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Biomedical subjects

Paul F Cavanaugh

Publications and source records attributed to Paul F Cavanaugh.

8 recordsLinked to original sources
PubMed2006

Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women.

OBJECTIVE: Prophylactic vaccination of 16- to 23-year-old females with a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine has been shown to prevent type-specific human papillomavirus infection and associated clinical disease. We conducted a noninferiority immunogenicity study to bridge the efficacy findings in young women to preadolescent and adolescent girls and boys, who represent a primary target for human papillomavirus vaccination. METHODS: We enrolled 506 girls and 510 boys (10-15 years of age) and 513 females (16-23 years of age). Participants were vaccinated on day 1, at month 2, and at month 6, and serology testing was performed on day 1 and at months 3 and 7 on blinded samples. Neutralizing antibody concentrations were determined using type-specific immunoassays and summarized as geometric mean titers and seroconversion rates. Vaccine tolerability also was assessed. RESULTS: By month 7, seroconversion rates were > or = 99% for all 4 human papillomavirus types in each group. By month 7, compared with women, anti-human papilloma virus geometric mean titers in girls or boys were noninferior and were 1.7- to 2.7-fold higher. Most (> 97%) injection-site adverse events were mild to moderate in intensity. Significantly more boys (13.8%) and girls (12.8%) than women (7.3%) reported fevers > or = 37.8 degrees C within 5 days of vaccination. Most (96.4%) fevers were mild (< 39 degrees C). CONCLUSIONS: Noninferior immunogenic responses to all 4 human papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human papillomavirus vaccination programs. This vaccine generally was well tolerated.

Adolescent↗
PubMed2005

Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: a 2-year randomized controlled clinical trial.

OBJECTIVE: To evaluate the immunogenicity, reactogenicity, and tolerability of a prototype human papillomavirus (HPV) 16 viruslike particle (VLP) vaccine directed against the L1 capsid protein. SUBJECTS AND METHODS: We enrolled healthy nonpregnant women aged 18 to 26 years into a 2-year, double-blind, dose-ranging multicenter trial (October 12, 1998, to September 30, 2001). Subjects were assigned to study groups to receive a 3-dose regimen (day 0, month 2, and month 6) of 1 of 4 vaccine doses: 10 microg, 20 microg, 40 microg, or 80 microg or placebo. Serum anti-HPV 16 L1 antibody (sL1Ab) geometric mean titers (GMTs) were measured at day 0, at month 3, at month 7, and every 6 months for a total of 2 years using a radioimmunoassay. The primary immunogenicity analyses evaluated GMTs at month 7 in L1Ab-seronegative subjects at baseline. Vaccine tolerability was also assessed. RESULTS: A total of 480 subjects were randomized to receive placebo (n=52) or 10 microg (n=112), 20 microg (n=105), 40 microg (n=104), or 80 microg (n=107) of HPV 16 L1 VLP vaccine. At baseline, 75% of subjects were L1Ab seronegative. All vaccine doses produced a statistically significant sL1Ab response vs placebo (P<.001). At the completion of the vaccination regimen, sL1Ab GMTs in baseline-seronegative subjects were 36- to 78-fold higher than the sL1Ab GMT at day 0 observed in subjects who had mounted an immune response to HPV 16 infection before enrollment. Serum L1Ab GMTs remained high throughout the 1.5-year postvaccination period. Postvaccination sL1Ab GMTs were 1.1- to 2.4-fold higher in women who had detectable sL1Ab levels at enrollment compared with those in baseline-seronegative subjects, particularly in the persistence phase. The vaccine was generally well tolerated with no statistically significant differences in injection site or systemic adverse experiences among treatment groups. CONCLUSION: Immunization with this novel HPV 16 L1 VLP vaccine was well tolerated and produced an immunogenic response that persisted for at least 1.5 years after the final dose.

Adolescent↗
PubMed2004

Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia.

PURPOSE: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. EXPERIMENTAL DESIGN: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. RESULTS: The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. CONCLUSION: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Etoricoxib.

Etoricoxib (Arcoxia, Merck & Co., Inc.) is a selective inhibitor of cyclooxygenase-2 (COX-2), an enzyme involved in pain and inflammation. It is a member of the COX-2-selective (coxib) class of nonsteroidal antiinflammatory drugs (NSAIDs). Extensive clinical trials have confirmed its analgesic and antiinflammatory efficacy to be at least as good as and in some cases superior to nonselective NSAIDs in a number of disease and patient treatment settings. Etoricoxib displays improved gastrointestinal safety compared with nonselective NSAIDs and has a favorable overall safety and tolerability profile. It is rapidly and completely absorbed following oral administration providing a rapid onset of action. Its long plasma half-life allows for once-daily dosing. Etoricoxib is currently approved in a number of countries for various indications including the treatment of acute pain, acute gouty arthritis, chronic low back pain, primary dysmenorrhea, and chronic treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis. In countries where it is approved, the highest recommended daily dose for chronic use is 90 mg for rheumatoid arthritis and 60 mg for osteoarthritis and chronic low back pain. The recommended daily dose for acute pain relief treatment from primary dysmenorrhea and acute gouty arthritis is 120 mg. This review summarizes the published preclinical and clinical data relevant to the use of etoricoxib in clinical practice.

Arthritis↗
PubMed2003

Relationship between age, renal function and bone mineral density in the US population.

Bisphosphonate drugs for treating osteoporosis are excreted by the kidney. However, many of the major trials on efficacy and safety of the bisphophonates for treating osteoporosis excluded patients with significant renal compromise. Since both osteoporosis and renal insufficiency become more prevalent with age, it seems prudent for physicians to be aware of the prevalence of renal dysfunction in patients with osteoporosis who are candidates for treatment with bisphosphonates. Data on 13,831 men and women aged 20+ from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) were used to study the occurrence of compromise in renal clearance function in men and women with osteopenia and osteoporosis. To estimate creatinine clearance (CCr), a measure of renal function, serum creatinine (sCr), weight and age were inserted into the Cockcoft-Gault (C-G) formula. The World Health Organization gender specific bone mineral density (BMD) cut-offs were used to define the populations with osteopenia and osteoporosis. For women ages 20-80+ with osteoporosis, the percent prevalence (95% CI) for mild to moderate compromise of CCr </=60 ml/min is estimated to be 85% (79%, 91%) and for severe renal compromise of CCr <35 ml/min to be 24% (19%, 29%). In women with osteoporosis and severe compromise, the age specific prevalence is negligible through ages 50-59 and then rises steeply to 54% (46%, 62%) for ages 80+. Similarly, in women with osteopenia and severe renal compromise, the age specific prevalence is also negligible through ages 50-59 and then rises to 37% (28%, 45%) for ages 80+. Lower prevalence estimates hold for men with about 11% of men with osteoporosis having severe renal compromise as compared to 24% for women. These data suggest that there is a substantial prevalence of candidates for treatment of osteoporosis and osteopenia who have significant renal compromise but for whom there is a dearth of clinical trial data on the impact of treatment.

Adult↗
PubMed2003

The overexpression of cyclo-oxygenase-2 in chronic periodontitis.

BACKGROUND: The objective of this prospective cross-sectional study was to determine if cyclo-oxygenase-2, or COX-2, is overexpressed in the inflamed gingival tissue of patients diagnosed as having moderate-to-severe chronic periodontitis, or CP. METHODS: The authors evaluated clinical measures, crevicular fluid and gingival biopsy specimens from patients with moderate or severe CP (n = 16) and from healthy volunteers (n = 8). Patients were diagnosed as having CP based on clinical attachment loss, or CAL, of at least 5 millimeters at two sites in each quadrant and on evidence of alveolar bone loss as assessed from standard periapical or bite-wing radiographs. Healthy patients exhibited no sites with CAL of more than 2 mm and no evidence of alveolar bone loss. The authors used standard techniques to perform biochemical measures. RESULTS: Levels of interleukin-1 beta, or IL-1beta, in crevicular fluid were more than doubled in the CP group (P < .05). The amounts of COX-2 mRNA and protein also were elevated in gingival tissues from subjects with CP compared with those from healthy subjects. To gain further mechanistic insights, the authors conducted in vitro studies. The results showed that lipopolysaccharide and tumor necrosis factor alpha, or TNF-alpha, induced COX-2 in macrophages, while IL-1beta and TNF-alpha induced COX-2 in oral epithelial cells. CONCLUSIONS: Taken together, these results suggest that levels of COX-2 in gingivae reflect clinical measures of periodontitis and gingival inflammation. CLINICAL IMPLICATIONS: The discovery of increased levels of COX-2 in inflamed gingival tissue suggests that COX-2 represents a pharmacological target for the prevention or treatment of CP.

Adult↗
PubMedDate not supplied

Evaluation of the effect of perioperative rofecoxib treatment on pain control and clinical outcomes in patients recovering from gynecologic abdominal surgery: a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND AND OBJECTIVES: In this randomized, placebo-controlled, double-blind study, the efficacy and safety of rofecoxib 50 mg was evaluated in patients undergoing major abdominal gynecologic surgery. METHODS: Patients were randomized to receive rofecoxib 50 mg (n = 81) or placebo (n = 83) approximately 2 hours before total abdominal hysterectomy or myomectomy and once daily over the ensuing 4 days. Clinical measurements included average daily opioid use over the 5-day period (primary endpoint), pain intensity on movement, and opioid-related side effects. RESULTS: Patients receiving rofecoxib required 32% less (P = .001) intravenous and oral opioids to relieve their postoperative pain from days 1 to 5 (primary endpoint), used 21% less (P = .011) on day 1, and 42% less (P < .001) from days 2 to 5. The rofecoxib group experienced less pain upon movement (P < .001), less sedation (P = .007), and a 24% reduction in the rate of antiemetic intake (P = .037) over the first 72 hours postsurgery. Earlier mean times to first flatus (-10.1 hours, P = .001), first bowel movement (-14.1 hours, P = .037), and time to hospital discharge (-10.9 hours; 95% confidence interval, -17.1 to -4.7) occurred in the rofecoxib group. There were no significant intergroup differences in blood loss, wound healing, or overall adverse experiences. CONCLUSIONS: Compared with placebo, perioperative administration of rofecoxib 50 mg provided significant opioid sparing, significantly better pain control, improved clinical outcomes, and was well tolerated.

Adult↗