Significant Difference In Clinical Efficacy Research Articles

A Randomized Controlled Trial of Atomoxetine in Generalized Social Anxiety Disorder

The current mainstays of social anxiety disorder pharmacotherapy are serotonergic agents, with less known about the efficacy of more noradrenergic drugs. Atomoxetine (ATM), a highly selective norepinephrine reuptake inhibitor, is currently approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). We describe the first controlled trial of ATM with respect to efficacy and tolerability in adults with the generalized subtype of social anxiety disorder (GSAD) without comorbid ADHD. Twenty-seven outpatients with clinically prevailing diagnoses of GSAD by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized in a 1:1 ratio to 10 weeks of double-blind flexible-dose treatment with either ATM 40-100 mg per day (n = 14) or placebo (n = 13). Primary efficacy outcome was score at end point on the Liebowitz Social Anxiety Scale in the intention-to-treat sample. There were no significant group differences in patients completing the study (ATM, 79%; placebo, 77%). Whereas ATM was well tolerated, there were no significant differences in clinical efficacy between ATM and placebo for GSAD. There were few responders overall (ATM, 21%; placebo, 33%), but proportions were similar in each group (chi [1, 26] = 0.47; P = 0.67). Analysis of variance with repeated measures on the Liebowitz Social Anxiety Scale was performed to detect any differential change in social anxiety symptoms between groups. A significant time effect was found (F = 8.71; P = 0.007), but the time-by-treatment interaction was nonsignificant (F = 0.013; P = 0.91). Although the small sample size limits confidence in the reported results, the comparable, and low, response rates for ATM and placebo suggest that in the absence of comorbid ADHD, ATM is unlikely to be an effective agent for the treatment of GSAD.

The Clinical Effectiveness of Retropubic (IVS-02) and Transobturator (IVS-04) Midurethral Slings: Randomized Trial

BackgroundFew series comparing the clinical efficacy of retropubic slings versus transobturator slings for the treatment of female stress urinary incontinence (SUI) are available. ObjectiveTo compare clinical efficacy of retropubic tape operations and transobturator suburethral tape operations for the surgical treatment of female SUI. Design, setting, and participantsFrom January 2003 to December 2005, 611 patients underwent clinical and urodynamic evaluation before surgical treatment for SUI. Patients with advanced urogenital prolapse (pelvic organ prolapse-quantification scale [POP-Q] scale grade >1) were excluded, and 537 patients were included in this study. After 18 mo, 398 women were available for follow-up efficacy evaluation at a tertiary academic center. InterventionAll patients underwent either a retropubic sling procedure or a transobturator sling procedure. Patients were randomly allocated into two study groups at a ratio of 1:1. MeasurementsAfter 18 mo all enrolled patients were clinically checked for clinical efficacy of both procedures. Results and limitationsDemographic and urodynamic parameters of patients were similar in both groups. No bladder injury occurred in the transobturator sling group (IVS-04), whereas 13 intraoperational bladder perforations (6.5%) occurred in the retropubic sling group (IVS-02) (p<0.001). The tape erosion rate was <2.5% in both groups (p=0.7). After 18 mo, 398 patients (201 in the IVS-02 group and 197 in the IVS-04 group) were evaluated in terms of clinical efficacy of the procedures. We found out that there was no statistically significant difference in clinical efficacy between these two procedures (χ2=1.88, p=0.39). In the IVS-02 group, 75.1% of patients (n=151) remained dry (cured), 16.9% of patients (n=34) reported significant improvement, and 8.0% of patients (n=16) were considered as failures. In the IVS-04 group, 74.1% of patients (n=146) remained dry, 14.2% of patients (n=28) reported significant improvement, and 11.7% (n=23) were considered as failures. ConclusionsBased on an 18-mo follow-up, the efficacies of both techniques are comparable; however, the retropubic route appears to be more efficient in the intrinsic sphincter deficiency (ISD) group.

Mahuang Zhisou Capsule in treatment of acute upper respiratory tract infection of external wind-cold syndrome: a multi-center, randomized controlled, and double-blind trial

To evaluate the efficacy and safety of Mahuang Zhisou Capsule (MHZSC), a compound traditional Chinese herbal medicine, in treatment of acute upper respiratory tract infection of wind-cold syndrome. A multi-center, double-blind, double dummy, randomized controlled trial was conducted. A total of 240 patients were randomized into treatment group (120 cases, treated with MHZSC) and control group (120 cases, treated with Mahuang Zhisou Pill). The therapeutic course was 3 days. Seven cases were excluded and three cases lost to follow-up. Two hundred and thirty-three cases entered intention-to-treat (ITT) analysis and 230 cases fitted in per-protocol population set (PPS) analysis. After treatment, the therapeutic effect of upper respiratory tract infection was calculated by ITT and PPS analysis respectively. The significant response rate and total response rate in the treatment group were 78.07% and 98.25% (ITT and PPS), while the significant response rates in the control group were 70.59% (ITT) and 70.69%(PPS), and the total response rates were 95.80% (ITT) and 95.69% (PPS) respectively. There were no significant differences in clinical efficacy between the two groups (P>0.05). MHZSC is effective and safe in treatment of acute upper respiratory tract infection of external wind-cold syndrome.

A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients

BackgroundEmpirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients. MethodsNinety-five patients with febrile neutropenia were included in a prospective, controlled, randomized, non-blind, comparative study. Patients were randomly assigned to one of the treatment groups (63 to the ceftriaxone/ciprofloxacin group and 32 to the ceftazidime/amikacin group) and evaluated as successes or failures according to defined criteria. Daily assessments were made of all patients and all adverse events were recorded. ResultsThe overall incidence of documented infections was 45.9%: 24/47 (51.1%) in the ceftriaxone/ciprofloxacin group and 10/27 (37%) in the ceftazidime/amikacin group. There was a significant difference in clinical efficacy between the groups (p=0.011) at the end of therapy. The ceftriaxone/ciprofloxacin group had an overall incidence of resolution and improvement of 95.7% in comparison to 75% in the ceftazidime/amikacin group. Thirty-nine organisms were isolated, 26 (66.67%) gram-negative and 13 (33.33%) gram-positive. There was a low incidence of adverse events in both groups. ConclusionThe combination of a single, high dose of ceftriaxone plus ciprofloxacin daily was more effective than the standard combination of thrice daily ceftazidime plus amikacin with no significant adverse events in either group.

Anidulafungin: advantage for the newcomer?

Anidulafungin is the most recently approved compound of the echinocandin antifungal class. Its mode of action is the noncompetitive inhibition of β–(1,3)-D-glucan synthesis. Potent fungicidal activity has been demonstrated against many Candida spp., including non-albicansCandida spp. and fluconazole-resistant strains, as well as fungistatic activity against Aspergillus spp. Owing to low oral bioavailability, it can only be administered intravenously. Anidulafungin is not metabolized by the liver and renal clearance is negligible, thus rendering dosage adjustments in patients with impaired hepatic or renal function unnecessary. Due to lack of interference with the cytochrome P450 pathway, it displays minimal drug–drug interaction. Anidulafungin has been approved by the US FDA for the treatment of esophageal and invasive candidiasis after clinical trials demonstrated its noninferiority to fluconazole. In September 2007, anidulafungin gained EMEA approval for the treatment of invasive candidiasis in adult non-neutropenic patients. For those with invasive or noninvasive candidiasis with resistance or intolerance to fluconazole in particular, as well as those requiring antifungal medication, that anidulafungin does not interact with concomitant medication means it may be regarded as a safe and efficacious treatment option. Promising results from animal models and experience with the other echinocandins indicate several potential lines of investigation: invasive aspergillosis, prophylaxis and treatment of transplant patients, and empirical treatment in patients with febrile neutropenia. Significant differences in clinical efficacy or safety favoring anidulafungin over the other echinocandins are yet to be discovered.

Immediate and long-term outcomes of drug-eluting stent implantation for unprotected left main coronary artery disease: Comparison with bare-metal stent implantation

The efficacy and safety of drug-eluting stent (DES) implantation for unprotected left main coronary artery (LMCA) disease remain to be established in different clinical settings. Elective DES implantation for unprotected LMCA stenosis was performed in 220 patients at the Fu Wai Hospital, China, from April 2003 to February 2006. Data derived from the latter group were compared with those derived from 224 patients treated with bare-metal stents (BMSs) before March 2003 in a Chinese registry of unprotected LMCA stenting. Compared with the historical BMS control group, the DES group had more multivessel disease and underwent more bifurcation stenting. The inhospital major adverse cardiac events were significantly higher in the DES than in the BMS recipients (4.1% vs 0.9%, P = .030) because of more complex lesions and procedures in the DES group. During the 15-month mean follow-up period, cumulative cardiac death (0.5% vs 4.9%, P = .004), target-vessel revascularization (5.9% vs 11.6%, P = .034), and major adverse cardiac event (9.5% vs 16.5%, P = .029) rates were significantly lower in the DES than in the BMS group. There was no significant difference in clinical efficacy between sirolimus- and paclitaxel-eluting stents. Angiographic follow-up was performed in 46.4% of DES and 45.7% of BMS recipients, respectively; and the binary restenosis rate was significantly lower in the DES versus the BMS control group (16.7% vs 31.4%, P = .014). Based on this comparison with a historical control, DES implantation for unprotected LMCA appears safe in selected patients and might be more effective in preventing major adverse cardiac events compared with BMS implantation over a mean follow-up period of 15 months.

Addition of Inhaled Tobramycin to Ciprofloxacin for Acute Exacerbations of Pseudomonas aeruginosa Infection in Adult Bronchiectasis

Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.

Practical guidelines for the clinical use of plasma

Despite differences in the composition of fresh frozen plasma (FFP) and solvent/detergent-treated plasma, prospective controlled clinical trials have not revealed any significant difference in clinical efficacy and tolerance between the two types of plasma. Evidence of the clinical efficacy of plasma is mainly based on expert opinion, case reports, and on controlled and uncontrolled observational studies. The application of plasma without laboratory analysis to verify the coagulopathy is normally not justified. With the exception of emergency situations when timely clotting assay results are not available, the administration of plasma in coagulopathy must be verified both clinically and by laboratory analysis before plasma is administered. The rapid infusion of at least 10 ml plasma/kg of body weight is required to increase the respective plasma protein levels significantly. Based on the present state of knowledge, plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding in massive transfusion, disseminated intravascular coagulation, and liver disease. Therapeutic plasma exchange with 40 ml plasma/kg of body weight is the treatment of first choice in acute thrombotic-thrombocytopenic purpura-adult hemolytic uremic syndrome (TTP-HUS). A rare indication is the treatment or prevention of bleeding in congenital factor V or factor XI deficiency, plasma exchange in neonates with severe hemolysis or hyperbilirubinemia, and filling of the oxygenator in extracorporeal membrane oxygenation (ECMO) in neonates. Prothrombin complex concentrates should be preferred to plasma for the reversal of oral anticoagulation in emergency situations, since controlled studies have shown a minor efficacy of plasma. Side effects resulting from the administration of plasma are rare but have to be considered.

Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB–IV non-small cell lung carcinoma: a prospective randomized study

Purpose: To compare a regimen of vinorelbine and cisplatin (VC) to the combination of mitomycin, vindesine, and cisplatin (MVP) in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC). The main endpoits were analysis of objective response rates, toxicity, time to progression, and overall survival. Patients and methods: 247 eligible patients were randomized to receive (a) vinorelbine 25 mg/m 2 intravenous bolus on days 1and 8 plus cisplatin 100 mg/m 2 on day 1 every 4 weeks, or (b) mitomycin c 8 mg/m 2 i.v. on day 1, vindesine 3 mg/m 2 i.v. on days 1, 8, 15 and 22, plus cisplatin 100 mg/m 2 on day 1 every 4 weeks. In subsequent cycles vindesine was given every other week. For both treatments a maximum of six cycles was planned. Patients with performance status 0–2 according to the ECOG scale were enrolled. Response and toxicity were evaluated according to the WHO criteria. Analysis of clinical efficacy was performed according to an intent-to-treat analysis. Results: No statistically significant differences in clinical efficacy were observed between the two chemotherapy regimens. The overall objective response rates were 39% (95% CL, 31–49%) in the VC arm and 42% (95% CL, 33–51%) in the MVP arm ( P=0.13). Median time to progression was 4.2 and 4.5 months for the MVP arm and the VC arm, respectively. Median overall survival was 7 months in the VC arm and 8 months in the MVP one (log–rank test, P=0.898). These differences were not statistically significant. However, leukopenia and thrombocytopenia were significantly higher in the MVP arm than in the VC ( P=0.0001; P=0.0002). Grade 3 alopecia was more frequent in the MVP arm than in the VC one ( P<0.001), which was associated with higher rate of phlebitis ( P=0.037). Conclusion: Data achieved in this study suggest that the vinorelbine–cisplatin doublet is similar to the three-drug MVP regimen in term of overall response rate, time to progressive disease, and overall survival. However, hematological toxicity and alopecia are more frequent and severe in the MVP regimen which therefore appears to be less tolerable than the VC regimen. The combination of vinorelbine and cisplatin may be considered as a reference treatment for future studies on the treatment of advanced NSCLC.

Long-pulsed alexandrite laser-assisted hair removal at 5, 10, and 20 millisecond pulse durations.

Several laser systems with varying wavelengths, pulse durations, and energy fluences are currently utilized for hair removal. However, the ideal laser parameters and treatment candidates for photoepilation remain largely unknown. The medical literature lacks a wealth of experimental data to sufficiently document the long-term safety and efficacy of laser-assisted hair removal. This study examines the clinical efficacy and side effect profile of long-pulsed alexandrite laser-assisted hair removal utilizing laser pulse durations of either 5, 10, or 20 milliseconds (ms). Laser-assisted hair removal was performed on 36 subjects with a long-pulsed alexandrite laser. Areas of unwanted hair growth on the face, back, and legs were divided linearly into four 1 cm2 or 2 cm2 quadrants. Experimental regions included a control quadrant and three additional quadrants, which were treated with the alexandrite laser using an average fluence of 18 J/cm2, with a 10 mm spot size at either a 5, 10, or 20 ms pulse duration. Hair counts and photographs were obtained before treatment, immediately following irradiation, 1 week and 1, 3, and 6 months postoperatively. All laser-treated quadrants displayed a significant delay in hair regrowth compared to control nontreated quadrants at postoperative week 1 and months 1 and 3. Hair counts were reduced by 66% at 1 month, 27% at 3 months, and 4% at 6 months. No significant differences in clinical efficacy or side effect profiles were observed between treatment quadrants, yet a trend towards less post-treatment erythema and hyperpigmentation was noted with the 20 ms pulse duration. Equivalent long-term hair removal for up to 6 months was achieved with the long-pulsed alexandrite laser at 5, 10, and 20 ms pulse durations at an average fluence of 18 J/cm2. Side effects were limited and transient.

Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer.

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.

A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses.

We performed a meta-analysis of randomised clinical studies in which the efficacy and toxicity of the same total daily dose of aminoglycosides administered once-daily was compared with multiple divided daily dosing for treating human infections. Of twenty-eight publications identified from a literature search using Medline 19 publications of 20 study comparisons involving 2881 patients met the criteria for analysis. Netilmicin was investigated in 11 studies, amikacin in seven studies and gentamicin in two studies but no studies of tobramycin met the inclusion criteria. The meta-analysis showed that there was a small, statistically significant difference in clinical efficacy of 3.5% (95% confidence intervals 0.5% to 6.5%, P = 0.027) in favour of once-daily administration but no significant differences in bacteriological efficacy or nephrotoxicity were detected. Auditory and vestibular toxicity rates were low for all agents and no differences in these toxicities were identified between once-daily or multiple-dose administration regimens either clinically or by audiometry or electronystagmography. Aminoglycosides can be given once-daily without loss of efficacy or increased toxicity offering greater simplicity and potentially improved cost-effectiveness than can be achieved by giving these drugs in divided doses.

A large scale, general practice based investigation into the clinical efficacy and tolerability of cefuroxime axetil in women with uncomplicated urinary tract infection

Female patients presenting to their general practitioner with symptoms of uncomplicated urinary tract infection (cystitis) were entered into one of three therapeutic trials in a study programme of cefuroxime axetil (125 mg twice daily or 250 mg twice daily) conducted throughout the United Kingdom. On entry to the study, demographic information, infection recurrence rate and clinical signs and symptoms were recorded and the patient given medication for 7-days' treatment. Post-treatment, clinical signs and symptoms were re-assessed and adverse event data collected. Of the 672 patients who entered the programme, 605 patients completed the course of treatment of whom 510 were taking the 125 mg and 95 taking the 250 mg dosage. No significant difference in clinical efficacy or adverse events was found between the two dosage regimens. Analysis of the changes in symptom severity from the pre-treatment to the post-treatment evaluation for all patients showed a highly significant improvement (p less than 0.001). One hundred and five (15.6%) of the patients who entered the study reported a total of 132 adverse events, 16 of whom were withdrawn from treatment. The most frequent event was diarrhoea/loose motions. This study shows that cefuroxime axetil appears to be effective and well-tolerated for the treatment of cystitis in general practice.

Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Ceftazidime is a new 'third generation' cephalosporin administered intravenously or intramuscularly. Similarly to other third generation cephalosporins it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative aerobic bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains) and is resistant to hydrolysis by most beta-lactamases. Importantly, in vitro ceftazidime is presently the most active cephalosporin available against Pseudomonas aeruginosa, but it is less active against Staphylococcus aureus than first and second generation cephalosporins. Only larger comparative trials are likely to discern any statistically significant differences in clinical efficacy which may exist between ceftazidime and other antibiotics, but ceftazidime appears to be similar in efficacy to 'standard' comparative drugs in lower respiratory tract infections and complicated and/or chronic urinary tract infections among debilitated or hospitalised patients. Thus, in patients having Gram-negative infections at these sites and in whom the potential toxicity of the aminoglycosides is a concern, ceftazidime may be a valuable alternative in that it apparently lacks serious side effects and does not require routine drug plasma concentration monitoring. In fibrocystic patients having acute respiratory tract infections, ceftazidime is highly effective at both reducing symptoms of infection and temporarily reducing the sputum counts of Pseudomonas species. However, in these patients resistance to ceftazidime may develop, as seen with other beta-lactam antibiotics. In the treatment of fever of unknown origin or documented infections in immunocompromised adults and children, ceftazidime appears to be similar in efficacy to various 2- or 3-drug combinations. Nevertheless, the coadministration of an antibiotic having greater efficacy against Gram-positive bacteria should be considered in immunocompromised patients. Results from a small number of comparative trials suggest that ceftazidime may be as effective as the aminoglycosides in intra-abdominal, obstetric and gynaecological, and skin and soft tissue infections. However, further clinical experience, particularly a few well designed comparative studies, is needed to clarify the comparative efficacy in these conditions as well as in septicaemia/bacteraemia, meningitis, and bone and joint infections.

Sustained-Release Theophylline

The serum theophylline concentration profiles and clinical efficacy of two sustained-release theophylline tablets (Quibron-T/SR and Theo-Dur) were compared in 13 asthmatic children requiring continuous theophylline therapy. Quibron-T/SR and Theo-Dur, administered every 12 hours in the same dose for one week, were evaluated in a multiple-dose randomized crossover study. At the end of each week, serial serum theophylline concentrations were measured and spirometry and body plethysmography were performed. No significant differences between treatments were found in bioavailability, adverse effects, clinical symptom scores, or pulmonary function in spite of the fact that Quibron-T/SR and Theo-Dur produced significantly different serum theophylline concentration profiles as measured by a mean percent of fluctuation in serum theophylline levels of 143 for Quibron-T/SR and 65.7 for Theo-Dur. Over the short term of the study the pharmacokinetic differences did not produce significant differences in clinical efficacy.