The effect of salt chamber treatment on bronchial hyperresponsiveness in asthmatics

BACKGROUND: Randomized controlled trials are needed to evaluate the effects of complementary treatments in asthma. This study assessed the effect of salt chamber treatment as an add-on therapy to low to moderate inhaled steroid therapy in asthma patients with bronchial hyperresponsiveness (BHR). METHODS: After a 2-week baseline period, 32 asthma patients who exhibited BHR in the histamine inhalation challenge were randomized: 17 to 2-week active treatment, during which salt was fed to the room by a salt generator, and 15 to placebo. The salt chamber treatment lasted 40 min and was administered five times a week. RESULTS: Median provocative dose causing a decrease of 15% in Fev(1) (PD(15)FEV(1)) [corrected] increased significantly in the active group (P = 0.047) but not in the placebo group. The difference in changes between the active and placebo groups was significant (P = 0.02). Nine patients (56%) in the active group and two patients (17%) in the placebo group exhibited at least one doubling dose decrease in BHR (P = 0.040). Six patients (38%) in the active group and none in the placebo group became non-hyperresponsive (P = 0.017). Neither the peak expiratory flow (PEF) values measured just before and after the treatment, nor FEV(1) values measured before the histamine challenges, changed. The reduction in BHR was not caused by changes in the baseline lung function. CONCLUSIONS: Salt chamber treatment reduced bronchial hyperresponsiveness as an add-on therapy in asthmatics with a low to moderate dose of inhaled steroids. The possibility that salt chamber treatment could serve as a complementary therapy to conventional medication cannot be excluded.     

Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study

To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile.     

Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to 14-year-old children with seasonal allergic rhinitis.

BACKGROUND: Cysteinyl leukotrienes have been found to exert potent inflammatory effects in the upper airways and play a fundamental role in the pathogenesis of allergic rhinitis. Previous studies have reported increased levels of exhaled nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms. OBJECTIVE: To investigate the role of treatment with montelukast on symptoms, eNO levels, and peripheral eosinophil counts of children with seasonal allergic rhinitis during pollen season. METHODS: A randomized, double-blind, parallel-group study performed between April and June 2005 in 57 children aged 7 to 14 years with seasonal allergic rhinitis was performed. The study comprised a 1-week screening period, a 1-week run-in period, and a 2-week treatment period with once daily montelukast, 5 mg, or matching placebo. RESULTS: No significant difference at baseline was found in symptom scores, eNO levels, and blood eosinophil counts between the treatment and placebo groups. After 2 weeks of montelukast treatment, improvements from the baseline in the daytime nasal, composite, and daytime eye symptoms scores were significantly greater in the montelukast group compared with the placebo group (P < .001, P < .001, and P < .01, respectively). A significant decrease was also found in eosinophil counts (P < .001) in the montelukast group compared with the placebo group after treatment. Montelukast treatment did not produce a significant effect on eNO levels compared with placebo (P = .96). CONCLUSION: Montelukast treatment provided significant improvement in symptoms and peripheral eosinophil counts of school-age children with seasonal allergic rhinitis; however, it did not show a significant effect on eNO levels.     

Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial.

BACKGROUND: Hawthorn (Crataegus laevigata) leaves, flowers and berries are used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs. Small-scale human studies support this approach. AIM: To investigate the effects of hawthorn for hypertension in patients with type 2 diabetes taking prescribed drugs. DESIGN OF STUDY: Randomised controlled trial. SETTING: General practices in Reading, UK. METHOD: Patients with type 2 diabetes (n = 79) were randomised to daily 1200 mg hawthorn extract (n = 39) or placebo (n = 40) for 16 weeks. At baseline and outcome a wellbeing questionnaire was completed and blood pressure and fasting blood samples taken. A food frequency questionnaire estimated nutrient intake. RESULTS: Hypotensive drugs were used by 71% of the study population with a mean intake of 4.4 hypoglycaemic and/or hypotensive drugs. Fat intake was lower and sugar intake higher than recommendations, and low micronutrient intake was prevalent. There was a significant group difference in mean diastolic blood pressure reductions (P = 0.035): the hawthorn group showed greater reductions (baseline: 85.6 mmHg, 95% confidence interval [CI] = 83.3 to 87.8; outcome: 83.0 mmHg, 95% CI = 80.5 to 85.7) than the placebo group (baseline: 84.5 mmHg, 95% CI = 82 to 87; outcome: 85.0 mmHg, 95% CI = 82.2 to 87.8). There was no group difference in systolic blood pressure reduction from baseline (3.6 and 0.8 mmHg for hawthorn and placebo groups, respectively; P = 0.329). Although mean fat intake met current recommendations, mean sugar intake was higher and there were indications of potential multiple micronutrient deficiencies. No herb-drug interaction was found and minor health complaints were reduced from baseline in both groups. CONCLUSIONS: This is the first randomised controlled trial to demonstrate a hypotensive effect of hawthorn in patients with diabetes taking medication.     

Budesonide in grass pollen rhinitis.

To determine the relative efficacy, to compare the incidence of adverse experiences, and to assess the systemic glucocorticoid effect of nasal preparations of budesonide, 200 micrograms bid, and placebo, 50 adult patients with seasonal allergic rhinitis due to grass pollen were studied in a stratified, double-blind parallel group design. After a 2-week baseline period, budesonide nasal spray, 100 microgram per nostril twice a day, was compared with placebo nasal spray over a 4-week treatment period. Supplementary treatment with chlorpheniramine, 4-mg tablets, was permitted when necessary to control symptoms. Daily symptom and medication diaries were kept by the patients. Investigator assessments of symptoms and side effects were made at clinic visits at 2-week intervals. At baseline and again towards the end of the study, blood samples were drawn for the determination of plasma cortisol levels and 24-hour urine samples collected for the measurement of 17-hydroxycorticosteroid output. Of the 24 men and 26 women entering, 49 completed the study. Symptom scores for sneezing, stuffy nose, and nasal secretion all decreased dramatically from baseline when budesonide treatment was started. The decrease in symptoms was greater for budesonide than for placebo (P < .001). There was no difference between budesonide and placebo with regard to eye itch and rescue medication used. Morning nasal washes were taken during the grass season before treatment was started and 16 to 17 days after. They showed a significant decrease in TAME esterase levels in secretions in the budesonide treated patients (P = .03) but not in the placebo-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1-h cycle test

We investigated the effect of oral creatine supplementation (20 g d(-1) for 7 days) on metabolism during a 1-h cycling performance trial. Twenty endurance-trained cyclists participated in this double-blind placebo controlled study. Five days after familiarization with the exercise test, the subjects underwent a baseline muscle biopsy. Thereafter, a cannula was inserted into a forearm vein before performing the baseline maximal 1-h cycle (test 1 (T1)). Blood samples were drawn at regular intervals during exercise and recovery. After creatine (Cr) loading, the muscle biopsy, 1-h cycling test (test 2 (T2)) and blood sampling were repeated. Resting muscle total creatine (TCr), measured by high performance liquid chromatography, was increased (P < 0.001) in the creatine group from 123.0 +/- 3.8 - 159.8 +/- 7.9 mmol kg(-1) dry wt, but was unchanged in the placebo group (126.7 +/- 4.7 - 127.5 +/- 3.6 mmol kg(-1) dry wt). The extent of Cr loading was unrelated to baseline Cr levels (r=0.33, not significant). Supplementation did not significantly improve exercise performance (Cr group: 39.1 +/- 0.9 vs. 39.8 +/- 0.8 km and placebo group: 39.3 +/- 0.8 vs. 39.2 +/- 1.1 km) or change plasma lactate concentrations. Plasma concentrations of ammonia (NH(3)) (P < 0.05) and hypoxanthine (Hx) (P < 0.01) were lower in the Cr group from T1 to T2. Our results indicate that Cr supplementation alters the metabolic response during sustained high-intensity submaximal exercise. Plasma data suggest that nett intramuscular adenine nucleotide degradation may be decreased in the presence of enhanced intramuscular TCr concentration even during submaximal exercise.     

Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis

Background: Acute kidney injury (AKI) is among the expected complications of cardiac surgery. Statins with pleiotropic anti-inflammatory and antioxidant effects may be effective in the prevention of AKI. However, the results of studies on the efficacy and safety of statins are varied and require further study. Methods: We conducted a retrospective cohort study to evaluate long-term preoperative intake of atorvastatin and rosuvastatin on the incidence of AKI, based on the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria in the early postoperative period after coronary artery bypass graft surgery (CABG). We performed propensity score matching to compare the findings in our study groups. The incidence of AKI was assessed on day 2 and day 4 after the surgery. Results: The analysis included 958 patients after CABG. After 1:1 individual matching, based on propensity score, the incidence of AKI was comparable both on day 2 after the surgery (7.4%) between the atorvastatin group and rosuvastatin group (6.5%) (OR: 1.182; 95%Cl 0.411–3.397; p = 0.794), and on postoperative day 4 between the atorvastatin group (3.7%) and the rosuvastatin group (4.6%) (OR: 0.723, 95%Cl 0.187–2.792; p = 0.739). Additionally, there were no statistically significant differences in terms of incidence of AKI after 1:1 individual matching, based on propensity score, between the rosuvastatin group and the control group both on postoperative day 2 (OR: 0.692; 95%Cl 0.252–1.899; p = 0.611) and day 4 (OR: 1.245; 95%Cl 0.525–2.953; p = 0.619); as well as between the atorvastatin group and the control group both on postoperative day 2 (OR: 0.549; 95%Cl 0.208–1.453; p = 0.240) and day 4 (OR: 0.580; 95%Cl 0.135–2.501; p = 0.497). Conclusion: Long-term statin use before CABG did not increase the incidence of postoperative AKI. Further, we revealed no difference in the incidence of post-CABG AKI between the atorvastatin and rosuvastatin groups.     

Desloratadine therapy for symptoms associated with perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) has a substantial negative social and economic impact. Recent studies emphasize the potential seriousness of PAR and the need for improved treatment of this condition. OBJECTIVE: To confirm the efficacy and safety of the H1-antihistamine desloratadine in reducing the symptoms of PAR in a randomized, double-blind, placebo-controlled trial. METHODS: Patients with PAR (N = 1,179) from 67 US/international centers received desloratadine, 5 mg once daily, or identical placebo tablets. The primary efficacy measure was the change from baseline to week 4 in average morning and evening reflective total symptom scores (TSSs). Secondary end points included changes from baseline in total nasal and nonnasal symptom scores and peak nasal inspiratory flow (PNIF) rates. RESULTS: Desloratadine was significantly more effective than placebo in reducing morning and evening reflective TSSs for each week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4-week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the desloratadine and placebo groups, respectively (P = .001, desloratadine vs placebo). With desloratadine therapy, significant improvements were also seen in secondary efficacy end points compared with placebo use (total nasal and nonnasal symptom scores: P < or = .04). Improvements in mean morning PNIF were significantly greater in the desloratadine-treated group than in the placebo group (P = .03). CONCLUSIONS: These results confirm and extend previous findings that desloratadine is safe and is associated with a statistically significant reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal airflow, evaluated by PNIF, was statistically significantly improved after desloratadine treatment.     

Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients

BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR). METHODS: After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use. RESULTS: After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group. CONCLUSION: These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.     

Olanzapine versus lithium in the acute treatment of bipolar mania: a double-blind, randomized, controlled trial

BACKGROUND: This multicenter, double-blind, randomized, controlled study conducted in China examined the efficacy and safety of olanzapine versus lithium in the treatment of patients with bipolar manic/mixed episodes. METHODS: Patients with bipolar manic or mixed episode (DSM-IV criteria) and Young Mania Rating Scale (YMRS) score> or =20 at screening received olanzapine (5-20 mg/day, n=69) or lithium carbonate (600-1800 mg/day, n=71) for 4 weeks. The primary outcome was mean change from baseline in Clinical Global Impressions-Bipolar Version Overall Severity of Illness (CGI-BP) score. Secondary efficacy measures included YMRS, Brief Psychiatric Rating Scale (BPRS), and Montgomery-Asberg Depression Rating Scale (MADRS) scores. Safety was also assessed. RESULTS: A significantly greater mean change was observed in olanzapine versus lithium patients in CGI-BP (Overall Severity) (P=0.009), YMRS (P=0.013), BPRS (P=0.032), and CGI-BP (Severity of Mania) (P=0.012) scores. More olanzapine than lithium patients experienced at least one adverse event possibly related to study drug (P=0.038). More olanzapine patients had a clinically significant weight increase (> or =7% of baseline weight) compared to lithium patients (P=0.009). More olanzapine patients completed the study than lithium patients, although this difference was not statistically significant (olz, 91.3%; lith, 78.9%; P=0.057). LIMITATIONS: No placebo arm was included; however both treatments have previously been reported to be more effective than placebo. CONCLUSIONS: These results suggest that olanzapine has superior efficacy to lithium in the acute treatment of patients with bipolar mania over a 4-week period. However, adverse events were experienced by a greater number of olanzapine patients than lithium patients.     

Eosinophil markers in seasonal allergic rhinitis

Background The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon.
Methods Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. ( n =26), 0.2 mg o.d. ( n =25), or placebo (n = 12). Six healthy persons served as controls.
Results During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001 – P<0.05). Significant differences were seen between the steroid grotips and the placebo group for all parameters (P<0.001–F<0.05). Higher eosinophil count (P<0.05), serum EPO (F<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001).
Conclusions Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women

OBJECTIVE: The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women.DESIGN: This was a randomized, double-blind, placebo-controlled trial of menopausal women, aged 38 to 60 years, who experienced 4 to 14 hot flashes per day. After a 1-week run-in period, a total of 190 menopausal women were randomized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks. The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary. The secondary outcomes included changes in quality of life and hormonal profiles.RESULTS: A total of 147 women (77%) completed the study. It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally. At 8 weeks hot flash frequency was reduced by 43% in the 40-mg DRI group and by 41% in the 60-mg DRI group, compared with 32% in the placebo group (P = not significant vs placebo). The corresponding numbers for 12 weeks were 52%, 51%, and 39%, respectively (P = 0.07 and 0.09 vs placebo). When comparing the two treatment groups with the placebo group, there were significant reductions in mean daily hot flash frequency. The supplement (either 40 or 60 mg) reduced hot flash frequency by 43% at 8 weeks (P = 0.1) and 52% at 12 weeks (P = 0.048) but did not cause any significant changes in endogenous sex hormones or thyroid hormones. Menopausal quality of life improved in all three groups, although there were no statistically significant differences between groups.CONCLUSIONS: DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes.     

Effect of isoflavones on lipids and bone turnover markers in menopausal women

OBJECTIVES: The purpose of this analysis was to compare the effects of two dietary supplements derived from red clover to placebo on lipids and bone turnover markers in symptomatic menopausal women. METHODS: The study was a 12-week randomized, double-blind, placebo-controlled trial. Two hundred and fifty-two menopausal women ages 45-60 years experiencing > or =35 hot flashes per week were randomly assigned to Promensil (82 mg total isoflavones), Rimostil (57.2 mg total isoflavones), or placebo. Primary outcome measures were mean absolute changes for HDL-cholesterol, serum osteocalcin, and urinary N-telopeptide. Secondary outcome measures were mean changes of total cholesterol, LDL-cholesterol, the ratio of HDL- to LDL-cholesterol, and triglycerides. RESULTS: Ninety-eight percent of participants completed the 12-week protocol. Women taking Rimostil or Promensil compared to those taking placebo had greater mean increases in HDL-cholesterol; however, this change was small in magnitude (<2 mg/dl) and did not reach significance. There was a significant decrease in triglyceride levels among women taking Rimostil (14.4 mg/dl, P = 0.02) or Promensil (10.9 mg/dl, P = 0.05) compared to those taking placebo. The decrease was primarily among women with elevated baseline triglyceride levels (P for interaction = 0.009). There were no differences in mean changes of total cholesterol, LDL-cholesterol, or the ratio of HDL- to LDL-cholesterol among treatment groups. There were no statistically significant differences among treatment groups for bone turnover markers. CONCLUSIONS: Compared with placebo, both of the supplements containing isoflavones decrease levels of triglycerides in symptomatic menopausal women; however, this effect is small in magnitude.     

A double-blind, randomised, placebo controlled study of venlafaxine XL in patients with generalised anxiety disorder in primary care.

BACKGROUND: Generalised anxiety disorder (GAD) is one of the commonest anxiety disorders and is treated almost entirely in primary care. Most recent studies performed in GAD have excluded depression for regulatory reasons. As GAD is usually a co-morbid disease, often co-existing with depression, the results from recent studies have only limited relevance to the naturalistic population. This study was set up to investigate venlafaxine XL in a more naturalistic population of patients with GAD. AIM: To assess the efficacy of venlafaxine XL in patients with generalised anxiety disorder with and without co-morbid depression. DESIGN OF STUDY: Double-blind, randomised, placebo controlled, parallel-group, 24-week study. SETTING: Primary care in the UK. METHODS: Patients enrolled in the study were over 18 years old, met DSM-IV criteria for GAD, and had a score of 20 or more on the Hamilton Anxiety Scale (HAM-A). A score of more than 23 on the Montgomery Asberg Depression Rating Scale (MADRS) excluded patients. Eligible patients were randomised to receive 75 mg of venlafaxine or a matching placebo. After 2 weeks the dose could be doubled if the physician considered the response to be poor. The study duration was 24 weeks. RESULTS: 244 patients were enrolled, with 122 randomised to the placebo and 122 to venlafaxine. Baseline characteristics were similar for both groups, each having a mean total HAM-A score at baseline of 28. The difference from the placebo group at 24 weeks on the total HAM-A score was 2.1 points (95% 0 to 4.2), which was statistically significant (P = 0.05). Remission rates at week 24 were 27.9% for the venlafaxine XL group and 18.9% for placebo group (P = 0.11). CONCLUSION: Venlafaxine was efficacious in the treatment of patients with GAD with and without depression over a 24-week period.     

Desloratadine improves quality of life and symptom severity in patients with allergic rhinitis

BACKGROUND: Desloratadine is associated with decreased signs and symptoms and improved nasal airflow in multiple clinical trials in patients with allergic rhinitis (AR). The effect of desloratadine on quality of life (QOL) in AR has not been widely reported to date. We compared the effects of desloratadine and placebo on QOL in seasonal AR using validated, disease-specific measures. METHODS: This was a multicenter, double-blind, randomized, parallel-group study of desloratadine 5 mg or placebo daily for 2 weeks in patients with symptomatic seasonal AR. QOL was assessed at baseline and at day 14 using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). AR signs/symptoms and the global response to therapy were measured at baseline and at day 14; signs/symptoms were also rated AM/PM in patient diaries. Adverse events (AE) were recorded. RESULTS: Overall 234 patients received desloratadine and 249 received placebo. At day 14 desloratadine was associated with a significantly larger improvement from baseline in the mean total RQLQ score vs placebo (P = 0.0003). Desloratadine also led to significant improvements from baseline in all RQLQ sub-domains (P < or = 0.043). At day 14 significant decreases from baseline were noted in the desloratadine group for total nasal (P = 0.0003), total non-nasal (P = 0.001) and total symptoms scores (P = 0.0001). Morning AR symptoms were significantly decreased in the desloratadine group after 1 day of treatment. Desloratadine was well tolerated, with an AE rate similar to placebo. CONCLUSION: Significant reductions in signs and symptoms of AR with desloratadine treatment were accompanied by improved disease-specific QOL measures.     

Dose-response comparison of budesonide dry powder inhalers using adenosine monophosphate bronchial challenge.

BACKGROUND: Bronchial hyperresponsiveness to adenosine monophosphate, an indirect measure of airway inflammation, is a sensitive marker of inhaled corticosteroid efficacy. OBJECTIVE: To evaluate the relative therapeutic efficacy of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in patients with mild-to-moderate persistent asthma. METHODS: In a double-masked, dose-response crossover study, 27 patients received inhaled budesonide in cumulative sequential doubling dose increments, 2 weeks per dose, of 200, 400, and 800 microg/d. Each treatment block was preceded by 1- to 3-week placebo run-in and washout periods. End points were measured after each placebo (ie, baseline) and treatment period. Adenosine monophosphate bronchial challenge was the primary outcome, and exhaled nitric oxide, serum eosinophilic cationic protein, spirometry, domiciliary peak expiratory flow, symptoms, and rescue medication use were the secondary outcomes. RESULTS: For the adenosine monophosphate provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20), a significant overall dose-response effect (P = .006) was found, and there was no significant difference between the devices (P = .8). The relative microgram dose potency ratio between Clickhaler and Turbuhaler was 1.11 (95% confidence interval [CI], 0.50-2.46). After administration of the highest dose of budesonide, the mean doubling dilution shift in adenosine monophosphate PC20 from placebo baseline was 3.46 (95% CI, 2.66-4.27) with the Clickhaler vs 3.41 (95% CI, 2.47-4.35) with the Turbuhaler. A significant overall dose-response effect was demonstrated for exhaled nitric oxide (P = .03) but not for any of the other secondary outcome measures. There were no significant differences between the devices for any of the outcome measures. CONCLUSION: Inhaled budesonide exhibited overall dose-response effects on adenosine monophosphate PC20 delivered via Turbuhaler and Clickhaler, with no significant difference between the devices.     

Relationship between Serum Uric Acid Concentration and Acute Kidney Injury after Coronary Artery Bypass Surgery

An elevated serum concentration of uric acid may be associated with an increased risk of acute kidney injury (AKI). The aim of this study was to investigate the impact of preoperative uric acid concentration on the risk of AKI after coronary artery bypass surgery (CABG). Perioperative data were evaluated from patients who underwent CABG. AKI was defined by the AKI Network criteria based on serum creatinine changes within the first 48 hr after CABG. Multivariate logistic regression was utilized to evaluate the association between preoperative uric acid and postoperative AKI. We evaluated changes in C statistic, the net reclassification improvement, and the integrated discrimination improvement to determine whether the addition of preoperative uric acid improved prediction of AKI. Of the 2,185 patients, 787 (36.0%) developed AKI. Preoperative uric acid was significantly associated with postoperative AKI (odds ratio, 1.18; 95% confidence interval, 1.10-1.26; P<0.001). Adding uric acid levels improved the C statistic and had significant impact on risk reclassification and integrated discrimination for AKI. Preoperative uric acid is related to postoperative AKI and improves the predictive ability of AKI. This finding suggests that preoperative measurement of uric acid may help stratify risks for AKI in in patients undergoing CABG.

Graphical Abstract

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Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms

OBJECTIVE: To assess the efficacy and safety of topical micellar nanoparticle estradiol emulsion (MNPEE; Estrasorb; Novavax, Inc., Malvern, PA) in postmenopausal women with moderate to severe vasomotor symptoms. DESIGN: A multicenter, randomized, double-blind, placebo-controlled study was conducted in 200 postmenopausal women with seven or more moderate to severe hot flushes per day. The study consisted of a 3-week screening period followed by a 1-week placebo emulsion run-in period and a 12-week active or placebo treatment period. Women were randomized (1:1) to receive MNPEE (3.45 g daily dose of emulsion containing 8.6 mg estradiol) or matching placebo emulsion. The primary efficacy variable was the change from baseline in the frequency of moderate and severe hot flushes at weeks 4 and 12. Adverse events were monitored throughout the trial. RESULTS: Topical micellar nanoparticle estradiol emulsion was statistically significantly superior to placebo emulsion in reducing the mean frequency of moderate to severe vasomotor symptoms by week 3 (P = 0.003), with superiority to placebo maintained from weeks 4 to 12 (P < 0.001). At week 12 (peak benefit), MNPEE reduced mean daily frequency of hot flush count by 11.1 (P < 0.001 vs placebo). MNPEE significantly reduced mean symptom severity from weeks 4 to 12 (P < 0.001) compared with placebo. At endpoint, mean serum concentrations of estradiol and estrone were 63 and 89 pg/mL, respectively, in the MNPEE group. The mean endpoint ratio of estradiol to estrone in these patients was 0.774. MNPEE was safe and well tolerated. CONCLUSION: Once-daily application of 3.45 g of micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe and effective in providing significant relief of vasomotor symptom frequency and severity in postmenopausal women.     

Comparison of once daily fluticasone propionate aqueous nasal spray with once daily budesonide reservoir powder device in patients with perennial rhinitis

BACKGROUND: Previous studies comparing the corticosteroids fluticasone propionate (FP) and budesonide (BUD) in both perennial and seasonal rhinitis have shown no consistent difference between treatments. However, the therapeutic outcomes may have been influenced by study design. OBJECTIVE: To compare the effect of FP aqueous nasal spray (ANS; 200 microg/day) with BUD reservoir powder device (RPD; 200 microg/day) on rhinitis symptoms, productivity loss and device preference in patients with perennial rhinitis. METHODS: After a 2-week run-in period, 440 patients were randomized to receive either FPANS, BUD RPD or matched placebo (ANS or RPD) for 8 weeks, followed by an open-label 4-week follow-up treatment with FPANS. Patients completed diary card visual analogue scores for nasal symptoms, and questionnaires on satisfaction with the treatment and preferred choice of device. RESULTS: During weeks 1-4, the visual analogue total nasal symptom scores (VATNS) in the FPANS group were significantly lower than scores in the BUD RPD group (mean difference = -17.8; 95% CI = -34.4, -1.3; P = 0.036). FPANS also significantly reduced the VATNS compared with the ANS placebo at all time-points assessed (P < or = 0.005). BUD RPD did not significantly differ from the RPD placebo at weeks 5-8 (P = 0.167), or the ANS placebo at any time-point (P < or = 0.151). Over the 8-week treatment period FPANS was significantly more effective than BUD RPD at reducing sneezing (mean difference = -4.4; 95% CI = -8.6, -0.3; P = 0.036) and nasal itching (mean difference = -5.3; 95% CI = -9.9, -0.8; P = 0.022), and was significantly superior to the ANS placebo for all symptoms assessed at weeks 1-4 and 1-8 (P < 0.016). At the same time-points BUD RPD was no better at alleviating nasal itching than the RPD placebo (P < or = 0.306), and compared with the ANS placebo, significantly reduced only one symptom; nasal blockage (P < or = 0.016). After 8 weeks of treatment, patients preferred the ANS device to the RPD (P < 0.001), and at 12 weeks a significantly greater number of patients were satisfied with FPANS treatment compared with BUD RPD (P = 0.0019) or the respective placebos (P = 0.0001). CONCLUSION: FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo-controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.     

Fexofenadine HCl is safe and effective for treatment of chronic idiopathic urticaria.

BACKGROUND: Fexofenadine is a nonsedating antihistamine approved for treatment of seasonal allergic rhinitis. OBJECTIVE: This dose-finding study assessed the safety and efficacy of fexofenadine in chronic idiopathic urticaria. METHODS: The 4-week, double-blind, randomized, placebo-controlled study included patients diagnosed with chronic urticaria who had moderate to severe pruritus. Patients received twice daily oral doses of placebo or fexofenadine HCl (20, 60, 120, or 240 mg) at 7 AM and 7 PM. Patients recorded scores for pruritus severity and number of wheals (over the previous 12 hours) in a daily diary. Efficacy variables included mean daily changes from baseline in pruritus severity, number of wheals, and interference with sleep and daily activities due to urticaria. RESULTS: Patients (N = 418) from 37 investigative sites were included. All four fexofenadine HCl doses were statistically superior to placebo (P < or = .0115) for reducing pruritus and number of wheals scores over the 4-week treatment period. There were greater reductions in urticaria symptoms in the 60 mg fexofenadine HCl group than in the 20 mg group, while similar reductions were observed in the 60, 120, and 240 mg dose groups. Additionally, patients receiving fexofenadine experienced significantly less interference with sleep and daily activities than patients receiving placebo (P < or = .0014). Adverse events occurred with similar incidence in all treatment groups, with no dose-related increases in any event. CONCLUSIONS: Fexofenadine HCl significantly reduced pruritus severity, number of wheals, and interference with sleep and normal daily activities in patients with chronic urticaria compared with placebo. Twice-daily doses of 60 mg or greater were most effective.