (DSCI) months (P=NS). Mean preoperative IOP was 22.4+/-7.4 mm Hg for VDSCI and 20.4+/-4.4 mm Hg for DSCI eyes (P=NS). Mean postoperative IOP was 3.9+/-2.3 (VDSCI) and 6.3+/-4.3 (DSCI) (P<0.05) at day 1, and 12.2+/-3.9 (VDSCI) and 13.3+/-3.4 (DSCI) (P=NS) at month 24. At the last visit, the complete success rate (defined as an IOP of < or =18 mm Hg and a percentage drop of at least 20%, achieved without medication) was 57% in VDSCI and 62% in DSCI eyes (P=NS) ultrasound biomicroscopy at 12 months showed a mean volume of the subconjunctival filtering bleb of 3.9+/-4.2 mm3 (VDSCI) and 6.8+/-7.5 mm3 (DSCI) (P=0.426) and 5.2+/-3.6 mm3 (VDSCI) and 5.4+/-2.9 mm3 (DSCI) (P=0.902) for the intrascleral space. CONCLUSIONS: Very deep sclerectomy seems to provide stable and good control of IOP at 2 years of follow-up with few postoperative complications similar to standard deep sclerectomy with the collagen implant.

Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial

OBJECTIVE To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. METHOD This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). RESULTS There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). CONCLUSION Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.

Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial.

Background/Objectives:To evaluate the impact of preoperative immunonutrition (IN) on postoperative morbidity in patients at risk of malnutrition undergoing major gastrointestinal (GI) surgery.Subjects/Methods:The combination of malnutrition and major GI surgery entails high morbidity. The Nutritional Risk Score (NRS) reliably identifies patients who need preoperative nutrition; the optimal nutritional formula for these patients still needs to be defined. In all, 152 patients with a NRS3 and undergoing elective major GI surgery were randomized between IN or isocaloric-isonitrogenous nutrition (ICN) given for 5 days preoperatively. Patients and caregivers were blinded for the allocated intervention. Thirty days complication rate was the primary endpoint. Infections, length of hospital stay and compliance were considered as secondary outcomes.Results:Overall, 145 patients were available for analysis; the 73 patients in the IN group matched well with the 72 ICN patients with regards to patient's and surgical characteristics. In all, 39 IN and 33 ICN patients experienced a total of 48 and 50 postoperative complications, respectively (P=0.723). Both groups did not differ significantly concerning infectious (13 vs 9) complications. Independent risk factors for overall complications were malignant disease (odds ratio (OR)=4.304; confidence interval (CI) 1.317-14.002) and operative time (OR=1.004; CI 1.000-1.008).Conclusion:In patients at nutritional risk, complications, infections and hospital stay after major GI surgery were comparable regardless of preoperative supplementation with IN or ICN.

Efficacy of brief motivational intervention at army conscription to address alcohol use and related problems: a randomized controlled trial

Objectives: The aim of this study was to evaluate the efficacy of brief motivational intervention (BMI) in reducing alcohol use and related problems among binge drinkers randomly selected from a census of 20 year-old French speaking Swiss men and to test the hypothesis that BMI contributes to maintain low-risk drinking among non-bingers. Methods: Randomized controlled trial comparing the impact of BMI on weekly alcohol use, frequency of binge drinking and occurrence of alcohol-related problems. Setting: Army recruitment center. Participants: A random sample of 622 men were asked to participate, 178 either refused, or missed appointment, or had to follow military assessment procedures instead, resulting in 418 men randomized into BMI or control conditions, 88.7% completing the 6-month follow-up assessment. Intervention: A single face-to-face BMI session exploring alcohol use and related problems in order to stimulate behaviour change perspective in a non-judgmental, empathic manner based on the principles of motivational interviewing (MI). Main outcome measures: Weekly alcohol use, binge drinking frequency and the occurrence of 12 alcohol-related consequences. Results: Among binge drinkers, we observed a 20% change in drinking induced by BMI, with a reduction in weekly drinking of 1.5 drink in the BMI group, compared to an increase of 0.8 drink per week in the control group (incidence rate ratio 0.8, 95% confidence interval 0,66 to 0,98, p = 0.03). BMI did not influence the frequency of binge drinking and the occurrence of 12 possible alcohol-related consequences. However, BMI induced a reduction in the alcohol use of participants who, after drinking over the past 12 months, experienced alcohol-related consequences, i.e., hangover (-20%), missed a class (-53%), got behind at school (-54%), argued with friends (-38%), engaged in unplanned sex (-45%) or did not use protection when having sex (-64%). BMI did not reduce weekly drinking in those who experienced the six other problems screened. Among non-bingers, BMI did not contribute to maintain low-risk drinking. Conclusions: At army conscription, BMI reduced alcohol use in binge drinkers, particularly in those who recently experienced alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is an interesting preventive option in young binge drinkers, particularly in countries with mandatory army recruitment.

Leptin and smoking cessation: secondary analyses of a randomized controlled trial assessing physical activity as an aid for smoking cessation.

BACKGROUND: Smokers have a lower body weight compared to non-smokers. Smoking cessation is associated with weight gain in most cases. A hormonal mechanism of action might be implicated in weight variations related to smoking, and leptin might be implicated. We made secondary analyses of an RCT, with a hypothesis-free exploratory approach to study the dynamic of leptin following smoking cessation. METHODS: We measured serum leptin levels among 271 sedentary smokers willing to quit who participated in a randomized controlled trial assessing a 9-week moderate-intensity physical activity intervention as an aid for smoking cessation. We adjusted leptin for body fat levels. We performed linear regressions to test for an association between leptin levels and the study group over time. RESULTS: One year after smoking cessation, the mean serum leptin change was +3.23 mg/l (SD 4.89) in the control group and +1.25 mg/l (SD 4.86) in the intervention group (p of the difference < 0.05). When adjusted for body fat levels, leptin was higher in the control group than in the intervention group (p of the difference < 0.01). The mean weight gain was +2.91 (SD 6.66) Kg in the intervention and +3.33 (SD 4.47) Kg in the control groups, respectively (p not significant). CONCLUSIONS: Serum leptin levels significantly increased after smoking cessation, in spite of substantial weight gain. The leptin dynamic might be different in chronic tobacco users who quit smoking, and physical activity might impact the dynamic of leptin in such a situation. CLINICAL TRIAL REGISTRATION NUMBER: NCT00521391.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: Ten-year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

Purpose/Objective(s): To analyze the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer compared with hyperfractionated radiotherapy alone.Materials/Methods: From July 1994 to July 2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiotherapy (median dose 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20mg/m2 for 5 consecutive days of weeks 1 and 5). The primary endpoint was time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to RTOG criteria. The trial was registered at the National Institutes of Health (www.clinicaltrials.gov; identifier number: NCT00002654).Results: Median follow-up was 9.5 years (range, 0.1 - 15.4 years). Median time to any treatment failure was not significantly different between treatment arms (p = 0.19). Locoregional control (p\0.05), distant metastasis-free survival (p = 0.02) and cancer specific survival (p = 0.03) were significantly improved in the combined treatment arm, with no difference in late toxicity between treatment arms. However, overall survival was not significantly different (p = 0.19). Conclusions: After long-term follow-up combined treatment with cisplatin and hyperfractionated, radiotherapy maintained an improved locoregional control, distant metastasis-free survival, and cancer specific survival as compared to hyperfractionated radiotherapy alone with no difference in late toxicity.Author Disclosure: P. Ghadjar, None; M. Simcock, None; G. Studer, None; A.S. Allal, None; M. Ozsahin, None; J. Bernier, None; M. To¨ pfer, None; F. Zimmermann, None; C. Glanzmann, None; D.M. Aebersold, None.

Impact of a board-game approach on current smokers: a randomized controlled trial.

ABSTRACT: BACKGROUND: The main objective of our study was to assess the impact of a board game on smoking status and smoking-related variables in current smokers. To accomplish this objective, we conducted a randomized controlled trial comparing the game group with a psychoeducation group and a waiting-list control group. METHODS: The following measures were performed at participant inclusion, as well as after a 2-week and a 3-month follow-up period: "Attitudes Towards Smoking Scale" (ATS-18), "Smoking Self-Efficacy Questionnaire" (SEQ-12), "Attitudes Towards Nicotine Replacement Therapy" scale (ANRT-12), number of cigarettes smoked per day, stages of change, quit attempts, and smoking status. Furthermore, participants were assessed for concurrent psychiatric disorders and for the severity of nicotine dependence with the Fagerström Test for Nicotine Dependence (FTND). RESULTS: A time × group effect was observed for subscales of the ANRT-12, ATS-18 and SEQ-12, as well as for the number of cigarettes smoked per day. At three months follow-up, compared to the participants allocated to the waiting list group, those on Pick-Klop group were less likely to remain smoker.Outcomes at 3 months were not predicted by gender, age, FTND, stage of change, or psychiatric disorders at inclusion. CONCLUSIONS: The board game seems to be a good option for smokers. The game led to improvements in variables known to predict quitting in smokers. Furthermore, it increased smoking-cessation rates at 3-months follow-up. The game is also an interesting alternative for smokers in the precontemplation stage.