The place and significance of comparative trials in German agricultural writings around 1800

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.

Download Full-text

Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-021-02271-5 ◽

2021 ◽

Author(s):

Jon Havelock ◽

Anna-Karina Aaris Henningsen ◽

Bernadette Mannaerts ◽

Joan-Carles Arce ◽

Keyword(s):

Ovarian Stimulation ◽

Implantation Rate ◽

Neonatal Outcomes ◽

Controlled Trials ◽

Efficacy And Safety ◽

Relative Contribution ◽

Follitropin Alfa ◽

Start Up ◽

Comparative Trials

Abstract Purpose To describe the pregnancy and neonatal outcomes using fresh and vitrified/warmed blastocysts obtained from ovarian stimulation with follitropin delta in controlled trials versus follitropin alfa. Methods This investigation evaluated the outcome from 2719 fresh and frozen cycles performed in 1326 IVF/ICSI patients who could start up to three ovarian stimulations in the ESTHER-1 (NCT01956110) and ESTHER-2 (NCT01956123) trials, covering 1012 fresh cycles and 341 frozen cycles with follitropin delta and 1015 fresh cycles and 351 frozen cycles with follitropin alfa. Of the 1326 first cycle patients, 513 continued to cycle 2 and 188 to cycle 3, and 441 patients started frozen cycles after the fresh cycles. Pregnancy follow-up was continued until 4 weeks after birth. Results The overall cumulative take-home baby rate after up to three stimulation cycles was 60.3% with follitropin delta and 60.7% with follitropin alfa (−0.2% [95% CI: −5.4%; 5.0%]), of which the relative contribution was 72.8% from fresh cycles and 27.2% from frozen cycles in each treatment group. Across the fresh cycles, the ongoing implantation rate was 32.1% for follitropin delta and 32.1% for follitropin alfa, while it was 27.6% and 27.8%, respectively, for the frozen cycles. Major congenital anomalies among the live-born neonates up until 4 weeks were reported at an incidence of 1.6% with follitropin delta and 1.8% with follitropin alfa (−0.2% [95% CI: −1.9%; 1.5%]). Conclusions Based on comparative trials, the pregnancy and neonatal outcomes from fresh and frozen cycles provide reassuring data on the efficacy and safety of follitropin delta. Trial registration ClinicalTrials.gov Identifier: NCT01956110 registered on 8 October 2013; NCT01956123 registered on 8 October 2013.

Download Full-text

Less is more when treating the nasal ala with superficial radiotherapy

International Journal of Radiology & Radiation Therapy ◽

10.15406/ijrrt.2020.07.00267 ◽

2020 ◽

Vol 7 (3) ◽

pp. 66-69

Author(s):

Lucy M Butcher ◽

Gerald B Fogarty ◽

Susan Sinclair ◽

Hanna Kuchel ◽

Robert Paver

Keyword(s):

Functional Outcomes ◽

Skin Atrophy ◽

Functional Importance ◽

Less Is More ◽

Skin Cancers ◽

Nasal Ala ◽

Cosmetic Outcomes ◽

Standard Fractionation ◽

Comparative Trials ◽

Common Malignancy

Skin cancer is the most common malignancy, is increasing in incidence, and occurs most commonly on the head and neck. Cancers of the nasal ala pose therapeutic challenges given the cosmetic and functional importance. Both surgery and radiotherapy (RT) have similar oncological outcomes. RT is tissue-conserving and may have an advantage in cosmetic and functional outcomes, but more comparative trials are needed. RT needs to be delivered well to avoid late effects such as skin atrophy, fibrosis and telangiectasia, which may increase with higher dose per fraction. We describe three cases of self-reported thinning of the nasal ala following definitive mildly hypofractionated superficial radiotherapy (SXRT) of 2.5 Gy per fraction. SXRT to skin cancers of the nasal alar with standard fractionation of at most 2 Gy per fraction may be important in ensuring excellent cosmetic outcomes and patient satisfaction.

Download Full-text

Acute migraine therapy: recent evidence from randomized comparative trials

Current Opinion in Internal Medicine ◽

10.1097/mci.0b013e32830c6d6d ◽

2008 ◽

Vol 7 (4) ◽

pp. 372-378

Author(s):

Anna Mett ◽

Peer Tfelt-Hansen

Keyword(s):

Acute Migraine ◽

Migraine Therapy ◽

Comparative Trials

Download Full-text

Statistical Principles for Clinical Trials

Journal of International Medical Research ◽

10.1177/030006059802600201 ◽

1998 ◽

Vol 26 (2) ◽

pp. 57-65 ◽

Cited By ~ 2

Author(s):

R Kay

Keyword(s):

Clinical Trials ◽

Confidence Interval ◽

Sample Size ◽

Sample Size Calculation ◽

P Value ◽

Clinical Value ◽

Treatment Groups ◽

Correct Calculation ◽

Intent To Treat ◽

Comparative Trials

If a trial is to be well designed, and the conclusions drawn from it valid, a thorough understanding of the benefits and pitfalls of basic statistical principles is required. When setting up a trial, appropriate sample-size calculation is vital. If initial calculations are inaccurate, trial results will be unreliable. The principle of intent-to-treat in comparative trials is examined. Randomization as a method of selecting patients to treatment is essential to ensure that the treatment groups are equalized in terms of avoiding biased allocation in the mix of patients within groups. Once trial results are available the correct calculation and interpretation of the P-value is important. Its limitations are examined, and the use of the confidence interval to help draw valid conclusions regarding the clinical value of treatments is explored.

Download Full-text