抗氧化剂治疗重症急性胰腺炎的临床研究

目的对抗氧化剂治疗重症急性胰腺炎的有效性分析。方法一个随机、安慰剂对照实验,将2002年4月—2006年10月44例患者分成两组,每组22例,抗氧化剂组使用N-乙酰半胱氨酸、硒剂、维生素C静脉滴注,安慰剂组使用安慰剂,治疗7d,在6个观察时间点记录患者的APACHE-Ⅱ评分,Marshall器官功能障碍评分,LODS器官功能障碍评分和血清抗氧化剂水平。结果抗氧化剂组在治疗后3~7d,APACHE-Ⅱ评分明显低于安慰剂组,差异有统计学差异（P〈0.05）,多器官功能障碍发生人数也低于安慰剂组,差异有统计学差异（P〈0.05）,抗氧化剂组病死率为4.5%,安慰剂组病死率高达18%,重症监护时间及住院时间均明显缩短。结论抗氧化剂在治疗重症急性胰腺炎时,能有效减少重症急性胰腺炎及其并发症的发生率和病死率,减轻细胞损害。     

Safety and Efficacy of Vitamin-based Antioxidant Therapy in Patients with Severe Acute Pancreatitis: A Randomized Controlled Trial

Background/Aim:

Oxidative stress plays a major role in the pathogenesis of pancreatitis. Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results. We wished to evaluate the efficacy and safety of antioxidant (vitamin A, vitamin C, vitamin E) therapy in patients with severe acute pancreatitis. Setting and design: This was a single-center, prospective, randomized, open-label with blinded endpoint assessment study of antioxidant therapy, conducted in the emergency department attached to our hospital.

Materials and Methods:

Thirty-nine patients with severe acute pancreatitis were randomly assigned to antioxidant treatment group (n=19) or a control group (n=20) within 96 hours of developing symptoms. Patients in the antioxidant group received antioxidants (vitamin A, vitamin E, vitamin C) in addition to the standard treatment provided to both the groups for a period of 14 days. The primary outcome variable was presence of organ dysfunction at day 7. The secondary outcome variables were length of hospital stay, multiorgan dysfunction (MODS) at day 7, recovery at the end of 4 weeks, complications, and mortality. The change in markers of oxidative stress from baseline was also measured.

Results:

We demonstrated no significant difference in organ dysfunction (P=1.0), MODS (P=0.8), and length of hospital stay (P=0.29) between the two groups. All the patients survived in the antioxidant-treated group, whereas two patients died in the control group. The change in the levels of malondialdehyde, superoxide dismutase, and reduced glutathione were not significantly different in the two groups at day 7. Univariate analysis showed marginal benefit with antioxidant treatment (P=0.034) in patients with severe acute pancreatitis.

Conclusions:

This randomized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis.     

Intravenous n-acetylcysteine, ascorbic acid and selenium-based anti-oxidant therapy in severe acute pancreatitis

BACKGROUND: To observe outcome in a cohort of patients with severe acute pancreatitis receiving multiple anti-oxidant therapy. METHODS: An observational study was carried out in 46 consecutive patients with acute pancreatitis fulfilling current Atlanta consensus criteria for severe disease. All patients received multiple anti-oxidant therapy based on intravenous selenium, N-acetylcysteine and ascorbic acid plus beta-carotene and alpha-tocopherol delivered via nasogastric tube. Principal outcomes were the effect of anti-oxidant supplementation on anti-oxidant levels, morbidity and mortality in patients on anti-oxidant therapy, case-control analysis of observed survival compared to predicted survival derived from logistic organ dysfunction score (LODS), logistic regression analysis of factors influencing outcome and side effect profile of anti-oxidant therapy. RESULTS: Paired baseline and post-supplementation data were available for 25 patients and revealed that anti-oxidant supplementation restored vitamin C (P = 0.003) and selenium (P = 0.028) toward normal. In univariate survival analysis, patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 12.6% for each unit increase (95% CI 6.0% to 19.6%). The mean LODS calculated on admission to hospital was 3.7 (standard error of the mean 4.1) giving a predicted mortality for the cohort of 21%. The observed in-hospital mortality was 43%. CONCLUSIONS: Case-control analyses do not appear to demonstrate any benefit from the multiple anti-oxidant combination of selenium, N-acetylcysteine and ascorbic acid in severe acute pancreatitis.     

Antioxidant therapy for chronic hepatitis C after failure of interferon: Results of phase Ⅱ randomized, double-blind placebo controlled clinical trial

AIM: To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology. RESULTS: Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part Ⅱ of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points. CONCLUSION: Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Antioxidant therapy for chronic hepatitis C after failure of interferon： Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.
METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Intravenous n‐acetylcysteine,ascorbic acid and selenium‐based anti‐oxidant therapy in severe acute pancreatitis

Background: To observe outcome in a cohort of patients with severe acute pancreatitis receiving multiple anti‐oxidant therapy. Methods: An observational study was carried out in 46 consecutive patients with acute pancreatitis fulfilling current Atlanta consensus criteria for severe disease. All patients received multiple anti‐oxidant therapy based on intravenous selenium, N‐acetylcysteine and ascorbic acid plus β‐carotene and α‐tocopherol delivered via nasogastric tube. Principal outcomes were the effect of anti‐oxidant supplementation on anti‐oxidant levels, morbidity and mortality in patients on anti‐oxidant therapy, case‐control analysis of observed survival compared to predicted survival derived from logistic organ dysfunction score (LODS), logistic regression analysis of factors influencing outcome and side effect profile of anti‐oxidant therapy. Results: Paired baseline and post‐supplementation data were available for 25 patients and revealed that anti‐oxidant supplementation restored vitamin C (P?=?0.003) and selenium (P?=?0.028) toward normal. In univariate survival analysis, patient survival to discharge was best predicted by admission APACHE‐II score with relative risk of death increasing 12.6% for each unit increase (95% CI 6.0% to 19.6%). The mean LODS calculated on admission to hospital was 3.7 (standard error of the mean 4.1) giving a predicted mortality for the cohort of 21%. The observed in‐hospital mortality was 43%. Conclusions: Case‐control analyses do not appear to demonstrate any benefit from the multiple anti‐oxidant combination of selenium, N‐acetylcysteine and ascorbic acid in severe acute pancreatitis.     

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial     

Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial.

BACKGROUND & AIMS: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Because ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis, the aim of this study was to assess the efficacy of ulinastatin for the prevention of post-ERCP pancreatitis and hyperenzymemia. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, patients undergoing a first ERCP were randomized to receive ulinastatin (150,000 U) or placebo by intravenous infusion for 10 minutes starting immediately before ERCP. All patients were hospitalized at least 24 hours after ERCP for evaluation of clinical symptoms. Serum pancreatic enzyme levels were measured before and at 4 and 18 hours after ERCP. The primary end point was the incidence of post-ERCP pancreatitis and the secondary objective was the occurrence of hyperenzymemia. RESULTS: A total of 406 patients were enrolled (204 in the ulinastatin group and 202 in the placebo group). There were no differences between the 2 groups regarding baseline characteristics, details of fluoroscopic findings, or endoscopic procedure. The incidence of hyperenzymemia was significantly lower in the ulinastatin group than in the placebo group (amylase, P = .011; lipase, P = .008). Six patients in the ulinastatin group and 15 patients in the placebo group developed pancreatitis (2.9% vs. 7.4%, P = .041). There was no case of severe pancreatitis in either group. Patients who received ulinastatin did not present any side effects related to the medication. CONCLUSIONS: Prophylactic short-term administration of ulinastatin decreases the incidence of pancreatitis and hyperenzymemia after ERCP.     

Cytokine profiles in patients receiving antioxidant therapy within the ANTICIPATE trial

AIM: To measure a broad profile of pro-and anti-inflammatory cytokines in patients with clinically proven chronic pancreatitis (CP) taking either antioxidant therapy or placebo as part of the larger ANTICIPATE study. METHODS: Patients with chronic pancreatitis were recruited to the ANTICIPATE study following informed consent and were randomised to intervention with either antox version 1.2-based antioxidant therapy or placebo. After a separate ethics committee amendment a subgroup of 7 patients from either arm of the study were selected for additional analysis of cytokines. Cytokines were measured at baseline and after 6 mo of either antox therapy or placebo by biochip array and enzyme-linked immunosorbent assay. RESULTS: Antioxidant therapy and placebo groups were well-matched in terms of age, gender, aetiology of CP, opiate use and disease duration. Baseline antioxidant levels were similar in patients allocated to the antioxidant group as compared to the group al- located to placebo. After 6 mo of antioxidant therapythere was significant elevation in vitamin C levels in the intervention group: 17.6 μg/mL (12.8-29.3 μg/mL) compared to 4.8 μg/mL (1.6-9.1 μg/mL) in placebo (P < 0.001; 95%CI: 9.0-20.2) with similar trends in selenium levels. There was no elevation in a broad array of pro-and anti-inflammatory cytokines in the antioxidant group compared to placebo [interleukin (IL)-1B, IL-4, IL-6, IL-10, tumor necrosis factor-α] either at baseline or after 6 mo of antioxidant therapy. CONCLUSION: Cytokine levels were low at baseline and at 6 mo despite a significant elevation in plasma antioxidants. In patients with CP, with opiate-dependent abdominal pain, circulating cytokine levels are low suggesting that pain in this disease is not simply a manifestation of inflammation.     

Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction. BACKGROUND: Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue. METHODS: Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine. RESULTS: Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%). CONCLUSIONS: In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial; http://www.clinicaltrials.gov/ct/show/NCT00186329?order=1; NCT00186329).     

Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis

BACKGROUND: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. FINDINGS: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups. INTERPRETATION: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis     

Antioxidant effects of combined vitamins C and E in acute myocardial infarction. The randomized, double-blind, placebo controlled, multicenter pilot Myocardial Infarction and VITamins (MIVIT) trial

AIMS: There is a large body of evidence that reactive oxygen species (ROS) produced during myocardial ischemia and reperfusion play a crucial role in myocardial damage and endothelial dysfunction. The MIVIT pilot trial was designed to test the effects of antioxidant vitamins C and E on the clinical outcome of patients with AMI. METHODS and RESULTS: In this randomized, double-blind, multicenter trial, 800 patients (mean age 62) with AMI were randomly allocated to receive, on top of routine medication, one of two treatments: vitamin C (1000 mg/12 h infusion) followed by 1200 mg/24 h orally and vitamin E (600 mg/24 h) or matching placebo for 30 days. Primary end point (composite of in-hospital cardiac mortality, non-fatal new myocardial infarction, VT/VF/asystole, shock/pulmonary edema) occurred less frequently in patients treated with antioxidants (55 [14%] vs 75 [19%], OR 0.82 [95% CI, 0.68-1.00], p=0.048). CONCLUSIONS: This randomized pilot trial shows that supplementation with antioxidant vitamins is safe and seems to positively influence the clinical outcome of patients with AMI. A larger study is warranted to provide further evidence of this promising and inexpensive regimen.     

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

BACKGROUND/AIMS: In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K1 in such patients. METHODS: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K(1), or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment. RESULTS: At admission, 13 patients (27%) had either low serum K1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K1, there was one (6%) treatment failure (K1 rise <10 ng/ml above baseline), compared with 12 of the 15 (80%) who received oral K1 (P<0.0001). One patient in the placebo group developed overt vitamin K deficiency. CONCLUSIONS: A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K1. The intestinal absorption of mixed-micellar K1 is unreliable in adults with severe acute liver dysfunction.     

The antioxidant profiles of patients with recurrent acute and chronic pancreatitis

OBJECTIVE: It has been suggested that patients with chronic pancreatitis have antioxidant deficiencies. It is unclear whether these antioxidant deficiencies also occur in patients with recurrent acute pancreatitis and whether this condition represents an intermediate state between normality and chronic pancreatitis. The aim of this study was to determine the antioxidant profiles of patients with pancreatitis (recurrent acute and chronic) and to compare their profiles with a control population. METHODS: The antioxidant profiles of patients with chronic pancreatitis (n = 27) and recurrent acute pancreatitis (n = 11) were determined and compared with the antioxidant profiles of control subjects (n = 19). The following parameters were measured in blood: trace elements (selenium, copper, zinc), vitamins A and E, and carotenoids (alpha-carotene, beta-carotene, xanthine, beta-cryptoxanthine, lycopene). RESULTS: Patients with chronic pancreatitis had significantly lower plasma concentrations of selenium, vitamin A, vitamin E, beta-carotene, xanthine, beta-cryptoxanthine, and lycopene compared with both control subjects and patients with recurrent acute pancreatitis (p < 0.05). There were no significant differences between the antioxidant profiles of patients with chronic pancreatitis due to alcohol excess and patients with idiopathic chronic pancreatitis, or between the antioxidant profiles of patients with recurrent acute pancreatitis and control subjects. CONCLUSIONS: Patients with chronic pancreatitis had evidence of multiple antioxidant deficiencies. The antioxidant profiles of patients with recurrent acute pancreatitis did not differ from those of control subjects, discounting the hypothesis that recurrent acute pancreatitis represents an intermediate state between normality and chronic pancreatitis.     

Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: a randomised controlled trial

BACKGROUND: Previous studies suggested that somatostatin given before endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. However, the routine use of somatostatin in all patients undergoing ERCP is not likely to be cost effective. This study evaluated whether intravenous bolus somatostatin given after diagnostic cholangiopancreatography could reduce the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP procedures. METHODS: In a randomised, double blind, controlled trial, the effect of intravenous bolus somatostatin 250 microg given immediately after diagnostic cholangiopancreatography was compared with that of placebo in patients who required endoscopic sphincterotomy or other therapeutic procedures. The primary end point was the incidence of post-ERCP clinical pancreatitis, and a secondary end point was the incidence of hyperamylasemia. RESULTS: A total of 270 patients were randomised. The somatostatin group (n=135) and the placebo group (n=135) were comparable in age, sex, indications for treatment, and types of procedure. The frequencies of clinical pancreatitis (4.4% v 13.3%; p=0.010) and hyperamylasemia (26.0% v 38.5%; p=0.036) were both significantly lower in the somatostatin group compared with the placebo group. CONCLUSIONS: A single dose of intravenous bolus somatostatin, given immediately after diagnostic cholangiopancreatography, is effective in reducing the incidence of pancreatitis after therapeutic ERCP. This novel approach of administering prophylactic somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.     

Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction

BACKGROUND/AIMS: Exaggerated production of various proteases may account for the late presence of organ dysfunction in acute pancreatitis. This study examined the effects of early administration of gabexate mesilate on the condition of patients with severe acute pancreatitis and organ dysfunctions. METHODOLOGY: Fifty-two patients with acute pancreatitis and organ dysfunction were enrolled. The treatment group included 26 patients receiving intravenous gabexate mesilate infusion at a dose of 100 mg/hr for 7 days. APACHE-II score, clinical and biochemical parameters were monitored intensively. RESULTS: Coagulopathy ileus, and abdominal pain was significantly improved with gabexate mesilate. Gabexate mesilate reduced the necessity for surgical intervention and peritoneal lavage. The 7-day-mortality and 90-day-mortality rates were also significantly reduced with gabexate mesilate therapy. CONCLUSIONS: There are strong indications from this study that early intravenous gabexate mesilate infusion results in improved survival in acute pancreatitis with organ dysfunctions.     

Impact of Vitamin C on Endothelial Function and Exercise Capacity in Patients with a Fontan Circulation

Objective. To evaluate the impact of antioxidant therapy on functional health status in Fontan‐palliated patients. Design. Prospective, randomized, double‐blind, placebo‐controlled trial. Patients. Fifty‐three generally asymptomatic Fontan patients. Interventions. Patients were randomized to receive either high‐dose ascorbic acid (vitamin C) or placebo for 4 weeks. Outcome Measures. Peripheral vascular function, as measured with endothelium‐dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. Results. Twenty‐three vitamin C‐ and 21 placebo‐assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7–18.2) and 11.9 years (IQR 9.0–15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). Conclusions. Short‐term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.     

Intravenous magnesium sulphate provides no additive benefit to standard management in acute asthma

BACKGROUND: Treatment of acute asthma is based on rapid reversal of bronchospasm and airway inflammation. Magnesium sulphate (MgSO(4)) is known to have a bronchodilator effect on smooth muscle but studies have shown conflicting results on its efficacy in acute asthma, although its use is recommended in national and international guidelines. AIMS: To determine if intravenous MgSO(4), when used as an adjunct to standard therapy, improves the outcome in acute asthma. METHODS: A double blind, randomised placebo controlled trial comparing 1.2g MgSO(4) with standard therapy in adult patients with acute asthma. Patients had a PEF 相似文献   

Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study

OBJECTIVE: There is a putative role for antioxidant treatment in osteoarthritis (OA) based on animal, epidemiological, and human clinical studies. Vitamin E, a fat soluble vitamin, is one of the major dietary antioxidants. Short term clinical studies using vitamin E in the form of alpha-tocopherol suggested a benefit over placebo of similar dimension to that of diclofenac for relief of OA pain. METHODS: A six month, double blind, randomised, placebo controlled study of vitamin E 500 IU/day was carried out. Primary outcome measures were pain, stiffness, and function. Statistical analysis was performed on an intention to treat basis. RESULTS: 77 patients were included in the study. Vitamin E showed no benefit over placebo at one month, three months, or six months for any of the outcome measures. The placebo group had higher pain levels (p=0.15) and body mass index (p=0.03) at baseline, and lower pain levels (p=0.02) at completion of the study. Radiological score, exercise score, age, or antioxidant intake at baseline or six months did not differ between the groups. The reasons for the better performance of the placebo group are uncertain but may relate to the initially higher pain score and subsequent regression to the mean. CONCLUSIONS: Vitamin E shows no benefit for the management of symptomatic knee OA. The role of vitamin E in preventing OA progression is currently under investigation.