Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial

Background

The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).

Methods

Twelve CRT patients with non-ischemic heart failure (NYHA class II–III) were enrolled in a randomized, double-blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD-80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity by microneurography (MSNA), peak oxygen consumption (pVO₂), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL.

Results

DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac cycles vs. 64±14 bursts/100 cardiac cycles, p<0.05). The mean pVO₂ increased non-significantly from 15.6±6 mL/min/kg during DDD-60 to 16.7±6 mL/min/kg during DDD-80, and p-NT-proBNP remained unchanged. The QoL score indicated that DDD-60 was better tolerated.

Conclusion

In CRT patients with non-ischemic heart failure, 3 months of DDD-80 pacing decreased sympathetic outflow (burst incidence only) compared to DDD-60 pacing. However, Qol scores were better during the lower pacing rate. Further and larger scale investigations are indicated.

Trial Registration

ClinicalTrials.gov NCT02258061     

Intravenous Immunoglobulin for Hypogammaglobulinemia after Lung Transplantation: A Randomized Crossover Trial

Background

We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG) after lung transplantation.

Methods

We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG), 10% Purified (Gamunex, Bayer, Elkhart, IN) monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG). The primary outcome was the number of bacterial infections within each treatment period.

Results

IVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24). There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001). Four serious adverse events (resulting in hospitalization) occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37). Chills, flushing, and nausea occurred during one infusion of IVIG.

Conclusions

Treatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00115778","term_id":"NCT00115778"}}NCT00115778     

Caffeine Intake,Short Bouts of Physical Activity,and Energy Expenditure: A Double-Blind Randomized Crossover Trial

PA energy expenditure (PAEE) is the most variable component of Total Energy Expenditure (TEE) and largely due to the balance of sedentary time (SedT) and low intensity physical activity (LIPA). There has been an emergence for seeking an understanding of factors which determine variations in SedT, LIPA, and PAEE. Sedentary behavior and physical activity are relatively resistant to change by experimental dietary treatments and significant body weight changes. Although caffeine (Caf) is by far the most heavily used nutritional agent ingested to promote a sense of vigor/alertness, it is still unknown if Caf is effective in increasing PAEE and physical activity. The aim of the study was to test the hypothesis that 2 daily doses of Caf (as a capsule to blind the treatment and divided equally during breakfast and lunch) increase PAEE and TEE, and it would do so through increasing the frequent and brief bouts of physical activity (~1-5 min long) through the day as measured by accelerometry. In 21 low Caf users (<100 mg day^-1), we used a double-blind crossover trial (ClinicalTrials.govID;{"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294) with two conditions (4-day each with a 3-day washout period) randomly ordered as 5 mg kg^-1 day^-1 of Caf and maltodextrin as placebo (Plc). Resting energy expenditure (REE) by indirect calorimetry, total energy expenditure (TEE) from doubly labeled water, PAEE calculated as TEE-(REE+0.1TEE), and accelerometry measurements of both LIPA and MVPA were not different between conditions. However, regardless of caffeine or placebo, there were several significant relationships between brief bouts of LIPA and MVPA with PAEE. In conclusion, this double-blind study found that low and moderate-vigorous activity as well as the total volume of PAEE in free-living conditions is resistant to dietary caffeine intake that was equivalent to 5 cups of espresso or 7 cups of tea.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294     

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     

Suture Closure versus Non-Closure of Subcutaneous Fat and Cosmetic Outcome after Cesarean Section: A Randomized Controlled Trial

Introduction

To investigate the effect of subcutaneous fat suture closure versus non-closure at cesarean section (CS) on long-term cosmetic outcome.

Material and Methods

Women undergoing planned or unplanned CS were randomized to either subcutaneous fat suture closure or non-closure using a 1∶1 allocation algorithm. Participants and outcome assessors were blinded to group allocation. Scar evaluation was performed after two and six months. Primary outcome measures were Patient and Observer Scar Assessment Scale (POSAS) summary scores six months after surgery. Secondary outcome measures were Vancouver Scar Scale (VSS) summary scores, retraction of the scar below the level of the surrounding skin, duration of surgery, and development of hematoma, seroma, surgical site infection (SSI) or wound disruption. Data were analyzed according to the intention to treat principle.

Results

A total of 116 women were randomized and 91 participants, 47 in the closure and 44 in the non-closure group, completed the trial and were analyzed. There were no differences in patient morphometrics or surgery indications between groups. At two and six months no significant differences were found with respect to POSAS or VSS scores between groups. After two months significantly more women in the non-closure group described their scar as being retracted below the level of the skin (36% vs. 15%, p = 0.02) whereas no difference was observed at six months. There were significantly more hematomas in the non-closure (25%) compared to the closure group (4%) (p = 0.005). There was no difference in duration of surgery, SSI, seroma formation or wound disruption between groups.

Conclusions

Suture closure of the subcutaneous fat at CS does not affect long-term cosmetic outcome. (Level I evidence).

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01542346","term_id":"NCT01542346"}}NCT01542346.     

A Randomized Controlled Trial of Innovative Postpartum Care Model for Mother-Baby Dyads

Objective

To evaluate the efficacy, safety, and maternal satisfaction of a newly established integrative postpartum community-based clinic providing comprehensive support for mothers during the first month after discharge from the hospital. Our primary interests were breastfeeding rates, readmission and patient satisfaction.

Methods

A randomized controlled trial was conducted in Ottawa, Canada, where 472 mothers were randomized via a 1:2 ratio to either receive standard of care (n = 157) or to attend the postpartum breastfeeding clinic (n = 315). Outcome data were captured through questionnaires completed by the participants at 2, 4, 12 and 24 weeks postpartum. Unadjusted and adjusted logistic regression models were conducted to determine the effect of the intervention on exclusive breastfeeding at 12 weeks (primary outcome). Secondary outcomes included breastfeeding rate at 2, 4 and 24 weeks, breastfeeding self-efficacy scale, readmission rate, and satisfaction score.

Results

More mothers in the intervention group (n = 195, 66.1%) were exclusively breastfeeding at 12 weeks compared to mothers in the control group (n = 81, 60.5%), however no statistically significant difference was observed (OR = 1.28; 95% CI:0.84–1.95)). The rate of emergency room visits at 2 weeks for the intervention group was 11.4% compared to the standard of care group (15.2%) (OR = 0.69; 95% CI: 0.39–1.23). The intervention group was significantly more satisfied with the overall care they received for breastfeeding compared to the control group (OR = 1.96; 95% CI: 3.50–6.88)).

Conclusion

This new model of care did not significantly increase exclusive breastfeeding at 12 weeks. However, there were clinically meaningful improvements in the rate of postnatal problems and satisfaction that support this new service delivery model for postpartum care. A community-based multidisciplinary postpartum clinic is feasible to implement and can provide appropriate and highly satisfactory care to mother-baby dyads. This model of care may be more beneficial in a population that is not already predisposed to breastfeed.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02043119","term_id":"NCT02043119"}}NCT02043119     

Vector Selection of a Quadripolar Left Ventricular Pacing Lead Affects Acute Hemodynamic Response to Cardiac Resynchronization Therapy: A Randomized Cross-Over Trial

Background

A suboptimal left ventricular (LV) pacing site may account for non-responsiveness of patients to cardiac resynchronization therapy (CRT). The vector selection of a novel quadripolar LV pacing lead, which was mainly developed to overcome technical issues with stimulation thresholds and phrenic nerve capture, may affect hemodynamic response, and was therefore assessed in this study. (German Clinical Trials Register DRKS00000573).

Methods and Results

Hemodynamic effects of a total of 145 LVPCs (9.1 per patient) of CRT devices with a quadripolar LV lead (Quartet™, St. Jude Medical) were assessed in 16/20 consecutive patients by invasive measurement of LV+dP/dt_max at an invasively optimized AV-interval in random order. Optimal (worst) LVPCs per patient were identified as those with maximal (minimal) %change in LV+dP/dt_max (%ΔLV+dP/dt_max) as compared to a preceding baseline. LV+dP/dt_max significantly increased in all 145 LVPCs (p<0.0001 compared to baseline) with significant intraindividual differences between LVPCs (p<0.0001). Overall, CRT acutely augmented %ΔLV+dP/dt_max by 31.3% (95% CI 24%–39%) in the optimal, by 21.3% (95% CI: 15%–27%) in the worst and by 28.2% (95% CI: 21%–36%) in a default distal LVPC. This resulted in an absolute additional acute increase in %ΔLV+dP/dt_max of 10.0% (95% CI: 7%–13%) of the optimal when compared to the worst (p<0.0001), and of 3.1% (95% CI: 1%–5%) of the optimal when compared to the default distal LVPC (p<0.001). Optimal LVPCs were not programmable with a standard bipolar lead in 44% (7/16) of patients.

Conclusion

The pacing configuration of a quadripolar LV lead determinates acute hemodynamic response. Pacing in the individually optimized configuration gives rise to an additional absolute 10% increase in %ΔLV+dP/dt_max when comparing optimal and worst vectors.     

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     

An Adaptive Physical Activity Intervention for Overweight Adults: A Randomized Controlled Trial

Background

Physical activity (PA) interventions typically include components or doses that are static across participants. Adaptive interventions are dynamic; components or doses change in response to short-term variations in participant''s performance. Emerging theory and technologies make adaptive goal setting and feedback interventions feasible.

Objective

To test an adaptive intervention for PA based on Operant and Behavior Economic principles and a percentile-based algorithm. The adaptive intervention was hypothesized to result in greater increases in steps per day than the static intervention.

Methods

Participants (N = 20) were randomized to one of two 6-month treatments: 1) static intervention (SI) or 2) adaptive intervention (AI). Inactive overweight adults (85% women, M = 36.9±9.2 years, 35% non-white) in both groups received a pedometer, email and text message communication, brief health information, and biweekly motivational prompts. The AI group received daily step goals that adjusted up and down based on the percentile-rank algorithm and micro-incentives for goal attainment. This algorithm adjusted goals based on a moving window; an approach that responded to each individual''s performance and ensured goals were always challenging but within participants'' abilities. The SI group received a static 10,000 steps/day goal with incentives linked to uploading the pedometer''s data.

Results

A random-effects repeated-measures model accounted for 180 repeated measures and autocorrelation. After adjusting for covariates, the treatment phase showed greater steps/day relative to the baseline phase (p<.001) and a group by study phase interaction was observed (p = .017). The SI group increased by 1,598 steps/day on average between baseline and treatment while the AI group increased by 2,728 steps/day on average between baseline and treatment; a significant between-group difference of 1,130 steps/day (Cohen''s d = .74).

Conclusions

The adaptive intervention outperformed the static intervention for increasing PA. The adaptive goal and feedback algorithm is a “behavior change technology” that could be incorporated into mHealth technologies and scaled to reach large populations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01793064","term_id":"NCT01793064"}}NCT01793064     

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized,Controlled Trial

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients’ arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718     

A Chinese Mind-Body Exercise Improves Self-Control of Children with Autism: A Randomized Controlled Trial

Self-control problems commonly manifest as temper outbursts and repetitive/rigid/impulsive behaviors, in children with autism spectrum disorders (ASD), which often contributes to learning difficulties and caregiver burden. The present study aims to compare the effect of a traditional Chinese Chan-based mind-body exercise, Nei Yang Gong, with that of the conventional Progressive Muscle Relaxation (PMR) technique in enhancing the self-control of children with ASD. Forty-six age- and IQ-matched ASD children were randomly assigned to receive group training in Nei Yang Gong (experimental group) or PMR (control group) twice per week for four weeks. The participants’ self-control was measured by three neuropsychological tests and parental rating on standardized questionnaires, and the underlying neural mechanism was assessed by the participants’ brain EEG activity during an inhibitory-control task before and after intervention. The results show that the experimental group demonstrated significantly greater improvement in self-control than the control group, which concurs with the parental reports of reduced autistic symptoms and increased control of temper and behaviors. In addition, the experimental group showed enhanced EEG activity in the anterior cingulate cortex, a region that mediates self-control, whereas the PMR group did not. The present findings support the potential application of Chinese Chan-based mind-body exercises as a form of neuropsychological rehabilitation for patients with self-control problems.Chinese Clinical Trial Registry; Registration No.: ChiCTR-TRC-12002561; URL: www.chictr.org.     

Lack of Functional Benefit with Glutamine versus Placebo in Duchenne Muscular Dystrophy: A Randomized Crossover Trial

Background

Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD.

Methodology/Principal Findings

30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.

Conclusions

This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00296621","term_id":"NCT00296621"}}NCT00296621     

Gatifloxacin Versus Ofloxacin for the Treatment of Uncomplicated Enteric Fever in Nepal: An Open-Label,Randomized, Controlled Trial

Background

Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.

Methodology and Principal Findings

Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9–23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98–5.90) in the ofloxacin group versus 3.31 days (IQR 2.29–4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable.

Conclusion

Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. Trial registration: ISRCTN 63006567 (www.controlled-trials.com).     

A Randomized Controlled Trial of Multicomponent Exercise in Older Adults with Mild Cognitive Impairment

Background

To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.

Methodology/Principal Findings

Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).

Conclusions/Significance

The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.

Trial Registration

UMIN-CTR UMIN000003662 ctr.cgi&quest;function&hairsp;&equals;&hairsp;brows&amp;action&hairsp;&equals;&hairsp;brows&amp;type&hairsp;&equals;&hairsp;summary&amp;recptno&hairsp;&equals;&hairsp;R000004436&amp;language&hairsp;&equals;&hairsp;J.     

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     

Improve the Efficiency of Surgery for Femoral Shaft Fractures with A Novel Instrument: A Randomized Controlled Trial

ObjectiveTo improve the efficacy of closed reduction and wire guiding during intramedullary nail internal fixation in femoral shaft fractures.MethodsA novel instrument was designed and manufactured. Sixty-eight patients were enrolled from February 2011 to December 2013. The instrument designed was used during the operation in the experimental group, but not in the control group.ResultsAll patients exhibited fracture union, excluding 1 patient in the experimental group and 2 in the control group who had non-union; all of whom achieved fracture union with reoperation. There were no statistically significant differences in operative blood loss or duration of hospital stay between the groups (P > 0.05). The operative time, frequency of wire drilling, and number of open reduction cases, were significantly smaller in the experimental group than in the control group (P < 0.05).ConclusionFemoral shaft fractures are difficult to reduce using general methods; the novel instrument showed high clinical value and proved effective and safe in assisting with closed reduction and intramedullary nail fixation for femoral shaft fractures.

Trial Registration

ChiCTR ChiCTR-ICR-15007335     

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial

Background

Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%).

Methods and Findings

This randomized controlled trial included children (0.5–10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan–Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7g/dl 7 d or more after admission.The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI −7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI −12, 1; p = 0.24). Delayed parasite clearance was associated with the ^N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms.A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner.

Conclusions

A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children.

Trial registration

Pan African Clinical Trials Registry PACTR201102000277177     

A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese Adults

Background

There is currently no licensed antiviral drug for treatment of dengue. Chloroquine (CQ) inhibits the replication of dengue virus (DENV) in vitro.

Methods and Findings

A double-blind, randomized, placebo-controlled trial of CQ in 307 adults hospitalized for suspected DENV infection was conducted at the Hospital for Tropical Diseases (Ho Chi Minh City, Vietnam) between May 2007 and July 2008. Patients with illness histories of 72 hours or less were randomized to a 3-day course of CQ (n = 153) or placebo (n = 154). Laboratory-confirmation of DENV infection was made in 257 (84%) patients. The primary endpoints were time to resolution of DENV viraemia and time to resolution of DENV NS1 antigenaemia. In patients treated with CQ there was a trend toward a longer duration of DENV viraemia (hazard ratio (HR) = 0.80, 95% CI 0.62–1.05), but we did not find any difference for the time to resolution of NS1 antigenaemia (HR = 1.07, 95% CI 0.76–1.51). Interestingly, CQ was associated with a significant reduction in fever clearance time in the intention-to-treat population (HR = 1.37, 95% CI 1.08–1.74) but not in the per-protocol population. There was also a trend towards a lower incidence of dengue hemorrhagic fever (odds ratio = 0.60, PP 95% CI 0.34–1.04) in patients treated with CQ. Differences in levels of T cell activation or pro- or anti-inflammatory plasma cytokine concentrations between CQ- and placebo-treated patients did not explain the trend towards less dengue hemorrhagic fever in the CQ arm. CQ was associated with significantly more adverse events, primarily vomiting.

Conclusions

CQ does not reduce the durations of viraemia and NS1 antigenaemia in dengue patients. Further trials, with appropriate endpoints, would be required to determine if CQ treatment has any clinical benefit in dengue.

Trial Registration

Current Controlled Trials number ISRCTN38002730.     

Multicomponent Interdisciplinary Group Intervention for Self-Management of Fibromyalgia: A Mixed-Methods Randomized Controlled Trial

BackgroundThis study evaluated the efficacy of the PASSAGE Program, a structured multicomponent interdisciplinary group intervention for the self-management of FMS.MethodsA mixed-methods randomized controlled trial (intervention (INT) vs. waitlist (WL)) was conducted with patients suffering from FMS. Data were collected at baseline (T₀), at the end of the intervention (T₁), and 3 months later (T₂). The primary outcome was change in pain intensity (0-10). Secondary outcomes were fibromyalgia severity, pain interference, sleep quality, pain coping strategies, depression, health-related quality of life, patient global impression of change (PGIC), and perceived pain relief. Qualitative group interviews with a subset of patients were also conducted. Complete data from T₀ to T₂ were available for 43 patients.ResultsThe intervention had a statistically significant impact on the three PGIC measures. At the end of the PASSAGE Program, the percentages of patients who perceived overall improvement in their pain levels, functioning and quality of life were significantly higher in the INT Group (73%, 55%, 77% respectively) than in the WL Group (8%, 12%, 20%). The same differences were observed 3 months post-intervention (Intervention group: 62%, 43%, 38% vs Waitlist Group: 13%, 13%, 9%). The proportion of patients who reported ≥50% pain relief was also significantly higher in the INT Group at the end of the intervention (36% vs 12%) and 3 months post-intervention (33% vs 4%). Results of the qualitative analysis were in line with the quantitative findings regarding the efficacy of the intervention. The improvement, however, was not reflected in the primary outcome and other secondary outcome measures.ConclusionThe PASSAGE Program was effective in helping FMS patients gain a sense of control over their symptoms. We suggest including PGIC in future clinical trials on FMS as they appear to capture important aspects of the patients’ experience.

Trial registration

International Standard Randomized Controlled Trial Number Register ISRCTN14526380     

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

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