A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers

Background

Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM) is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids.

Methods and Results

On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet), morphine (40 mg immediate release tablet) or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus) but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9%) at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2%) at 120-150 min after drug intake (p = 0.001). No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6%) at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9%) at 120-150 min after drug intake (p = 0.60).

Conclusions

Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol’s main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic stimulation on descending controls.

Trial Registration

Netherlands Trial Register NTR2716     

Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974

Background

Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial.

Methods

Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% withanolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention.

Results

Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group.

Relevance

Many patients seek alternatives and/or complementary care to conventional anxiety treatments. To date, no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety. Knowledge of the efficacy, safety or risk of natural health products, and naturopathic treatments is important for physicians and the public in order to make informed decisions.

Interpretation

Both NC and PT led to significant improvements in patients'' anxiety. Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group. Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT. The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect.

Trial Registration

Controlled-Trials.com ISRCTN78958974     

Well-Loved Music Robustly Relieves Pain: A Randomized,Controlled Trial

Music has pain-relieving effects, but its mechanisms remain unclear. We sought to verify previously studied analgesic components and further elucidate the underpinnings of music analgesia. Using a well-characterized conditioning-enhanced placebo model, we examined whether boosting expectations would enhance or interfere with analgesia from strongly preferred music. A two-session experiment was performed with 48 healthy, pain experiment-naïve participants. In a first cohort, 36 were randomized into 3 treatment groups, including music enhanced with positive expectancy, non-musical sound enhanced with positive expectancy, and no expectancy enhancement. A separate replication cohort of 12 participants received only expectancy-enhanced music following the main experiment to verify the results of expectancy-manipulation on music. Primary outcome measures included the change in subjective pain ratings to calibrated experimental noxious heat stimuli, as well as changes in treatment expectations. Without conditioning, expectations were strongly in favor of music compared to non-musical sound. While measured expectations were enhanced by conditioning, this failed to affect either music or sound analgesia significantly. Strongly preferred music on its own was as pain relieving as conditioning-enhanced strongly preferred music, and more analgesic than enhanced sound. Our results demonstrate the pain-relieving power of personal music even over enhanced expectations.

Trial Information

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01835275","term_id":"NCT01835275"}}NCT01835275.     

The Effectiveness of Pregabalin for Post-Tonsillectomy Pain Control: A Randomized Controlled Trial

BackgroundAlthough various analgesics have been used, postoperative pain remains one of the most troublesome aspects of tonsillectomy for patients.ObjectiveThe aim of the present study was to evaluate the effectiveness of premedication using pregabalin compared with placebo (diazepam) on postoperative pain control in patients undergoing tonsillectomy.MethodsForty-eight adult patients were randomly divided into a control group and a pregabalin group. Preoperatively, patients in the control group received 4 mg diazepam orally as placebo, whereas those in the pregabalin group received 300 mg pregabalin orally. All participants were provided with patient-controlled analgesia using fentanyl for 24 hours after surgery. Postoperative pain treatment included acetaminophen 650 mg three times daily for 8 postoperative days. The primary outcome measure was the total amount of patient-controlled fentanyl consumption after tonsillectomy. Secondary outcome measures were the number of injections of ketorolac tromethamine (each 30 mg) requested by patients, pain scores, overall satisfaction scores, drowsiness, nausea, dizziness, headache, and vomiting after the surgery. P < 0.05 was considered statistically significant.ResultsThe total amount of fentanyl demanded decreased significantly in the pregabalin group (P < 0.001). There were no significant differences in the number of ketorolac tromethamine injections, pain scores, overall satisfaction scores, drowsiness, nausea, dizziness, headache, and vomiting between the two groups.ConclusionAdministration of 300 mg pregabalin prior to tonsillectomy decreases fentanyl consumption compared with that after 4 mg diazepam, without an increased incidence of adverse effects.

Trial Registration

KCT0001215     

Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial

Aims

Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration.

Materials and Methods

The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance.

Results

GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups.

Conclusions

Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback.

Trial Registration

ClinicalTrials.gov NCT01146288     

Internet-Delivered Cognitive-Behavioral Therapy for Social Anxiety Disorder in Romania: A Randomized Controlled Trial

MethodsParticipants (n = 76) were recruited, screened and randomized to either a nine-week guided iCBT or a wait-list control group in April and May 2012. Self-report measures were collected before (April 2012) and after the intervention (July 2012), as well as six months later (January 2013). Although social anxiety was assessed with multiple measures, the Liebowitz Social Anxiety Scale - Self Report version (LSAS-SR) and Social Phobia Inventory (SPIN) were used as the primary outcome measures.ResultsA significant difference with a large between-group effect size in favor of iCBT was found (Cohen´s d = 1.19 for LSAS-SR and d = 1.27 for SPIN). Recovery rates show that 36.8% (n = 14) in the treatment group score below the SPIN clinical cut-off compared to only 2.6% (n = 1) in the wait-list control group. Post-intervention clinical interviews also revealed that 34.2% (n = 13) of the treatment group was completely recovered (full remission) while additionally 36.8% (n = 14) retained some social anxiety symptoms (partial remission). However, an important study limitation is that post-intervention interviewers were not blinded to the study conditions. The program also effectively reduced depression and dysfunctional thinking (between-group Cohen´s d = 0.84 for depression and d = 0.63 for dysfunctional thinking). Moreover, the iCBT intervention appears to have a long-term impact for participants’ functioning, as the treatment gains were maintained six months later.ConclusionsInternet-delivered interventions display a high potential to quickly and widely disseminate effective evidence-based programs around the world. This study provides support for guided iCBT as a promising treatment approach in Romania.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01557894","term_id":"NCT01557894"}}NCT01557894     

A Phase II,Randomized, Double-Blind,Placebo Controlled,Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects

Background

Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.

Objective

The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.

Methods

Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis.

Results

Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R² = 0.492 for HPT, R² = 0.538 for PPT, R² = 0.558 for HPTo and R² = 0.584 for PPTo).

Conclusions

The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre.     

Internet Treatment for Generalized Anxiety Disorder: A Randomized Controlled Trial Comparing Clinician vs. Technician Assistance

Background

Internet-based cognitive behavioural therapy (iCBT) for generalized anxiety disorder (GAD) has been shown to be effective when guided by a clinician. The present study sought to replicate this finding, and determine whether support from a technician is as effective as guidance from a clinician.

Method

Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program and 150 participants with GAD were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 10 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Penn State Worry Questionnaire (PSWQ) and the Generalized Anxiety Disorder-7 Item (GAD-7). Completion rates were high, and both treatment groups reduced scores on the PSWQ (p<0.001) and GAD-7 (p<0.001) compared to the delayed treatment group, but did not differ from each other. Within group effect sizes on the PSWQ were 1.16 and 1.07 for the clinician- and technician-assisted groups, respectively, and on the GAD-7 were 1.55 and 1.73, respectively. At 3 month follow-up participants in both treatment groups had sustained the gains made at post-treatment. Participants in the clinician-assisted group had made further gains on the PSWQ. Approximately 81 minutes of clinician time and 75 minutes of technician time were required per participant during the 10 week treatment program.

Conclusions

Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment/control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD. This form of treatment has potential to increase the capacity of existing mental health services.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12609000563268     

A Randomized Controlled Trial to Test the Effectiveness of an Immersive 3D Video Game for Anxiety Prevention among Adolescents

Adolescent anxiety is debilitating, the most frequently diagnosed adolescent mental health problem, and leads to substantial long-term problems. A randomized controlled trial (n = 138) was conducted to test the effectiveness of a biofeedback video game (Dojo) for adolescents with elevated levels of anxiety. Adolescents (11–15 years old) were randomly assigned to play Dojo or a control game (Rayman 2: The Great Escape). Initial screening for anxiety was done on 1,347 adolescents in five high schools; only adolescents who scored above the “at-risk” cut-off on the Spence Children Anxiety Survey were eligible. Adolescents’ anxiety levels were assessed at pre-test, post-test, and at three month follow-up to examine the extent to which playing Dojo decreased adolescents’ anxiety. The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition. Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms (not of total anxiety symptoms) in the Dojo condition compared to the control condition. Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes. The present results are of importance for prevention science, as this was the first full-scale randomized controlled trial testing indicated prevention effects of a video game aimed at reducing anxiety. Future research should carefully consider the choice of control condition and outcome measurements, address the potentially high impact of participants’ expectations, and take critical design issues into consideration, such as individual- versus group-based intervention and contamination issues.     

帕利哌酮和奥氮平在急性期精神分裂症的随机对照研究

目的:研究帕利哌酮治疗急性期精神分裂症的疗效和安全性.方法:94例符合国际疾病分类第10版(ICD-10)诊断标准的精神分裂症急性期患者随机分为帕利哌酮组(N=45)和奥氮平组(N=49),采用简明精神病量表(the Brief Psychiatric Rating Scale,BPRS)、阳性和阴性症状量表(the Positive and Negative Syndrome Scale,PANSS)及个人和社会功能量表(Personal and Social Performance Scale,PSP)评定疗效,采用治疗中需处理的不良反应症状量表(Treatment Emergent Symptoms Scale,TESS)评定安全性.结果:两组治疗后BPRS和PANSS评分均低于治疗前,帕利哌酮组BPRS评分(23.15± 4.12)vs.(47.45± 3.87),PANSS评分(51.06± 6.87)vs.(87.96± 4.16),P＜0.05;奥氮平组BPRS评分(26.96± 4.30)vs.(45.11±3.18),PANSS评分(58.42± 5.72)vs.(84.71± 10.31),P＜0.05;治疗后,帕利哌酮组BPRS、PANSS评分低于奥氮平组,但差异无统计学意义(P＞o.05).两组治疗后PSP评分均优于治疗前,且帕利哌酮组效果较奥氮平组效果更好(P＜0.05).两组TESS评分在治疗后差异无统计学意义(P＞0.05).结论:帕利哌酮治疗急性期精神分裂症疗效,安全性较高,是一种值得借鉴的策略.     

A Randomized Controlled Trial of Storytelling as a Communication Tool

Introduction

Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup.

Methods

Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution.

Results

There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement “I would go for the same choice if I had to do it over again”. The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups.

Conclusions

Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes.

Trial Registration

Current Controlled Trials, ISRCTN39642997 (http://www.controlled-trials.com/ISRCTN39642997)     

The Effects of Aroma Foot Massage on Blood Pressure and Anxiety in Japanese Community-Dwelling Men and Women: A Crossover Randomized Controlled Trial

Objectives

The aim of this study was to investigate the effects of aroma foot massage on blood pressure, anxiety, and health-related quality of life (QOL) in Japanese community-dwelling men and women using a crossover randomized controlled trial.

Methods

Fifty-seven eligible participants (5 men and 52 women) aged 27 to 72 were randomly divided into 2 intervention groups (group A: n = 29; group B: n = 28) to participate in aroma foot massages 12 times during the 4-week intervention period. Systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate, state anxiety, and health-related QOL were measured at the baseline, 4-week follow-up, and 8-week follow-up. The effects of the aroma foot massage intervention on these factors and the proportion of participants with anxiety were analyzed using a linear mixed-effect model for a crossover design adjusted for participant and period effects. Furthermore, the relationship between the changes in SBP and state anxiety among participants with relieved anxiety was assessed using a linear regression model.

Results

Aroma foot massage significantly decreased the mean SBP (p = 0.02), DBP (p = 0.006), and state anxiety (p = 0.003) as well as the proportion of participants with anxiety (p = 0.003). Although it was not statistically significant (p = 0.088), aroma foot massage also increased the score of mental health-related QOL. The change in SBP had a significant and positive correlation with the change in state anxiety (p = 0.01) among participants with relieved anxiety.

Conclusion

The self-administered aroma foot massage intervention significantly decreased the mean SBP and DBP as well as the state anxiety score, and tended to increase the mental health-related QOL scores. The results suggest that aroma foot massage may be an easy and effective way to improve mental health and blood pressure.

Trial Registration

University Hospital Medical Information Network 000014260     

不同剂量的地佐辛对预防女性丙泊酚注射痛的随机对照研究

目的:观察预注不同剂量的地佐辛在预防女性丙泊酚注射痛中的镇痛效应,寻找地佐辛的适宜剂量。方法:本研究为随机对照研究,选择ASAⅠ-Ⅱ级行择期宫腔镜手术的女性患者200例,采用计算机随机数字法分为四组。C组(n=39):预先注射生理盐水;D1组(n=50):预先注射地佐辛0.025 mg/kg;D2组(n=55):预先注射地佐辛0.05 mg/kg;D3组(n=56):预先注射地佐辛0.1mg/kg,所有预注药物均稀释至5 m L,注药时间均为10 s,并于注药后2 min采用TCI泵1 m L/s的速度推注2 mg/kg丙泊酚。记录患者预注药物前后SBP、DBP、HR、Sp O_2及不良反应;注射丙泊酚的过程中反复询问疼痛情况,采用Ambesh四点评分法行注射疼痛评分。结果:D2组、D3组丙泊酚注射痛发生率均显著低于C组(P0.05),D1组与C组比较无统计学差异(P0.05),D2组与D3组比较无统计学差异(P0.05)。D3组眩晕、嗜睡的发生率明显高于D1组和D2组(P0.05)。结论:地佐辛能有效降低女性丙泊酚注射痛的发生率和严重程度,降低注射痛的适宜剂量为0.05 mg/kg。     

The Effect of VoorZorg,the Dutch Nurse-Family Partnership,on Child Maltreatment and Development: A Randomized Controlled Trial

Background

Child maltreatment is a great public health concern that has long-term mental and physical health consequences and can result in death. We studied the effect of a nurse home visiting program on child maltreatment among young disadvantaged families in the Netherlands. This study is the first to investigate the effects of this program outside of the United States.

Methods

We conducted a single blind, parallel-group, randomized controlled trial that compared usual care with the nurse home visitation program, which began during pregnancy and continued until the children’s second birthdays, in 460 disadvantaged women who were pregnant for the first time and <26 years of age. The primary outcome was the existence of a report about the child from a child protecting services agency (CPS reports). Secondary outcome measures included home environment and child behavior.

Results

Two hundred twenty-three participants were assigned to the control group, and 237 were assigned to the intervention group. Three years after birth, 19% of the children in the control group had a CPS report. The 11 percent of children in the intervention group with CPS files was significantly lower (relative risk 0.91, p-value 0.04). At 24 months, the intervention group scored significantly better on the IT-HOME. At 24 months after birth, the children in the intervention group exhibited a significant improvement in internalizing behavior (relative risk 0.56, p-value 0.04) but no evidence of a difference from the control group in externalizing behavior (relative risk 0.71, p-value 0.12).

Conclusion

The number of CPS reports for the intervention group was significantly lower than that of the control group. Additionally, the long-term home environments were improved and internalizing behaviors of the children were lower in the intervention group.

Trial Registration

Dutch Trial Register NTR854     

A Randomized Controlled Trial of a Commercial Internet Weight Loss Program

Objective: To assess, in a 1‐year randomized controlled trial, the efficacy of eDiets.com (a commercial Internet weight loss program) in improving weight, cardiovascular health, and quality of life. Research Methods and Procedures: Participants were 47 women with a mean age of 43.7 ± 10.2 (SD) years and a mean BMI of 33.5 ± 3.1 kg/m². They were randomly assigned to either: 1) eDiets.com , a commercial Internet‐based program available to the public; or 2) a weight loss manual (i.e., LEARN Program for Weight Control 2000). At baseline, participants in both groups met briefly with a psychologist who instructed them to follow the components of their program as closely as possible. Additional brief visits were provided at weeks 8, 16, 26, and 52 to review their progress. Change in weight was the main outcome measure. Results: At week 16, participants in eDiets.com lost 0.9 ± 3.2% of initial weight compared with 3.6 ± 4.0% for women assigned to the weight loss manual. At week 52, losses increased to 1.1 ± 4.0% and 4.0 ± 5.1%, respectively. Results of a last‐observation‐carried‐forward analysis found that women in the manual group lost significantly (p < 0.05) more weight (at both times) than those treated by eDiets.com . (Results, however, of baseline‐carried‐forward and completers analyses did not reach statistical significance.) There were no significant differences between groups in changes in cardiovascular risk factors or quality of life. Discussion: This study provides consumers with important information about the probable benefits they can expect from participating in a popular Internet‐based weight loss program.     

A Multicenter,Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

BackgroundDespite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes.ResultsA total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention.ConclusionsOsteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants.