The Outcomes of a 12-Week Internet Intervention Aimed at Improving Fitness and Health-Related Quality of Life in Overweight Adolescents: The Young & Active Controlled Trial

Background

Overweight and obesity among adolescents may have consequences, with potentially lasting effects on health and health-related quality of life (HRQoL). Excess weight is also associated with decreases in physical activity and cardiorespiratory fitness. The aim of the current study was to investigate the short-term effects of a 12-week Internet intervention in a primary care setting intended to increase cardiorespiratory fitness and HRQoL among overweight and obese adolescents.

Methods

In this controlled trial, participants (13–15 years) were non-randomly allocated to an intervention- or a control group. The intervention group received 12-weeks access to an online program providing tailored physical activity counseling based on principles from Self-determination Theory and Motivational Interviewing. The control group received standard follow-up by the school nurses. The primary outcome measure of cardiorespiratory fitness was determined using a shuttle run test. The secondary outcomes: HRQoL, leisure time exercise, body image and self-determined motivation for physical activity and exercise, were assessed by self-report measures. Age- and gender-adjusted body mass index (BMI) was calculated based on measurements of height and weight. To compare pre-to post intervention differences within groups, a paired samples t-test was used while crude differences between groups were analyzed with an independent samples t-test.

Results

Of the 120 participants, 108 completed the study, 75 in the intervention group and 33 in the control group. Exposure to the intervention had a small effect on cardiorespiratory fitness (0.14; 95% CI [0.01;0.28]; P = 0.04), and a moderate effect on HRQoL (5.22; 95% CI [0.90; 9.53]; P = 0.02). Moreover, the control group increased significantly in BMI, yielding a moderate preventive effect on BMI (−0.39; 95% CI [−0.74;−0.03]; P = 0.03) for the intervention group.

Conclusion

The results suggest that the Internet intervention with tailored physical activity counseling can have beneficial short-term effect on cardiorespiratory fitness, HRQoL and BMI among adolescents with overweight and obesity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01700309","term_id":"NCT01700309"}}NCT01700309     

Effect of High- versus Low-Intensity Supervised Aerobic and Resistance Training on Modifiable Cardiovascular Risk Factors in Type 2 Diabetes; The Italian Diabetes and Exercise Study (IDES)

Background

While current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes.

Objective

To compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors.

Design

Pre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006).

Setting

Twenty-two outpatient diabetes clinics across Italy.

Patients

Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303).

Interventions

Subjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume.

Main Outcome Measure(s)

Hemoglobin (Hb) A_1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores.

Results

Volume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA_1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects.

Conclusions

Data from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors.

Trial Registration

www.ISRCTN.org ISRCTN-04252749.     

Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

Introduction

Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients.

Methods

In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF).

Results

Baseline FIQ fatigue correlated negatively with serum leptin (r = -0.345; P = 0.016) and nerve growth factor (NGF; r = -0.412; P = 0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r = -0.694; P = 0.038). FIQ Fatigue associated negatively with CSF resistin (r = -0.365; P = 0.073). Similarly, FIQ fatigue (r = -0.444; P = 0.026) and MFIGF correlated negatively with CSF adiponectin (r = -0.508; P = 0.01). In lean patients, FIQ fatigue (P = 0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P = 0.017), overweight (MFIGF: P = 0.001), and obese patients (MFIGF: P = 0.016). After 15 weeks, total IGF-1 increased in lean (P = 0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P = 0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r = -0.329; P = 0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r = -0.463; P = 0.034) and positively with ∆neuropeptide Y (NPY) (r = 0.469; P = 0.032). Resistin increased after 30 weeks (P = 0.034). ∆MFIGF correlated negatively with ∆resistin (r = -0.346; P = 0.031), being strongest in obese patients (r = -0.815; P = 0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r = -0.711; P = 0.032).

Conclusions

Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00643006","term_id":"NCT00643006"}}NCT00643006     

Differences in the Acute Effects of Aerobic and Resistance Exercise in Subjects with Type 2 Diabetes: Results from the RAED2 Randomized Trial

Objective

Both aerobic (AER) and resistance (RES) training, if maintained over a period of several months, reduce HbA1c levels in type 2 diabetes subjects. However, it is still unknown whether the short-term effects of these types of exercise on blood glucose are similar. Our objective was to assess whether there may be a difference in acute blood glucose changes after a single bout of AER or RES exercise.

Study Design

Twenty-five patients participating in the RAED2 Study, a RCT comparing AER and RES training in diabetic subjects, were submitted to continuous glucose monitoring during a 60-min exercise session and over the following 47 h. These measurements were performed after 10.9+0.4 weeks of training. Glucose concentration areas under the curve (AUC) during exercise, the subsequent night, and the 24-h period following exercise, as well as the corresponding periods of the non-exercise day, were assessed. Moreover, the low (LBGI) and high (HBGI) blood glucose indices, which summarize the duration and extent of hypoglycaemia or hyperglycaemia, respectively, were measured.

Results

AER and RES training similarly reduced HbA1c. Forty-eight hour glucose AUC was similar in both groups. However, a comparison of glucose AUC during the 60-min exercise period and the corresponding period of the non-exercise day showed that glucose levels were lower during exercise in the AER but not in the RES group (time-by-group interaction p = 0.04). Similar differences were observed in the nocturnal periods (time-by-group interaction p = 0.02). Accordingly, nocturnal LBGI was higher in the exercise day than in the non-exercise day in the AER (p = 0.012) but not in the RES group (p = 0.62).

Conclusions

Although AER and RES training have similar long-term metabolic effects in diabetic subjects, the acute effects of single bouts of these exercise types differ, with a potential increase in late-onset hypoglycaemia risk after AER exercise.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01182948","term_id":"NCT01182948"}}NCT01182948     

Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial

Aims

To assess the determinants of exercise training-induced improvements in glucose control (HbA_1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.

Methods

A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).

Results

Changes in HbA_1C were associated with changes in adiponectin (r = −0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA_1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = −0.26; P<0.03), and PGC-1α (r = −0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA_1C.

Conclusions

Decreases in HbA_1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00458133","term_id":"NCT00458133"}}NCT00458133     

Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis

Introduction

This randomized, controlled study on patients with polymyositis or dermatomyositis was based on three hypotheses: patients display impaired endurance due to reduced aerobic capacity and muscle weakness, endurance training improves their exercise performance by increasing the aerobic capacity, and endurance training has general beneficial effects on their health status.

Methods

In the first part of this study, we compared 23 patients with polymyositis or dermatomyositis with 12 age- and gender-matched healthy controls. A subgroup of patients were randomized to perform a 12-week endurance training program (exercise group, n = 9) or to a non-exercising control group (n = 6). We measured maximal oxygen uptake (VO₂ max) and the associated power output during a progressive cycling test. Endurance was assessed as the cycling time to exhaustion at 65% of VO₂ max. Lactate levels in the vastus lateralis muscle were measured with microdialysis. Mitochondrial function was assessed by measuring citrate synthase (CS) and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities in muscle biopsies. Clinical improvement was assessed according to the International Myositis Assessment and Clinical Studies Group (IMACS) improvement criteria. All assessors were blinded to the type of intervention (that is, training or control).

Results

Exercise performance and aerobic capacity were lower in patients than in healthy controls, whereas lactate levels at exhaustion were similar. Patients in the exercise group increased their cycling time, aerobic capacity and CS and β-HAD activities, whereas lactate levels at exhaustion decreased. Six of nine patients in the exercise group met the IMACS improvement criteria. Patients in the control group did not show any consistent changes during the 12-week study.

Conclusions

Polymyositis and dermatomyositis patients have impaired endurance, which could be improved by 12 weeks of endurance training. The clinical improvement corresponds to increases in aerobic capacity and muscle mitochondrial enzyme activities. The results emphasize the importance of endurance exercise in addition to immunosuppressive treatment of patients with polymyositis or dermatomyositis.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01184625","term_id":"NCT01184625"}}NCT01184625     

Aerobic and Combined Exercise Sessions Reduce Glucose Variability in Type 2 Diabetes: Crossover Randomized Trial

Purpose

To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).

Methods

Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods).

Results

Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session.

Conclusions

Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises.

Trial Registration

Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT00887094","term_id":"NCT00887094"}}NCT00887094.     

DEMO-II Trial. Aerobic Exercise versus Stretching Exercise in Patients with Major Depression—A Randomised Clinical Trial

Background

The effect of referring patients from a clinical setting to a pragmatic exercise intervention for depressive symptoms, cognitive function, and metabolic variables has yet to be determined.

Methods

Outpatients with major depression (DSM-IV) were allocated to supervised aerobic or stretching exercise groups during a three months period. The primary outcome was the Hamilton depression score (HAM-D₁₇). Secondary outcomes were cognitive function, cardiovascular risk markers, and employment related outcomes.

Results

56 participants were allocated to the aerobic exercise intervention versus 59 participants to the stretching exercise group. Post intervention the mean difference between groups was −0.78 points on the HAM-D₁₇ (95% CI −3.2 to 1.6; P = .52). At follow-up, the participants in the aerobic exercise group had higher maximal oxygen uptake (mean difference 4.4 l/kg/min; 95% CI 1.7 to 7.0; P = .001) and visuospatial memory on Rey’s Complex Figure Test (mean difference 3.2 points; 95% CI 0.9 to 5.5; P = .007) and lower blood glucose levels (mean difference 0.2 mmol/l; 95% CI 0.0 to 0.5; P = .04) and waist circumference (mean difference 2.2 cm; 95% CI 0.3 to 4.1; P = .02) compared with the stretching exercise group.

Conclusions

The results of this trial does not support any antidepressant effect of referring patients with major depression to a three months aerobic exercise program. Due to lower recruitment than anticipated, the trial was terminated prior to reaching the pre-defined sample size of 212 participants; therefore the results should be interpreted in that context. However, the DEMO-II trial does suggest that an exercise program for patients with depression offer positive short-term effects on maximal oxygen uptake, visuospatial memory, fasting glucose levels, and waist circumference.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00695552","term_id":"NCT00695552"}}NCT00695552     

Peak Oxygen Uptake after Cardiac Rehabilitation: A Randomized Controlled Trial of a 12-Month Maintenance Program versus Usual Care

Background

Exercise capacity is a strong predictor of survival in patients with coronary artery disease (CAD). Exercise capacity improves after cardiac rehabilitation exercise training, but previous studies have demonstrated a decline in peak oxygen uptake after ending a formal rehabilitation program. There is a lack of knowledge on how long-term exercise adherence can be achieved in CAD patients. We therefore assessed if a 12-month maintenance program following cardiac rehabilitation would lead to increased adherence to exercise and increased exercise capacity compared to usual care.

Materials and Methods

Two-centre, open, parallel randomized controlled trial with 12 months follow-up comparing usual care to a maintenance program. The maintenance program consisted of one monthly supervised high intensity interval training session, a written exercise program and exercise diary, and a maximum exercise test every third month during follow-up. Forty-nine patients (15 women) on optimal medical treatment were included following discharge from cardiac rehabilitation. The primary endpoint was change in peak oxygen uptake at follow-up; secondary endpoints were physical activity level, quality of life and blood markers of cardiovascular risk.

Results

There was no change in peak oxygen uptake from baseline to follow-up in either group (intervention group 27.9 (±4.7) to 28.8 (±5.6) mL·kg (-1) min (−1), control group 32.0 (±6.2) to 32.8 (±5.8) mL·kg (−1) min (−1), with no between-group difference, p = 0.22). Quality of life and blood biomarkers remained essentially unchanged, and both self-reported and measured physical activity levels were similar between groups after 12 months.

Conclusions

A maintenance exercise program for 12 months did not improve adherence to exercise or peak oxygen uptake in CAD patients after discharge from cardiac rehabilitation compared to usual care. This suggests that infrequent supervised high intensity interval training sessions are inadequate to improve peak oxygen uptake in this patient group.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01246570","term_id":"NCT01246570"}}NCT01246570     

The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis – a randomised controlled trial

Background

Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis.

Methods

Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months.

Results

Eighty-five participants (mean FEV₁ 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1–3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1–3]) compared to the control group (2[1–3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047).

Conclusions

Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months.

Trial registry

ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT00885521","term_id":"NCT00885521"}}NCT00885521).     

Blood Pressure Control with a Single-Pill Combination of Indapamide Sustained-Release and Amlodipine in Patients with Hypertension: The EFFICIENT Study

Objective

Despite antihypertensive treatment, most hypertensive patients still have high blood pressure (BP), notably high systolic blood pressure (SBP). The EFFICIENT study examines the efficacy and acceptability of a single-pill combination of sustained-release (SR) indapamide, a thiazide-like diuretic, and amlodipine, a calcium channel blocker (CCB), in the management of hypertension.

Methods

Patients who were previously uncontrolled on CCB monotherapy (BP≥140/90 mm Hg) or were previously untreated with grade 2 or 3 essential hypertension (BP≥160/100 mm Hg) received a single-pill combination tablet containing indapamide SR 1.5 mg and amlodipine 5 mg daily for 45 days, in this multicenter prospective phase 4 study. The primary outcome was mean change in BP from baseline; percentage of patients achieving BP control (BP<140/90 mm Hg) was a secondary endpoint. SBP reduction (ΔSBP) versus diastolic BP reduction (ΔDBP) was evaluated (ΔSBP/ΔDBP) from baseline to day 45. Safety and tolerability were also assessed.

Results

Mean baseline BP of 196 patients (mean age 52.3 years) was 160.2/97.9 mm Hg. After 45 days, mean SBP decreased by 28.5 mm Hg (95% CI, 26.4 to 30.6), while diastolic BP decreased by 15.6 mm Hg (95% CI, 14.5 to 16.7). BP control (<140/90 mm Hg) was achieved in 85% patients. ΔSBP/ΔDBP was 1.82 in the overall population. Few patients (n = 3 [2%]) reported side effects, and most (n = 194 [99%]) adhered to treatment.

Conclusion

In patients who were previously uncontrolled on CCB monotherapy or untreated with grade 2 or 3 hypertension, single-pill combination indapamide SR/amlodipine reduced BP effectively—especially SBP— over 45 days, and was safe and well tolerated.

Trial Registration

Clinical Trial Registry – India CTRI/2010/091/000114     

A Meta-Analysis of Core Stability Exercise versus General Exercise for Chronic Low Back Pain

Objective

To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP).

Summary of Background Data

Exercise therapy appears to be effective at decreasing pain and improving function for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP.

Methods

Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies.

Results

From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain [mean difference (−1.29); 95% confidence interval (−2.47, −0.11); P = 0.003] and disability [mean difference (−7.14); 95% confidence interval (−11.64, −2.65); P = 0.002] at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months [mean difference (−0.50); 95% confidence interval (−1.36, 0.36); P = 0.26] and 12 months [mean difference (−0.32); 95% confidence interval (−0.87, 0.23); P = 0.25].

Conclusions

Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.     

Acute Effects of Aerosolized Iloprost in COPD Related Pulmonary Hypertension - A Randomized Controlled Crossover Trial

Background

Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).

Objectives

To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.

Methods

A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.

Results

Both iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means −1.0%, p = 0.035) as well as high dose iloprost (−2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (−76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (−3.0l/min, p<0.001).

Conclusions

Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.

Trial Registration

Controlled-Trials.com ISRCTN61661881     

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.     

Feasibility of a Combined Aerobic and Strength Training Program and Its Effects on Cognitive and Physical Function in Institutionalized Dementia Patients. A Pilot Study

Objectives

We examined the feasibility of a combined aerobic and strength training program in institutionalized dementia patients and studied the effects on cognitive and physical function.

Methods

Thirty-three patients with dementia, recruited from one nursing home, participated in this non-randomized pilot study (25 women; age = 85.2±4.9 years; Mini Mental State Examination = 16.8±4.0). In phase 1 of the study, seventeen patients in the Exercise group (EG) received a combined aerobic and strength training program for six weeks, five times per week, 30 minutes per session, in an individually supervised format and successfully concluded the pre and posttests. In phase 2 of the study, sixteen patients in the Social group (SG) received social visits at the same frequency, duration, and format and successfully concluded the pre and posttests.

Results

Indices of feasibility showed that the recruitment and adherence rate, respectively were 46.2% and 86.3%. All EG patients completed the exercise program according to protocol without adverse events. After the six-week program, no significant differences on cognitive function tests were found between the EG and SG. There was a moderate effect size in favor for the EG for the Visual Memory Span Forward; a visual attention test. There were significant differences between groups in favor for the EG with moderate to large effects for the physical tests Walking Speed (p = .003), Six-Minute Walk Test (p = .031), and isometric quadriceps strength (p = .012).

Conclusions

The present pilot study showed that it is feasible to conduct a combined aerobic and strength training program in institutionalized patients with dementia. The selective cognitive visual attention improvements and more robust changes in motor function in favor of EG vs. SG could serve as a basis for large randomized clinical trials.

Trial Registration

trialregister.nl 1230     

Oral Doxycycline Reduces Pterygium Lesions; Results from a Double Blind,Randomized, Placebo Controlled Clinical Trial

Purpose

To determine whether oral doxycycline treatment reduces pterygium lesions.

Design

Double blind, randomized, placebo controlled clinical trial.

Participants

98 adult patients with primary pterygium.

Methods

Patients were randomly assigned to receive 100 mg oral doxycycline twice a day (49 subjects), or placebo (49 subjects), for 30 days. Photographs of the lesion were taken at the time of recruitment and at the end of the treatment. Follow-up sessions were performed 6 and 12 months post-treatment. Statistical analyses for both continuous and categorical variables were applied. p values of less than 0.05 were considered to indicate statistical significance.

Main Outcome Measures

The primary endpoint was the change in lesion size after 30 days of treatment.

Results

The primary endpoint was not met for the whole population but subgroup analysis showed that doxycycline was effective in patients of Caucasian origin while other ethnicities, mostly Hispanic, did not respond to the treatment. Moreover, there was a correlation between age and better response (p = 0.003). Adverse events were uncommon, mild, and in agreement with previous reports on short doxycycline treatments.

Conclusions

Oral doxycycline was superior to placebo for the treatment of primary pterygia in older Caucasian patients. These findings support the use of doxycycline for pterygium treatment in particular populations.

Trial Registration

European Union Clinical Trials Register EudraCT 2008-007178-39     

Serological identification of fast progressors of structural damage with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruction. We investigated whether baseline serum C1M levels could identify structural progressors and if the biomarker levels changed during anti-inflammatory treatment with tocilizumab (TCZ).

Methods

The LITHE-biomarker study ({"type":"clinical-trial","attrs":{"text":"NCT00106535","term_id":"NCT00106535"}}NCT00106535, n = 585) was a one-year phase III, double-blind, placebo (PBO)-controlled, parallel group study of TCZ 4 or 8 mg/kg every four weeks, in RA patients on stable doses of methotrexate (MTX). Spearman''s ranked correlation was used to assess the correlation between baseline C1M levels and structural progression at baseline and at weeks 24 and 52. Multivariate regression was performed for delta structural progression. Change in C1M levels were studied as a function of time and treatment.

Results

At baseline, C1M was significantly correlated to C-reactive protein (P <0.0001), visual analog scale pain (P <0.0001), disease activity score28-erythrocyte sedimentation rate (DAS28-ESR) (P <0.0001), joint space narrowing (JSN) (P = 0.0056) and modified total Sharp score (mTSS) (P = 0.0006). Baseline C1M was significantly correlated with delta-JSN at Week 24 (R² = 0.09, P = 0.0001) and at Week 52 (R² = 0.27, P <0.0001), and with delta-mTSS at 24 weeks (R² = 0.006, P = 0.0015) and strongly at 52 weeks (R² = 0.013, P <0.0001) in the PBO group. C1M levels were dose-dependently reduced in the TCZ + MTX group.

Conclusions

Baseline C1M levels correlated with worsening joint structure over one year. Serum C1M levels may enable identification of those RA patients that are in most need of aggressive treatment

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00106535","term_id":"NCT00106535"}}NCT00106535     

Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

Study Objectives

To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.

Design

Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.

Setting

Community setting: residential sleep/performance testing facility.

Participants

Fifty-one older adults with insomnia (aged 65–85).

Interventions

Eight weeks of computerized cognitive training for older adults with insomnia.

Results

Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.

Conclusions

New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00901641","term_id":"NCT00901641"}}NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641     

The Relationship between the Blood Pressure Responses to Exercise following Training and Detraining Periods

Background

Exercise training lowers blood pressure (BP), while BP increases and returns to pre-training values with detraining. Yet, there is considerable variability in these BP responses. We examined the relationship between the BP responses after 6 months of training followed by 2 weeks of detraining among the same people.

Methodology/Principal Findings

Subjects (n = 75) (X+SD, 50.2±10.6 yr) were sedentary, obese, and had prehypertension. They completed an aerobic (n = 34); resistance (n = 28); or aerobic + resistance or concurrent (n = 13) exercise training program. We calculated a metabolic syndrome z score (MetSz). Subjects were classified as BP responders (BP decreased) or non-responders (BP increased) to training and detraining. Linear and multivariable regression tested the BP response. Chi Square tested the frequency of responders and non-responders. The systolic BP (SBP, r = −0.474) and diastolic (DBP, r = −0.540) response to training negatively correlated with detraining (p<0.01), independent of modality (p>0.05). Exercise responders reduced SBP 11.5±7.8 (n = 29) and DBP 9.8±6.2 mmHg (n = 31); non-responders increased SBP 7.9.±10.9 (n = 46) and DBP 4.9±7.1 mmHg (n = 44) (p<0.001). We found 65.5% of SBP training responders were SBP detraining non-responders; while 60.9% of SBP training non-responders were SBP detraining responders (p = 0.034). Similarly, 80.6% of DBP training responders were DBP detraining non-responders; while 59.1% of DBP training non-responders were DBP detraining responders (p<0.001). The SBP detraining response (r = −0.521), resting SBP (r = −0.444), and MetSz (r = 0.288) explained 44.8% of the SBP training response (p<0.001). The DBP detraining response (r = −0.553), resting DBP (r = −0.450), and MetSz (r = 0.463) explained 60.1% of the DBP training response (p<0.001).

Conclusions/Significance

As expected most subjects that decreased BP after exercise training, increased BP after detraining. An unanticipated finding was most subjects that increased BP after exercise training, decreased BP after detraining. Reasons why the negative effects of exercise training on BP maybe reversed with detraining among some people should be explored further.

Trial Registration Information

ClinicalTrials.gov 1R01HL57354; 2003–2008; {"type":"clinical-trial","attrs":{"text":"NCT00275145","term_id":"NCT00275145"}}NCT00275145