Twenty-Five Years' Experience and Beyond with Cultured Epidermal Autografts for Coverage of Large Burn Wounds in Adult and Pediatric Patients, 1989-2015.

This report summarizes the characteristics of 954 burned patients treated with cultured epidermal autografts (CEA), the largest number of patients to date. Data collected include patient demographics, survival, and final graft take. Source data were provided by the treating physician or attending burn team. Safety data were provided by the treating physician, attending burn team, and the pharmacovigilance database. In this dataset collected between 1989 and 2015, 954 patients were treated with cultured epidermal autographs for burns. Three hundred twenty-five (34%) were pediatric patients and 628 (66%) were adult (≥22 years of age); age unknown for one patient. The mean percentage total BSA (TBSA) burned was 67% (±17), median graft take at discharge was 75%, and overall survival at discharge was 84% (804/954). Survival rates were similar for pediatric and adult patients (89% vs 82%, respectively) and higher than the similar patient population reported in the National Burn Repository. Median graft take at discharge was also similar for pediatric and adult patients (80% vs 73%, respectively). The most frequently reported adverse reactions were infections in both pediatric and adult patients. There were no signals of increased risk of adverse reactions in pediatric compared with adult patients. When used as an adjunct to conventional split-thickness skin grafting for treatment of large burns in pediatric and adult patients, the analysis in this report shows an increased survival rate for patients treated with CEA compared with that reported for patients in the National Burn Repository with comparable burns.

A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics.

The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.

Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea.

OBJECTIVE: To compare the efficacy of the cyclooxygenase (COX)-2-specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea. METHOD: This single-center, double-blind, placebo-controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time-weighted sum of total pain relief, sum of pain intensity difference, time-specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re-medication, the percentage of patients taking rescue medication, and patient's global evaluation of study medication. RESULTS: Mean time-weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P <.01) and 40 mg (P <.001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference-12. Both doses of valdecoxib were well tolerated. CONCLUSIONS: Both valdecoxib 20- and 40-mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea.

The COX-2 selective inhibitor, valdecoxib, does not impair platelet function in the elderly: results of a randomized controlled trial.

The effects of the new cyclooxygenase (COX)-2 selective inhibitor, valdecoxib (40 mg bid; n = 17), on platelet function were evaluated, along with ibuprofen (800 mg tid; n = 15) and placebo (n = 15), in healthy elderly subjects (65-85 years) in this 7.5-day, randomized, single-center, double-blind study. Platelet aggregation (to sodium arachidonate, collagen, and adenosine diphosphate), bleeding time, and serum thromboxane B2 (TxB2) concentrations were measured up to 8 hours postdose on Days 1 and 8. Valdecoxib had no platelet effects, while ibuprofen significantly decreased platelet aggregation, significantly increased bleeding time (2-4 h postdose on each day), and significantly decreased TxB2 levels at all time points. In conclusion, unlike ibuprofen, valdecoxib 40 mg bid spares platelet COX-1 function in healthy elderly subjects. Valdecoxib's lack of effect on platelet aggregation and bleeding time suggests that it will have an improved clinical profile over nonselective NSAIDs, particularly in patients for whom bleeding complications are a concern.

The COX-2 specific inhibitor, valdecoxib, is an effective, opioid-sparing analgesic in patients undergoing total knee arthroplasty.

This multicenter, randomized, double-blind, placebo-controlled study evaluated the analgesic efficacy and opioid-sparing effects of valdecoxib, a potent COX-2 specific inhibitor, in patients undergoing knee replacement. Patients received morphine by patient-controlled analgesia (PCA), and valdecoxib 40 mg or 80 mg daily, or placebo, for up to two days. Efficacy was assessed by the cumulative amount of morphine administered over 48 hours, pain intensity and patient's evaluation of medication. Morphine consumption over 48 hours by patients receiving valdecoxib 40 mg or 80 mg daily plus morphine was 83.7% and 75.8% (P < 0.05) of the total amount consumed by patients receiving morphine alone. Patients receiving valdecoxib 40 mg and 80 mg daily experienced significantly lower maximum pain intensity on Day 2 (P < 0.05), and rated their study medication significantly higher than patients receiving morphine alone. Valdecoxib plus morphine was well tolerated. Thus, valdecoxib in combination with morphine provides multi-modal analgesia that reduces pain and opioid use and increases patient satisfaction following knee replacement surgery.

Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis.

OBJECTIVE: To determine whether valdecoxib, at chronic arthritis doses, has the characteristics of a cyclo-oxygenase 2 (COX-2) specific inhibitor, as measured by a reduced incidence of upper-gastrointestinal ulceration compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: This double-blind, multicentre, placebo-controlled, parallel-group study compared the incidence of gastroduodenal ulcers associated with valdecoxib 10 mg daily (q.d.) and 20 mg q.d. with that of ibuprofen 800 mg three times daily (t.i.d.) or diclofenac 75 mg twice daily (b.i.d.) when administered over a 12-week period. The incidence of gastroduodenal ulcers was assessed by upper-gastrointestinal endoscopy, performed at baseline and again at the end of week 12 (or at early study termination). Efficacy assessments were performed at baseline and at weeks 2, 6 and 12 using Patient's and Physician's Global Assessments of Arthritis. RESULTS: A total of 1052 osteoarthritis patients were enrolled into the trial. The incidence of gastroduodenal ulcers over 12 weeks was 5% in patients receiving valdecoxib 10 mg q.d., 4% in patients receiving valdecoxib 20 mg q.d., 7% in patients receiving placebo, 16% in patients receiving ibuprofen 800 mg t.i.d. (P <0.05 v. placebo), and 17% in patients receiving diclofenac 75 mg b.i.d. (P <0.05 v. placebo). The incidence of gastroduodenal ulcers at week 12 seen in the ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. groups was significantly higher than that in the valdecoxib 10 mg q.d. and valdecoxib 20 mg q.d. groups (P <0.05). The incidence rates of gastroduodenal ulcers were not significantly different between the valdecoxib treatment groups or between valdecoxib- and placebo-treated patients. Efficacy responses to valdecoxib 10 mg and 20 mg q.d. were significantly greater than placebo and comparable with both ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. CONCLUSIONS: The results of the study demonstrate that valdecoxib has an upper-gastrointestinal safety profile typical of a COX-2 specific inhibitor. Overall, the data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.

The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery.

BACKGROUND: The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase, or COX, -2-specific inhibitor, valdecoxib, with oxycodone/ acetaminophen in patients who have undergone oral surgery. METHODS: In total, 205 eligible subjects in Study A and 201 in Study B were randomized to receive a single oral dose of valdecoxib (20 or 40 milligrams), a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo. Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted. Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia. RESULTS: In both studies, subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and (among those who received valdecoxib 40 mg) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen. Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen. Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo. CONCLUSIONS: Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen, and it has a superior duration of analgesic effect in patients after oral surgery. Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen. CLINICAL IMPLICATIONS: The current standard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products. The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery.

Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis.

OBJECTIVE: We compared the efficacy and upper gastrointestinal safety of the cyclooxygenase-2-specific inhibitor valdecoxib with naproxen and placebo in treating moderate to severe osteoarthritis of the knee. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and upper gastrointestinal tract safety of valdecoxib at dosages of 5, 10, and 20 mg once daily with placebo and naproxen at the dosage of 500 mg twice daily. POPULATION: We included patients who had been diagnosed with moderate to severe osteoarthritis of the knee according to the modified criteria of the American College of Rheumatology. OUTCOMES MEASURED: The Patient's and Physician's Global Assessment of Arthritis (PaGAA, PhGAA), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), and Western Ontario and McMaster's Universities (WOMAC) Osteoarthritis indices were assessed at baseline and at weeks 2, 6, and 12. Upper gastrointestinal ulceration was assessed by pre- and posttreatment endoscopies. RESULTS: Valdecoxib 10 and 20 mg once daily (but not 5 mg once daily) demonstrated similar efficacy to naproxen at 500 mg twice daily, and all 3 dosages were superior to placebo for the PaGAA, PhGAA, PAAP-VAS, and WOMAC Osteoarthritis indices at most assessments throughout the 12-week study (P <.05). The incidence of endoscopically proven ulcers was significantly higher in the naproxen group than in the 5- and 10-mg valdecoxib groups, but not in the 20-mg valdecoxib group. All 3 valdecoxib doses were comparable to placebo in ulcer incidence. CONCLUSIONS: Valdecoxib (10 and 20 mg once daily) is significantly superior to placebo and as effective as naproxen (500 mg twice daily) in improving moderate to severe osteoarthritis of the knee. Upper gastrointestinal tract safety of valdecoxib (5 and 10 mg) was comparable to that of placebo and significantly better than that of naproxen.

Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty.

Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2-specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patient's global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients.

Valdecoxib does not impair platelet function.

The platelet effects of a supratherapeutic dose of the new cyclooxygenase (COX)-2 specific inhibitor, valdecoxib (40 mg twice a day), naproxen 500 mg twice a day, diclofenac 75 mg twice a day, and placebo were compared in 62 healthy adult subjects in this 7(1/2) day single-center, randomized, placebo-controlled trial. Platelet aggregation responses (to arachidonate [AA], collagen, and adenosine diphosphate [ADP]), bleeding time, and serum thromboxane B(2) (TxB(2)) concentrations were measured at baseline and at regular intervals on days 1 and 8. Valdecoxib had no effect on platelet function. Naproxen and diclofenac significantly reduced the platelet aggregation response to AA and to a lesser extent collagen and ADP at most assessments compared with placebo. Naproxen significantly lowered serum TxB(2) levels. In contrast to standard doses of 2 nonsteroidal antiinflammatory drugs (NSAIDs), a supratherapeutic valdecoxib dosage does not impair platelet function (COX-1). Valdecoxib may be a safer analgesic option than conventional NSAIDs in patients for whom bleeding complications are a concern. (Am J Emerg Med 2002;20:275-281.

Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen.

OBJECTIVE: Non-steroidal antiinflammatory agents are commonly used to treat pain and inflammation associated with osteoarthritis (OA), but have poor gastrointestinal (GI) tolerability. This study compared the efficacy of the COX-2 specific inhibitor valdecoxib with naproxen and placebo, in treating symptomatic OA of the hip. DESIGN: This multicenter, randomized, double-blind 12-week study compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg and 10 mg with placebo or naproxen 500 mg BID. Efficacy was assessed by Patient's and Physician's Global Assessment of Arthritis, and the WOMAC (Western Ontario and McMasters) OA Individual and Composite Indices. The incidence of adverse events was monitored throughout the study. RESULTS: Valdecoxib was clinically and statistically superior to placebo for Patient's and Physician's Global Assessment of Arthritis and for all WOMAC OA Indices over the 12 week study period (P

Valdecoxib is more efficacious than rofecoxib in relieving pain associated with oral surgery.

Inhibition of the cyclooxygenase (COX)-2 enzyme has been shown previously to reduce pain and inflammation. Valdecoxib is a new highly selective COX-2 inhibitor with a rapid onset of action and significant analgesic properties. This study compared the analgesic efficacy of valdecoxib and rofecoxib in treating postoperative pain in patients undergoing oral surgery. This randomized, double-blind, placebo-controlled study compared the efficacy of 40 mg valdecoxib with that of 50 mg rofecoxib and placebo. Efficacy was assessed by the onset of analgesia, pain intensity levels, and pain relief over 24 hours, time-weighted sum of total pain, sum of pain intensity difference, the percentage of patients requiring rescue medication and experiencing regimen failure, and patients' global evaluation. Patients receiving valdecoxib experienced a significantly quicker onset of analgesia, significantly improved pain relief, and lower pain intensity compared with patients receiving rofecoxib and greater satisfaction with their study medication after a single dose. Valdecoxib also demonstrated efficacy that was superior to that of rofecoxib with respect to the percentage of patients requiring rescue medication or experiencing regimen failure (p < or =.05). Valdecoxib, rofecoxib, and placebo were equally well tolerated. This study demonstrates that valdecoxib provides significantly greater analgesic efficacy than rofecoxib in the management of pain after oral surgery.

A single preoperative oral dose of valdecoxib, a new cyclooxygenase-2 specific inhibitor, relieves post-oral surgery or bunionectomy pain.

BACKGROUND: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. METHODS: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication. RESULTS: In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. CONCLUSIONS: Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.