of gastric injury similar to that of a placebo, and for meloxicam 15 mg per day a level of injury lower than that of other NSAIDs; however, in clinical practice meloxicam can still cause some ulcer complications. Valdecoxib and rofecoxib were about 300 times more potent at inhibiting COX-2 than COX-1, but too toxic for the heart, suggesting the possibility of relief from pain and inflammation without gastrointestinal irritation, and promising to be a boon for those who had previously experienced adverse effects or had comorbidities that could lead to such complications. Celecoxib is approximately 30 times more potent at inhibiting COX-2 than COX-1, with etoricoxib being 106 times more potent. Research fraud Between 1996 and 2009, Scott Reuben purportedly conducted clinical research on the use of COX-2 inhibitors, often in combination with gabapentin or pregabalin, for the prevention and treatment of post-surgical pain, research which was found in 2009 to have been faked. Reuben pleaded guilty, paid fines and served six months in jail, and lost his medical license. A 2009 review of meta-articles used in evidence-based medicine found that while some reviews were no longer valid when the Reuben studies were removed, the conclusions in the majority of them remained unchanged. The review found that the key Reuben claims that needed to be re-examined were "the absence of detrimental effects of coxibs on bone healing after spine surgery, the beneficial long-term outcome after preemptive administration of coxibs including an allegedly decreased incidence of chronic pain after surgery, and the analgesic efficacy of ketorolac or clonidine when added to local anesthetics for intravenous regional anesthesia." Early COX-2-inhibiting drugs Celebrex (and other brand names for celecoxib) was introduced in 1999 and rapidly became the most frequently prescribed new drug in the United States. By October 2000, its US sales exceeded 100 million prescriptions per year for $3 billion, and was still rising. Sales of Celebrex alone reached $3.1 billion in 2001. A Spanish study found that between January 2000 and June 2001, 7% of NSAID prescriptions and 29% of NSAID expenditures were for COX-2 inhibitors. Over the period of the study, COX-2 inhibitors rose from 10.03% of total NSAIDs prescribed by specialty physicians to 29.79%, and from 1.52% to 10.78% of NSAIDs prescribed by primary care physicians (98.23% of NSAIDs and 94.61% of COX-2 inhibitors were prescribed by primary care physicians). For specialty physicians, rofecoxib and celecoxib were third and