Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled,randomized, double-blinded,prospective clinical trial

Background  

The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest.     

The effects of KaiXinSan on depression and its association with lipid profiles: A randomized,double-blinded,placebo-controlled trial

BackgroundTraditional Chinese medicine (TCM) KaiXinSan (KXS) has been used to treat depressed patients for a long time, but its potential underlying mechanisms have not been fully understood.HypothesisKXS could mitigate symptoms of patients with atypical depression at least partly via regulating lipid equilibrium.MethodsPatients meeting DSM-IV criteria for mild or moderate depression were assigned into placebo (N = 68) or KXS 3.2 g/day (N = 66) groups in a randomized, double-blinded, placebo-controlled, parallel clinical trial to investigate the anti-depressive efficacy of KXS and its association with serum lipid profile.ResultsThe HAMD score and SDS score at 8 weeks were significantly improved in KXS-treated patients the N-BACK accuracy rate was also increased after 8 weeks of KXS treatment compared with baseline. These results indicated that KXS not only improved the specific symptoms of depression, but also had a beneficial effect on cognitive function related working memory. More importantly, KXS treatment improved patients’ lipid profile by reducing the ratios of LDL/HDL and ApoB/ApoA1 (p < 0.05), as well as ApoC3 level. Moreover, subgroup analysis found that HAMD score was significantly higher in patients with high lipid profile than in those with normal lipid profile, and lipid improvement after 8 weeks of KXS treatment was more obvious in depressed patients with high lipid profile than with normal lipid profile.ConclusionKXS could mitigate symptoms of patients with minor and modest depression at least partly via regulating lipid equilibrium. Its might shed light that KXS may likely contributes to depressed patients with other cardio-metabolic diseases.     

Improvement in multiple dimensions of fatigue in patients with fibromyalgia treated with duloxetine: secondary analysis of a randomized,placebo-controlled trial

Introduction  

Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia.     

No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial

Background

The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients with Alzheimer''s disease (AD).

Methodology/Principal Findings

This double-blind, randomized, placebo-controlled trial was conducted between May 2000 and September 2005 in two hospitals in the Netherlands. 51 patients with mild to moderate AD were enrolled into the study. Patients received 100 mg indomethacin or placebo daily for 12 months. Additionally, all patients received omeprazole. The primary outcome measure was the change from baseline after one year of treatment on the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary outcome measures included the Mini-Mental State Examination, the Clinician''s Interview Based Impression of Change with caregiver input, the noncognitive subscale of the ADAS, the Neuropsychiatric Inventory, and the Interview for Deterioration in Daily life in Dementia. Considerable recruitment problems of participants were encountered, leading to an underpowered study. In the placebo group, 19 out of 25 patients completed the study, and 19 out of 26 patients in the indomethacin group. The deterioration on the ADAS-cog was less in the indomethacin group (7.8±7.6), than in the placebo group (9.3±10.0). This difference (1.5 points; CI −4.5–7.5) was not statistically significant, and neither were any of the secondary outcome measures.

Conclusions/Significance

The results of this study are inconclusive with respect to the hypothesis that indomethacin slows the progression of AD.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00432081","term_id":"NCT00432081"}}NCT00432081     

Influence of atorvastatin on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients: a prospective,randomized, double-masked,placebo-controlled study

Introduction  

Mortality in systemic lupus erythematosus (SLE) patients is influenced by an increased occurrence of severe cardiovascular complications. Statins have been proven to protect a wide spectrum of SLE patients from these complications. This study was conducted to determine the possible efficacy of atorvastatin in SLE patients as assessed by multi-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computed tomography (SPECT) of the myocardium.     

Acute coronary syndrome in patients with prior coronary artery bypass surgery: observations from a 20-year registry in a middle-eastern country

Objectives

Clinical characteristics and trends in the outcome of acute coronary syndrome (ACS) in patients with prior coronary artery bypass graft surgery (CABG) are unclear. The aim of this study was to evaluate clinical characteristics, in-hospital treatment, and outcomes in patients presented with ACS with or without a history of prior CABG over 2 decades.

Methods

Data were derived from hospital-based study for collected data from 1991 through 2010 of patients hospitalized with ACS in Doha, Qatar. Data were analyzed according to their history of prior CABG. Baseline clinical characteristics, in-hospital treatment, and outcome were compared.

Results

A total 16,750 consecutive patients with ACS were studied, of which 693 (4.1%) had prior CABG. Patients with prior CABG were older (mean 60.5±11 vs. 53±12 years; P = 0.001), more likely to be females and have more cardiovascular risk factors than the non-CABG group. Prior CABG patients had larger infarct size, were less likely to receive reperfusion therapy, early invasive therapy and more likely to receive evidence-based therapies when compared to non-CABG patients. In-hospital mortality and stroke rates were comparable between the 2 groups. Over 2 decades, there was reduction in the in-hospital mortality rates and stroke rates in both groups (CABG, death; 13.2% to 4%, stroke; 1.9% to 0.0%, non-CABG, death; 10% to 3.2%, stroke 1.0% to 0.1%; all, p = 0.001).

Conclusion

Significant reduction in-hospital morbidity and mortality among ACS patients with prior CABG over a 20-year period.     

The anti-apoptotic effect of leukotriene B4 in neutrophils: a role for phosphatidylinositol 3-kinase, extracellular signal-regulated kinase and Mcl-1

The constitutive commitment of neutrophils to apoptosis is a key process for the control and resolution of inflammation and it can be delayed by various inflammatory mediators including leukotriene B4 (LTB4). The mechanisms by which LTB4 contributes to neutrophil survival are still unclear and the present work aims at identifying intracellular pathways underlying this effect. Inhibition of human neutrophil apoptosis by LTB4 was abrogated by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin and by the specific MEK inhibitor PD98059. In contrast, inhibitors of p38 MAPK, Jak2/3 and Src did not hinder the anti-apoptotic effect of LTB4. We also investigated the effects of members of the Bcl-2 family as they play a crucial role in the regulation of programmed cell death. When neutrophils were incubated with LTB4 for 1 to 6 h, the mRNA levels of the anti-apoptotic protein Mcl-1 were upregulated approximately 2-fold, while those of the pro-apoptotic protein Bax were downregulated 3- to 4-fold, as determined by real-time PCR. Accordingly, Western blot analysis revealed that the expression of Mcl-1 was upregulated in presence of LTB4, while flow cytometric analysis revealed that Bax protein was downregulated. Furthermore, the modulatory effects of LTB4 on Mcl-1 and Bax proteins were abolished in the presence of either wortmannin or PD98059. Taken together, these results demonstrate the participation of PI3-K and MEK/ERK kinases, as well as regulatory apoptotic proteins such as Mcl-1 and Bax, in the anti-apoptotic effects of LTB4 in human neutrophils.     

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

ABSTRACT: BACKGROUND: Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1--84) as the primary endpoint and (2) 24-hour systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24 hours urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. DISCUSSION: In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607.     

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

Background

The protection afforded by human erythrocyte polymorphisms against the malaria parasite, Plasmodium falciparum, has been proposed to be due to reduced ability of the parasite to invade or develop in erythrocytes. If this were the case, variable levels of parasitaemia and rates of seroconversion to infected-erythrocyte variant surface antigens (VSA) should be seen in different host genotypes.

Methods

To test this hypothesis, P. falciparum parasitaemia and anti-VSA antibody levels were measured in a cohort of 555 asymptomatic children from an area of intense malaria transmission in Papua New Guinea. Linear mixed models were used to investigate the effect of α⁺-thalassaemia, complement receptor-1 and south-east Asian ovalocytosis, as well as glucose-6-phosphate dehydrogenase deficiency and ABO blood group on parasitaemia and age-specific seroconversion to VSA.

Results

No host polymorphism showed a significant association with both parasite prevalence/density and age-specific seroconversion to VSA.

Conclusion

Host erythrocyte polymorphisms commonly found in Papua New Guinea do not effect exposure to blood stage P. falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms.     

No effect of a traditional Chinese medicine, Hochu-ekki-to, on antibody titer after influenza vaccination in man: A randomized, placebo-controlled, double-blind trial

BACKGROUND: It was shown that a traditional Chinese medicine, Hochu-ekki-to (HET), had adjuvant effects in influenza vaccination in an animal experiment. This, however, could not be assessed in a clinical study. METHODS: Thirty-two healthy subjects were randomly assigned to two groups (control and HET groups) in a double-blind manner. HET subjects (n=17) took 7.5 g of HET/day for two weeks; control subjects took the same amount of indistinguishable placebo. Then subjects were vaccinated against influenza (H1N1, H3N2 and B/Shandong). Hemagglutinin titers and natural killer (NK) activity were measured at weeks 0, 1, 2, 4, and 12. RESULTS: Antiinfluenza titers against the three viruses were increased continuously for the first two weeks and leveled off. However, there were no significant differences in any titers between the two groups. NK activity peaked at week 2 without any inter-group differences. CONCLUSION: We could not find any adjuvant effects of HET in this experimental condition.     

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

ABSTRACT: BACKGROUND: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. METHODS: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded. DISCUSSION: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).     

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. METHODS: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. CONCLUSIONS: The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Trial registration Clinicaltrials.gov Identifier NCT01046942.     

Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind,placebo-controlled randomized pilot trial

ObjectiveA double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients.DesignDouble-blind, placebo-controlled randomized trial with blood collection on study entry and day 7.SettingTertiary care children’s hospital.PatientsChildren (0–18 years) with ARDS undergoing mechanical ventilation.Interventions35 children were randomized within 72 h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2 mg/kg loading dose followed by 1 mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7.ResultsAt study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson’s correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity.ConclusionThis pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.     

Smoking cessation initiated during hospital stay for patients with coronary artery disease: a randomized controlled trial

Background

Programs for smoking cessation for cardiac patients are underused in Canada. We examined the efficacy of an intervention for smoking cessation for patients admitted to hospital for coronary artery bypass graft (CABG) or because of acute myocardial infarction (MI).

Methods

Nurses randomly assigned 276 sequential patients admitted because of acute MI or for CABG who met the inclusion criteria. Participants received an intensive or minimal smoking-cessation intervention. The minimal intervention included advice from physicians and nurses and 2 pamphlets. The intensive intervention included the minimal intervention plus 60 minutes of bedside counselling, take-home materials and 7 nurse-initiated counselling calls for 2 months after discharge. The outcomes were point prevalence of abstinence at 3, 6 and 12 months after discharge.

Results

The 12-month self-reported rate of abstinence was 62% among patients in the intensive group and 46% among those in the minimal group (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.2–3.1). Abstinence was confirmed for 54% of patients in the intensive group and 35% in the minimal group (OR 2.0, 95% CI 1.3–3.6). Abstinence was significantly lower among those who used pharmacotherapy than among those who did not (p < 0.001). Continuous 12-month abstinence was 57% in the intensive group and 39% in the minimal group (p < 0.01). It was significantly higher among patients admitted for CABG than among those admitted because of acute MI (p < 0.05).

Interpretation

Providing intensive programs for smoking cessation for patients admitted for CABG or because of acute MI could have a major impact on health and health care costs.Interventions for smoking cessation are underused in cardiac units in Canada,¹ even though coronary artery disease accounts for a large proportion of hospital admissions among adults aged 45 or more years.² Compared with the use of other secondary prevention and management measures (e.g., statins, acetylsalicylic acid, β-blockers and angiotensin-converting-enzyme inhibitors), the use of smoking-cessation measures among those with coronary artery disease results in greater reductions in mortality risk^1,3,4 and greater cost-effectiveness.⁵ Risk reductions in this group include a 32% decrease in nonfatal reinfarction, 36% decrease in mortality,³ 300% reduced risk for repeat coronary artery bypass graft (CABG),⁶ and a decreased risk for restenosis after percutaneous translumial coronary angioplasty from 55% to 38%.⁷In this study, we used an intensive intervention, which is the gold standard for smoking cessation among inpatients. When tested in the United States, this intervention resulted in the highest rates of 1-year confirmed cessation reported in the literature.⁸ The intervention involves 45–60 minutes of bedside education and counselling during hospital stay followed by 7 nurse-initiated telephone counselling sessions after discharge.⁹ US trials have reported 1-year confirmed cessation rates of 61% for this intensive intervention compared to 32% for a brief intervention when tested as a stand-alone program.¹⁰ When tested as part of a rehabilitation program for multiple cardiac risk factors, the cessation rates were 70% and 53%, respectively.¹¹ Despite the success of this approach among cardiac patients, interventions for smoking cessation in inpatients have not been widely adopted in Canada.In this randomized clinical trial, we investigated the efficacy of a minimal intervention and an intensive intervention for smoking cessation among patients admitted to hospital because of acute myocardial infarction or for CABG.     

Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial

For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1) what kinds of commercial interests remain relevant after market approval has been granted, (2) what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3) what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.