scholarly journals Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials

2012 ◽  
pp. 9 ◽  
Author(s):  
Amnon Katz ◽  
Lemoine ◽  
Wade ◽  
Nir ◽  
Zisapel
Keyword(s):  
Clinical Trials ◽  
Elderly Patients ◽  
Prolonged Release ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Middle Aged ◽  
Combined Analysis

Anatomy of a trial

PEDIATRICS ◽  
1977 ◽  
Vol 60 (6) ◽  
pp. 932-934
Author(s):  
Neil A. Holtzman
Keyword(s):  
Clinical Trials ◽  
Clinical Situation ◽  
Enzyme Deficiency ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Biochemical Alterations ◽  
New Treatments ◽  
The Way

Efficacy and safety of new treatments can seldom be predicted with certainty. Even when it addresses biochemical alterations, a therapy may not improve the clinical situation. The low-phenylalanine diet for phenylketonuria (PKU), for instance, followed logically from the discovery of an enzyme deficiency, but the diet's effectiveness in preventing retardation in asymptomatic infants was still in doubt a decade after it was introduced. Studies in which some subjects are not treated can often establish the benefits and risks of therapy. Many obstacles, however, lie in the way of controlled clinical trials despite the advantage they offer. The PKU story exemplifies the issues.

Antifungal Prophylaxis in Immunocompromised Hosts

1993 ◽  
Vol 27 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Stan Reents ◽  
S. Diane Goodwin ◽  
Vipul Singh
Keyword(s):  
Clinical Trials ◽  
Antifungal Prophylaxis ◽  
Nausea And Vomiting ◽  
Fungal Colonization ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Immunocompromised Hosts ◽  
The Relationship

OBJECTIVE: To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. DATA EXTRACTION: Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. RESULTS: Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. CONCLUSIONS: Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.

Efficacy and Safety of CHOP-14 in Elderly Patients with Very Poor Risk Diffuse Large B-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3307-3307
Author(s):  
Dorte Tholstrup ◽  
Peter de Nully Brown ◽  
Mads Hansen ◽  
Jesper Jurlander
Keyword(s):  
Clinical Trials ◽  
Cardiac Arrest ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Pneumocystis Carinii ◽  
B Cell Lymphoma ◽  
Efficacy And Safety ◽  
Poor Risk ◽  
Risk Patients

Abstract The outcome of advanced diffuse large cell B-cell lymphoma (DLBCL) has been improved by the “dose-densified” biweekly CHOP-14 regimen. The German NHL-B2 trial has demonstrated favourable efficacy and safety in elderly patients with performance status ≤ 3 and normal organ function. However, a considerable proportion of patients are not eligible for clinical trials due to high age, poor performance, concomitant disease and/or organ dysfunction. The efficacy and safety of CHOP-14 is unknown in this group of very poor risk patients. CHOP-14 was introduced as standard treatment for advanced DLBCL (CSII-IV and/or LDH above UNV and/or bulky tumor ≥ 7.5 cm) at our institution in 2002. Seventy consecutive patients with DLBCL have been treated with 6-8 series CHOP-14 in the period March 2002 to December 2003. Patients with residual disease following chemotherapy were subsequently treated with involved field radiation. In order to estimate the efficacy and safety of CHOP-14 in very poor risk patients, we divided this population into two cohorts; A: standard risk: pts. aged 60–75 years with PS ≤ 3 or pts. aged < 60 years regardless of PS and B: very poor risk: pts. aged 60–75 years with PS = 4 or pts. aged > 75 years regardless of PS. Patient characteristics Age PS ≥ LDH UNV Bulky CS III/IV Extranodal IPI 4–5 B-symptoms; A: 22/44 (50%), B: 15/26 (58%) A (n=44) 60 (26–73) 0 (0–4) 26 (59%) 19 (43%) 25 (57%) 24 (55%) 2 (5%) B (n=26) 76 (64–83) 2 (0–4) 22 (85%) 14 (54%) 21 (81%) 19 (73%) 17 (65%) The response rates in the two cohorts (A vs. B) were CR/Cru: 82% vs. 62% (p=0.06); PR: 2% vs. 8% (p=0.55); NC/PD: 11% vs. 8% (ns). Two year EFS was 66% vs. 37% (p=0.027) and the two year OS was 71% vs. 57% (p=0.04). Concerning toxicity 30/44 (68%) vs. 23/26 (88%) (p=0.08) required hospitalisation for one or more of the following reasons: 50% vs. 65% (p=0.21) due to infection; 9% vs. 15% (p=0.42) due to Pneumocystis Carinii pneumonia; 27% vs. 31% (p=0.75) due to reduced PS mainly caused by malnutrition. The median total number of days in hospital were 8 (1–162) vs. 39 (1–228) days (p=0.002). The therapy-associated deaths without progression were 2/44 (5%) in cohort A (1 cardiac arrest, 1 ileus) compared to 3/26 (12%) in cohort B (1 cardiac arrest, 1 PCP, 1 unknown) (ns). In 3 additional patients in cohort B, treatment was stopped early due to severe infection, resulting in progression and subsequently death. In general dose erosion was minimal, except for vincristin that was reduced due to neuropathy in 20/44 (45%) vs. 10/26 (38%) (p=0.57) of the patients after a median of 5 vs. 4 cycles. The median delay in treatment schedule (schedule erosion) was 8 days (0–95 days) vs. 14 days (0–67 days) (p=0.06). Given the dismal prognosis of the patients in cohort B, the two-year survival rate of 57% is encouraging. However, the increased toxicity with infections and malnutrition, warrants for careful attention to this high risk group of patients, preferably within clinical trials focused on prevention and treatment of infections, improvement of the nutritional status and quality of life.

Adalimumab in the Treatment of Psoriasis: Pooled Efficacy and Safety Results from Three Pivotal Studies

2009 ◽  
Vol 13 (5_suppl) ◽  
pp. S58-S66 ◽  
Author(s):  
Kim Papp ◽  
Martin Okun ◽  
Ronald Vender
Keyword(s):  
Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Severity Index ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Psoriasis Area Severity Index ◽  
Treatment Groups ◽  
Efficacy Measure ◽  
Efficacy Measures ◽  
Necrosis Factor

Background: Adalimumab, a fully human monoclonal antibody, binds to and neutralizes tumor necrosis factor. Objective: To provide an integrated review of efficacy and safety from adalimumab clinical trials in psoriasis. Methods: Pooled analyses were conducted of three placebo-controlled clinical trials of adalimumab (40 mg every other week) in psoriasis patients. The primary efficacy measure was the Psoriasis Area Severity Index (PASI). The Physician's Global Assessment (PGA) was also assessed. Results: At Week 16, mean percentage PASI improvement was 78.3% for adalimumab-treated patients versus 15.1% for placebo-treated patients. A PGA of “Clear” or “Minimal” was achieved in 63.4% of adalimumab-treated patients versus 5.1% of placebo-treated patients. The response to adalimumab was rapid, with significant improvements for adalimumab-treated patients in most efficacy measures by Week 4. Adverse event incidence was similar between treatment groups and consistent with adalimumab safety profiles in other indications. Conclusion: Adalimumab improved psoriasis and was generally safe and well-tolerated.

scholarly journals Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Junzhu Deng ◽  
Haiyang Hu ◽  
Feihong Huang ◽  
Chunlan Huang ◽  
Qianqian Huang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Platelet Response ◽  
Controlled Clinical Trials ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Thrombopoietin Receptor

Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs via indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the Medline, PubMed, Embase, the Cochrane Library, and Web of Science databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 109/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.

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