A randomized, controlled, trial of controlled release paroxetine in fibromyalgia

Purpose

We investigated the efficacy and tolerability of paroxetine controlled release, a selective serotonin reuptake inhibitor in fibromyalgia.

Methods

After excluding patients with current major depression and anxiety disorders, 116 subjects with fibromyalgia were enrolled in a 12-week, randomized, double-blind, placebo-controlled, trial of paroxetine controlled release (12.5-62.5 mg/day). The primary outcome measure was proportion of responders as defined as a ≥ 25% reduction in scores on the Fibromyalgia Impact Questionnaire (FIQ) from randomization to end of treatment. Secondary outcome measures included changes in FIQ scores, Clinical Global Impression -Improvement (CGI-I) and Severity (CGI-S) scores, Visual Analogue Scale for pain scores, number of tender points, and scores on the Sheehan Disability Scale (SDS).

Results

Significantly more patients in paroxetine controlled release group (57%) showed a ≥ 25% reduction in FIQ compared to placebo (33%) (P=.016). Paroxetine controlled release was significantly superior to placebo in reducing the FIQ total score (P =.015). The CGI-I ratings significantly favored the drug over placebo (P<.005). The improvements on other secondary outcome measures between the 2 groups were not statistically significant. Drowsiness, dry mouth, blurred vision, genital disorders, and anxiety were reported more frequently with paroxetine controlled release. The mean dose of paroxetine controlled release was 39.1 mg/day.

Conclusions

Paroxetine controlled release appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia without current mood or anxiety disorders. However, its effect on pain measures seems to be less robust.     

Prospective, controlled, multicentre study of loperamide in pregnancy.

BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies. OBJECTIVES: To determine whether loperamide use in pregnancy is associated with an increased risk of major malformations. The secondary end points were rates of minor malformations, spontaneous and therapeutic abortions, and premature births, and mean birth weights. PATIENTS AND METHODS: Women counselled by five teratogen information centres on the safety and risk of loperamide in pregnancy were followed after delivery and compared with a similar group of women matched for age, smoking, alcohol and other exposures. RESULTS: One hundred and five follow-ups were completed; 89 of the women were exposed to loperamide in the first trimester of pregnancy. There were no statistically significant differences between the study group and the control group in any of the end points that were analyzed. However, of women who took loperamide throughout their pregnancy, 21 of 105 had babies who were 200 g smaller than babies in the control group. CONCLUSIONS: The results of this study suggest that the use of loperamide during pregnancy is not associated with an increased risk of major malformations.     

Gastric preparation for magnetically controlled capsule endoscopy: A prospective,randomized single-blinded controlled trial

Background and aimsMagnetically controlled capsule endoscopy (MCE) is a novel technique for which there is no agreed gastric preparation. We aimed to determine an optimal standardized gastric preparation regimen.Methods120 patients referred for MCE were randomly assigned to gastric preparation with either water alone (A), water with simethicone (B) or water, simethicone and pronase (C). Image quality was assessed using cleanliness and visualization scores, higher scores equating to better image quality.ResultsThe total cleanliness scores were (mean ± SD) 15.83 ± 2.41 (A), 21.35 ± 1.23 (B), and 20.82 ± 1.90 (C). The total visualization scores (mean ± SD) were 10.75 ± 2.02 (A), 15.20 ± 1.32 (B), and 15.08 ± 1.86 (C). While the image quality of the whole stomach in groups B and C were significantly better than group A (P < 0.0001), there was no statistical difference between group B and C (P > 0.05). MCE detected positive findings in 21 (52.5%), 27 (67.5%) and 21 (53.8%) patients in group A, B and C respectively, with no significant difference between groups (P > 0.5).ConclusionsSimethicone swallowed with water prior to MCE produced the optimal gastric mucosal image quality. The addition of pronase had no demonstrable additional benefit.     

A controlled study of clopamide, clorexolone, and hydrochlorothiazide in diabetics

The hyperglycemic effects of clopamide 30 mg/day, clorexolone 25 mg/day and hydrochlorothiazide 25 mg/day were compared in a double-blind trial. The subjects were 18 established diabetics with mild hypertension or diabetic retinopathy. In the 15 patients not receiving insulin, clopamide and clorexolone caused a considerable elevation of the mean blood glucose, but hydrochlorothiazide at the dose used had no significant effect. Clopamide, clorexolone and, to a lesser extent, hydrochlorothiazide lowered the plasma potassium, blood pressure and body weight, and raised the blood urea. In the three insulin-dependent patients the changes in blood glucose were small and not statistically significant, although the changes in most other variables were similar to those described for the remainder of the group. The clinical and metabolic implications of these findings are discussed.     

Double-blind, randomised, controlled trial assessing controller medications in asthma

BACKGROUND: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. METHODS: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.     

Topical treatment of tungiasis: a randomized, controlled trial

Tungiasis is caused by the penetration of the female sand flea Tunga penetrans into the epidermis of its host. Human infestation with this ectoparasite is hyper-endemic in many resource-poor communities in sub-Saharan Africa, the Caribbean and South America and is associated with considerable morbidity. Currently, there is no effective drug available to treat tungiasis (or at least none for which a parasiticidal effect has been clearly demonstrated). In an attempt to fill this gap, the effects of treatment with topical ivermectin (lotion), thiabendazole (ointment and lotion), metrifonate (lotion) or placebo lotion were compared in a randomized trial. A total of 108 subjects with 169 tungiasis-infested feet participated in the study. The results show that topical ivermectin, metrifonate or thiabendazole can each significantly reduce the number of lesions caused by embedded sand fleas. Further studies are needed to optimise the doses and administration of these compounds.     

Randomized,controlled trial of compression gloves in rheumatoid arthritis

A randomized, controlled trial was conducted to determine efficacy of the Isotoner and the Futuro compression gloves in 39 patients with hand syn-ovitis secondary to rheumatoid arthritis. After 7 days of nighttime treatment, both brands of gloves were found to decrease subjective symptoms of pain and stiffness (p < 0.05). In addition, swelling of the proximal interphalangeal joints decreased, while range of motion, rate of finger motion, and grip strength all increased (p < 0.05). Compression gloves should be used with caution in patients with bilateral carpal tunnel syndrome, because 12 of 13 such patients experienced worsening of their symptoms following one nighttime wearing of compression gloves. While both gloves were found to be efficacious in improving the signs and symptoms of hand synovitis, neither glove was found to be superior to the other. Patient preferences related to glove composition and fit may ultimately determine which glove to prescribe.     

Randomized,double-blind,controlled trial of pneumococcal vaccination in renal transplant recipients

Renal transplant recipients are at increased risk for developing invasive pneumococcal disease but may have a poor response to pneumococcal polysaccharide vaccine (PPV23). For them, pneumococcal conjugate vaccine (PCV7) may be more immunogenic. Patients were given a single dose of PPV23 or PCV7 in our randomized, controlled, double-blind trial. Immunogenicity was assessed 8 weeks after vaccination by serotype-specific enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic assay (OPA). Baseline demographics, renal function, time since transplantation, and immunosuppression were comparable. In the PCV7 group, the vaccine response rate was improved for serotypes 23F (P=.046) and 6B (P=.067), and mean fold increases in antibody titer were higher for serotypes 23F (P=.046) and 9V (P=.09). The response rate and mean fold increase in OPA titers were not significantly different between groups. There was a trend toward enhanced immunogenicity for PCV7 by ELISA. However, functional antibody responses were not different.     

Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis

OBJECTIVE: To determine whether long term doxycycline improves symptoms in patients with chronic seronegative or reactive arthritis. METHODS: A randomised, triple blind, controlled clinical trial of three months' treatment with doxycycline or placebo of patients with chronic reactive or seronegative arthritis was conducted. The primary study end points were three month pain and functional status measured by a self administered Arthritis Impact Measurement Scales version 2 (AIMS2) quality of life questionnaire. Secondary end points were pain and functional status at 6-12 months, three month rheumatologist assessed joint count, pain, and arthritis activity, and treatment efficacy in those with previous exposure to chlamydia. RESULTS: Of 60 patients randomly allocated to receive doxycycline or placebo, results from 37 were evaluable at three months. Groups were well balanced for major prognostic variables. Doxycycline had no detectable effect at three months on pain change scores (mean difference 1.5, 95% CI -1.2 to 4.2, p=0.25) or composite functional change scores (mean difference 0.8, 95% CI -5.6 to 7.1, p=0.81). Furthermore, there were no differences in secondary study end points, and no apparent treatment effect in patients with previous chlamydia infection. CONCLUSION: Three months' treatment with doxycycline did not improve pain or functional status in patients with chronic reactive or seronegative arthritis.     

Initial results of multicenter,randomized, controlled therapy studies for ANCA-associated vasculitis

Ohne Zusammenfassung Correspondence to Kirsten de Groot     

Forming giant vesicles with controlled membrane composition, asymmetry, and contents

Growing knowledge of the key molecular components involved in biological processes such as endocytosis, exocytosis, and motility has enabled direct testing of proposed mechanistic models by reconstitution. However, current techniques for building increasingly complex cellular structures and functions from purified components are limited in their ability to create conditions that emulate the physical and biochemical constraints of real cells. Here we present an integrated method for forming giant unilamellar vesicles with simultaneous control over (i) lipid composition and asymmetry, (ii) oriented membrane protein incorporation, and (iii) internal contents. As an application of this method, we constructed a synthetic system in which membrane proteins were delivered to the outside of giant vesicles, mimicking aspects of exocytosis. Using confocal fluorescence microscopy, we visualized small encapsulated vesicles docking and mixing membrane components with the giant vesicle membrane, resulting in exposure of previously encapsulated membrane proteins to the external environment. This method for creating giant vesicles can be used to test models of biological processes that depend on confined volume and complex membrane composition, and it may be useful in constructing functional systems for therapeutic and biomaterials applications.     

国产雷贝拉唑钠治疗十二指肠球部溃疡的多中心随机对照临床研究

雷贝拉唑是新一代质子泵抑制剂（PPI），具有强大、快速抑制胃酸分泌的作用，能快速缓解消化性溃疡（PU）患者的临床症状、促进溃疡愈合。为观察信谊药物研究所研制的雷贝拉唑钠肠溶片治疗十二指肠溃疡（DU）的疗效和安全性，并与日本卫材雷贝拉唑钠肠溶片疗效相比较，协作组在2004年5月至8月间，在上海三家医院对DU治疗进行了临床研究，兹将研究结果报告如下。     

A randomized, controlled trial of interactive, multimedia software for patient colonoscopy education

The purpose of our study was to assess the effectiveness of computer-assisted instruction (CAI) in patients having colonoscopies. We conducted a randomized, controlled trial in large, multispecialty clinic. Eighty-six patients were referred for colonoscopies. The interventions were standard education versus standard education plus CAI, and the outcome measures were anxiety, comprehension, and satisfaction. Computer-assisted instruction had no effect on patients' anxiety. The group receiving CAI demonstrated better overall comprehension (p < 0.001). However, Comprehension of certain aspects of serious complications and appropriate postsedation behavior were unaffected by educational method. Patients in the CAI group were more likely to indicate satisfaction with the amount of information provided when compared with the standard education counterparts (p = 0.001). Overall satisfaction was unaffected by educational method. Computer-assisted instruction for colonoscopy provided better comprehension and greater satisfaction with the adequacy of education than standard education. Computer-assisted instruction helps physicians meet their educational responsibilities with no decrement to the interpersonal aspects of the patient-physician relationship.