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In patients whose disease did not respond to initial therapy, this was followed by a randomised comparison between non-biological triple DMARD therapy and MTX plus biological (anti-tumour necrosis factor (TNF)) therapy.
These findings are supported by data from other observational studies in patients with type 2 diabetes switching from premix to glargine-based regimen [ 14- 16] and by a randomised comparison of a premix-based regimen versus a glargine-based regimen in type 2 diabetic patients previously treated with a glargine-based regimen plus OADs [ 21].
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Although limited by the lack of a randomised comparison, our results suggest that the promising beneficial effect on surrogate biomarkers observed in phase II trials (Decensi et al, 2007) now has clinical confirmation as a potentially effective risk reduction approach.
START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4+ (cells/mm3) counts >500.
Nevertheless, we recently showed in a randomised comparison of outpatient vaginoscopic hysteroscopy and SIS that the latter still is significantly less discomforting [9].
In a randomised comparison of this type, patient blinding is clearly impossible.
Positive evidence from randomised trials has been lacking, and the British National Lymphoma Investigation therefore commenced a randomised comparison of CHOP vs a third-generation regimen, PACEBOM, in November 1987.
During the trial (from January 2011), a strategy of no antibiotic prescription was added as a randomised comparison, bringing the total number of randomised groups to five (fig 1).
Thus, instead of being a randomised controlled trial it became a randomised comparison of two treatments, both of which were relatively new developments.
The Spanish Lung Cancer Group (Alberola et al, 2001) reported on a randomised comparison of a CDDP-based three-drug combination (CDDP/GEM/VNR) vs non-CDDP sequential doublets (GEM/VNR followed by ifosphamide/VNR) vs CDDP/GEM (reference regimen).
Furthermore, the toxicity for gemcitabine in the CONKO-001 trial appears less than that for 5FU/FA (Neoptolemos et al, 2001, 2004), but a robust assessment of the benefit/risk ratio can only be properly addressed by a concurrently randomised comparison as will be carried out in ESPAC-3.
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