Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial

Aim

Albuminuria is the most important indicator of diabetic nephropathy (DN). Resveratrol, a natural compound found in grape skins and red wine, has antioxidant effects. This study aimed to evaluate the effects of resveratrol on DN.

Terbutaline and diaphragm function in chronic obstructive pulmonary disease: a double-blind randomized clinical trial

We conducted a double-blind, randomized crossover trial to evaluate whether oral terbutaline (2.5 mg orally three times daily for a week) increased the force of diaphragmatic contraction in normocapnic patients with chronic obstructive pulmonary disease. Ten patients with moderate to severe airway obstruction completed the trail. Compared with placebo, terbutaline produced a mean increase of 5.8 cmH2O in peak inspiratory mouth pressure and a mean increase of 5.0 cmH2O in transdiaphragmatic pressure during a maximal inspiratory manoeuvre. These small changes with terbutaline failed to achieve statistical significance. Also, terbutaline failed to alter flow rates (FEV1, Vmax50) or patients' dyspnoea ratings using two separate clinical scales (Pneumoconiosis Research Unit Score and the Modified Dyspnoea Index). Because all observed changes in respiratory muscle strength were small and because the trial had power to detect small changes in inspiratory mouth pressures, we suggest that oral terbutaline at the dose administered in this study has little noteworthy effect on respiratory muscle strength in normocapnic patients with chronic obstructive pulmonary disease.     

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Remote ischemic preconditioning to reduce contrast-induced acute kidney injury in chronic kidney disease: a randomized controlled trial

Background

The impact of contrast-induced acute kidney injury (CI-AKI) on patients with chronic renal disease is well-known. Remote ischemic preconditioning (RIPC) is a non-invasive method that can reduce the risk of CI-AKI, but studies on RIPC have had different results. The aim of the present study was to assess the potential impact of RIPC on CI-AKI.

Methods

In a randomized, double blinded, controlled trial, 132 patients with chronic renal dysfunction (glomerular filtration rate?<?60?mL/min/m²) who underwent coronary angiography or angioplasty received adequate hydration. RIPC was performed in 66 patients by applying an upper arm blood pressure cuff. The cuff was inflated four times for 5?min to 50?mmHg above the systolic blood pressure, followed by deflation for 5?min. In the control group, the blood pressure cuff was inflated only to 10?mmHg below the patient’s diastolic blood pressure. The primary endpoint was an increase in serum cystatin C?≥?10% from baseline to 48–72?h after exposure to the contrast.

Results

The primary endpoint was achieved in 48 (36.4%) patients (24 in each group). RIPC did not show any significant effect on the occurrence of the primary endpoint (P?=?1). In addition, when the results were analyzed based on the Mehran risk score for subgroups of patients, RIPC did not reduce the occurrence of the primary endpoint (P?=?0.97).

Conclusions

In patients at moderate-to-high risk of developing CI-AKI when an adequate hydration protocol is performed, RIPC does not have an additive effect to prevent the occurrence of CI-AKI.

Trial registration

The clinical trial was registered on (Identification number IRCT2016050222935N2, on December 19, 2016 as a retrospective IRCT).

     

Contemplative meditation reduces ambulatory blood pressure and stress-induced hypertension: a randomized pilot trial

A total of 52 pharmacologically untreated subjects with essential hypertension were randomly allocated to either 8 weeks of contemplative meditation combined with breathing techniques (CMBT) or no intervention in this observer-blind controlled pilot trial. CMBT induced clinically relevant and consistent decreases in heart rate, systolic and diastolic blood pressure if measured during office readings, 24-h ambulatory monitoring and mental stress test. Longer-term studies should evaluate CMBT as an antihypertensive strategy.     

Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.

Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.     

Paricalcitol in secondary hyperparathyroidism and the survival benefit in patients with chronic kidney disease

Secondary hyperparathyroidism is a characteristic feature of chronic kidney disease, which develops early in the course of chronic kidney disease, often in a progressive way. It occurs as the renal function continues to decline and is encountered following a series of biochemical abnormalities, which are responsible for initiation and maintenance of increased parathyroid hormone (PTH) secretion. Several agents are used in the management of secondary hyperparathyroidism. Paricalcitol is a new generation selective vitamin D receptor activator that lowers PTH levels by exerting a less hypercalcaemic and hyperphosphataemic effect. In addition, there is emerging evidence of the benefit of paricalcitol in preventing intravascular calcification and proteinuria.     

Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study

Abstract: Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double‐blind, placebo‐controlled study on the effects of melatonin in COPD. Thirty‐six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean ± S.D. = 66.6 ± 7.8 yr) were randomized to receive 3 mg melatonin (N = 18) or placebo for 3 months. Oxidative stress was evaluated by 8‐isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL‐8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8‐isoprostane (T0: mean ± S.E.M. = 20.41 ± 2.92 pg/mL; T1: 18.56 ± 2.68 pg/mL; T2: 12.68 ± 2.04 pg/mL; T3: 12.70 ± 2.18 pg/mL; P = 0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P = 0.03) and 3 months (P = 0.01). Dyspnea was improved by melatonin (P = 0.01), despite no significant changes in lung function or exercise capacity. Placebo‐treated patients, but not those who were given melatonin, showed an increase in IL‐8 (P = 0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long‐term management of these patients.     

Oxymatrine therapy for chronic hepatitis B： A randomized double-blind and placebo-controlled multi-center trial

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.     

Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized,placebo-controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society.We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy. METHODS: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD. Data on clinical efficacy, health-care resource use and productivity loss associated with the management of COPD were prospectively collected. The main outcome measures were the incremental cost-effectiveness of achieving a > or = 10% improvement in FEV1 and of remaining exacerbation-free throughout the study.The economic evaluation was costed from the perspective of the NHS (direct costs) and of society (direct and indirect costs). RESULTS: FP was significantly more effective than placebo in terms of the proportions of patients demonstrating a > or = 10% improvement in FEV1 (32 vs. 19%; P = 0.02) and remaining free of moderate/severe exacerbations (75 vs. 63%; P = 0.02).The difference between the groups in total costs was not significantly different. Incremental cost-effectiveness analyses showed that the additional clinical benefits of FP relativeto placebo, in terms of a > or = 10% improvement in FEV1 or an increased number of patients free of moderate/severe exacerbations, were achieved at minimal additional costs from an NHS perspective (additional 0.25 pounds per day for bath) or at a net saving from a societal perspective. Sensitivity analysis showed that these results were robust to changes in the underlying assumptions. CONCLUSIONS: Treatment with FP was associated with statistically significant clinical benefits in patients with moderate-to-severe COPD currently symptomatic on regular bronchodilator therapy. As the differences in direct and total costs compared with placebo were small and non-significant, this treatment can be considered cost-effective in this patient population.     

Propafenone versus disopyramide: a double-blind randomized crossover trial in patients presenting chronic ventricular arrhythmias

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.

BACKGROUND AND AIMS: Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation. METHODS: This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received tegaserod 2 mg twice daily (n = 450), tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of > or =1 complete spontaneous bowel movement/week vs. baseline during weeks 1-4 (primary variable) and weeks 1-12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits. RESULTS: Responder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group. CONCLUSIONS: Over 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.     

Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.     

Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial

Pulmonary rehabilitation is beneficial for patients with chronic lung disease. However, long-term maintenance has been difficult to achieve after short-term treatment. We evaluated a telephone-based maintenance program after pulmonary rehabilitation in 172 patients with chronic lung disease recruited from pulmonary rehabilitation graduates. Subjects were randomly assigned to a 12-month maintenance intervention with weekly telephone contacts and monthly supervised reinforcement sessions (n = 87) or standard care (n = 85) and followed for 24 months. Except for a slight imbalance between sexes, experimental and control groups were equivalent at baseline and showed similar improvements after rehabilitation. During the 12-month intervention, exercise tolerance (maximum treadmill workload and 6-minute walk distance) and overall health status ratings were better maintained in the experimental group together with a reduction in hospital days. There were no group differences for other measures of pulmonary function, dyspnea, self-efficacy, generic and disease-specific quality of life, and health care use. By 24 months, there were no significant group differences. Patients returned to levels close to but above prerehabilitation measures. We conclude that a maintenance program of weekly telephone calls and monthly supervised sessions produced only modest improvements in the maintenance of benefits after pulmonary rehabilitation.