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Biomedical subjects

J Howes

Publications and source records attributed to J Howes.

At least 19 recordsLinked to original sources
PubMed2002

28-day oral toxicity study with soft corticosteroid BNP-166 in rats and dogs, followed by a 14-day recovery period.

The aim of the present study was to evaluate the soft corticosteroid BNP-166 in rats and dogs treated orally with 0.2, 2.0, and 20.0 mg/kg for 28 days and the reversibility of any abnormalities during a 14-day post-dosing period. The test substance, BNP-166, was well tolerated during the 28-day treatment period. The observed changes were all characteristic for the pharmacological actions of a glucocorticoid. Treatment related changes occurred in the adrenals and thymus, and, to a lesser extent, in the lymph nodes, spleen and liver. There were no statistically significant reductions in the cortisol levels of all groups in the 0.2 and 2 mg/kg treatments. Significant reductions were observed in the high-dose group (20 mg/kg), but levels returned to normal by the end of the 14-day recovery period. Based on the results, the No Observable Adverse Effect Level (NOAEL) of BNP-166 soft corticosteroid in rat and dog after 28-day oral administration is 2 mg/kg. This value is approximately 40 times higher than that of budesonide. Pharmacodynamic and receptor binding studies have shown BNP-166 to have a similar potency to budesonide; therefore, BNP-166 can be considered safer when administered orally than other corticosteroids such as prednisolone or budesonide.

Adrenal Cortex Hormones↗
PubMed2000

A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group.

A randomised, prospective, double-blind trial was performed, to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) Bemiparin and standard unfractionated heparin (UFH), for the prophylaxis of postoperative venous thromboembolism. 300 patients scheduled to undergo elective hip arthroplasty were included. The principal outcome measures were the incidence of thromboembolic events and bleeding complications. 149 patients received 3,500 anti-Xa IU of bemiparin plus a placebo injection daily and 149 patients received 5,000 IU of UFH twice a day. The two groups were similar with respect to factors likely to affect the risk of developing post-operative venous thromboembolism (VTE) and risk of bleeding events. During the post-operative period, 34 patients developed VTE complications; 9 (7.2%) in the bemiparin group and 25 (18.7%) in the UFH group. VTE in the two groups was statistically significant (OR of 2.96; 95% CI 1.32-6.62 and p = 0.01). There were no significant differences in the frequency of bleeding complications: major bleeding requiring discontinuation of prophylaxis, (OR 1.21; 95% CI 0.36-4.05; p = 1.00), the measured median operative blood loss (p = 0.77) or the median postoperative drain loss (p = 0.97), and the number of patients who developed wound haematoma (OR 0.87; 95% CI 0.31-2.46; p = 1.00). A comparison of coagulation parameters on the preoperative day with post-operative day 2 +/- 1, day 6 +/- 1 and day of discharge showed a significantly higher AT concentration, anti-factor Xa activity and TFPI levels in the bemiparin group when compared with UFH. This study demonstrates that bemiparin, in a single daily subcutaneous dose of 3,500 anti-Xa IU in high risk patients undergoing hip arthroplasty is more effective than UFH administered twice daily at a dose of 5,000 IU in the prevention of postoperative VTE. Both agents are equally safe.

Aged↗
PubMed1999

A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis.

OBJECTIVE: To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis. DESIGN: Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration. PARTICIPANTS: A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated. INTERVENTION: All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days. MAIN OUTCOME MEASURES: Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured. RESULTS: A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0-3 scale) and itching (3.4 vs. 3.0 units on a 0-4 scale) over the first 2 weeks. The treatment effect by these measures was -0.5 and -0.4 units in favor of LE (P < or = 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.

Adult↗
PubMed1998

A criterion-referenced measure of latex allergy knowledge.

The exponential use of latex products has increased patients' and health care workers' sensitization to natural rubber latex. The purpose of this research study was to develop and test a set of items designed to measure professional nurses' knowledge about natural rubber latex reactions and interventions appropriate for latex precautions. The items were developed from research reports in the literature and changed to reflect the suggestions offered by experienced perioperative nurses (pilot = 8) and three nationally known experts in latex allergy responses. The revised form was mailed to the home or distributed at the workplace of perioperative nurses (n = 158). Criteria for item retention were < .90 difficulty index and clinical relevance. Certified nurses (i.e., CNORs) scored significantly higher than other nurses who took the test at the same time (t-test = 2.00, P = .05). A pretest and posttest evaluation of the revised 20 items was conducted before and after a latex allergy continuing education program during the spring of 1998. The current knowledge test (i.e., version 1.1) has reliability (alpha = .80); content validity (CVI = .92); and accumulated evidence of construct validity (preinstruction mean = 14.16, postinstruction mean = 17.15, t-paired = 10.54, df = 70, P = < .001). An empirically developed professional nurse latex allergy competency test suitable for clinical use was the outcome of this research study.

Clinical Competence↗
PubMed1998

A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis.

BACKGROUND: Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy. OBJECTIVES: The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days. RESULTS: Enrolled were 133 patients (66 receiving loteprednol etahonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was -0.5 and -0.6 units in favor of loteprednol etabonate (P < .001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial.

Adult↗
PubMed1998

Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1.

PURPOSE: To compare the efficacy and safety of loteprednol etabonate 0.5% with those of a placebo (vehicle) in controlling anterior chamber cell and flare reaction in patients having cataract surgery with intraocular lens (IOL) implantation. METHODS: This randomized, double-masked, placebo-controlled, parallel-group multicenter study comprised patients who exhibited a minimum anterior chamber inflammation (ACI) score (sum of cell and flare reaction) of 3 (0 to 9 scale) on the day after cataract removal with posterior chamber IOL implantation. All 227 patients received loteprednol etabonate 0.5% or the placebo 4 times a day in the operated eye for up to 14 days after surgery. Five patients without valid on-treatment follow-up visits were not evaluated for efficacy. RESULTS: By the final visit, the ACI had resolved in 64% (70/109) of patients in the loteprednol etabonate group and 29% (33/113) of those in the placebo group (P < .001). The resolution rate and mean change from baseline of the individual components of ACI (cell and flare), as well as other signs and symptoms, was better in the loteprednol etabonate group. Both treatments were well tolerated. Among the 53 patients who did not complete the study, 34 (29%) were placebo patients discontinued for inadequate anti-inflammatory effect. The treatment failure rate and the time course of failures were lower in the loteprednol etabonate group; the differences were clinically meaningful and statistically significant (P < .001). Three patients in the loteprednol etabonate group had an intraocular pressure elevation of 10 mm Hg or more over the preoperative screening value. CONCLUSION: Loteprednol etabonate 0.5% led to a clinically meaningful reduction in the signs and symptoms of postoperative ACI and had an acceptable safety profile when compared with a placebo.

Adult↗
PubMed1998

Failure to detect systemic levels, and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration.

The objective of this study was to determine the systemic exposure to loteprednol etabonate (LE) following its chronic, ocular instillation. This was a randomized, double-masked, placebo controlled, single center trial in 14 normal volunteers. Subjects were randomly assigned to receive either LE (n=10) or placebo (n=4) and instructed to instill one drop into each eye 8 times daily on Days 0 and 1 and four times daily on Days 2 through 42. Blood levels of loteprednol etabonate (LE) and its major metabolite PJ-91 (delta1 cortienic acid etabonate) in plasma, and circulating plasma cortisol levels were measured during the study. Plasma levels of LE or PJ-91 were below the level of quantitation (1 ng/mL) for all subjects in both treatment groups. Plasma cortisol levels were all within the normal range. Chronic exposure to LE at a concentration and frequency equal to or greater than the intended therapeutic dose does not result in detectable systemic levels or hypothalamic pituitary axis suppression.

Adolescent↗
PubMed1998

The conjunctival provocation test model of ocular allergy: utility for assessment of an ocular corticosteroid, loteprednol etabonate.

Two studies were conducted using the conjunctival provocation test (CPT) model of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was loteprednol etabonate 0.5%, previously found effective in the treatment of ocular allergy and inflammation. The study was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i.d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic response received LE in one eye and placebo in the fellow eye for 28 days from Day 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline), 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vessel beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statistically significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the selection of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.1%, 0.2% and 0.3%, q.i.d. in 88 subjects. The dosing and testing regimen was similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0.2% and 0.3%, was numerically superior to the placebo in reducing mean redness and itching. At the 20-minute post allergen challenge, the 0.1% concentration was significantly superior (p < 0.05) to the placebo on Visit 4 (2 and 4 hour challenge) in reducing the mean redness; however, LE was only numerically superior in relieving itching. The 0.2% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness and itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness on all visits, and statistically significant in the reduction of itching on Visit 4 (4 hour challenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this model, 0.2% loteprednol etabonate was selected for further evaluation in environmental seasonal allergic conjunctivitis studies.

Adult↗
PubMed1998

Change in intraocular pressure during long-term use of loteprednol etabonate.

PURPOSE: Loteprednol etabonate is a novel site-active corticosteroid synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. In double-masked studies, loteprednol etabonate was effective in the treatment of giant papillary conjunctivitis, seasonal allergic conjunctivitis, postoperative inflammation, and uveitis. The objective of this analysis was to determine the incidence of clinically significant elevations in intraocular pressure (IOP) with long-term use of loteprednol etabonate. PATIENTS AND METHODS: All subjects (healthy volunteers or patients with inflammation or allergy) in all sponsored loteprednol etabonate studies in the United States were evaluated. A clinically significant elevation in IOP was defined as > or = 10 mmHg at any visit, and long-term use was defined as > or = 28 days. Of the 2,210 subjects, 1,648 were treated for 28 days or longer with loteprednol etabonate (0.2% or 0.5%), prednisolone acetate 1%, or vehicle. RESULTS: IOP elevation > or = 10 mmHg occurred in 1.7% (15/901) of patients taking long-term loteprednol etabonate, 0.5% (3/583) of those taking vehicle, and 6.7% (11/164) of those taking prednisolone acetate. Excluding patients who wore contact lenses, the incidence was 0.6% (4/624), 1.0% (3/304), and 6.7% (11/164) for loteprednol etabonate, vehicle, and prednisolone acetate, respectively. The incidence of IOP elevations with 0.2% loteprednol etabonate was 0.8% (1/133), similar to that for vehicle (0.7%, 1/135). CONCLUSION: The results of this analysis in a large population of subjects undergoing long-term therapy and of a previously published controlled, double-masked study in corticosteroid responders suggest that loteprednol etabonate has less propensity to cause clinically significant elevations in IOP than prednisolone acetate.

Androstadienes↗
PubMed1997

A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. The Loteprednol Etabonate Giant Papillary Conjunctivitis Study Group I.

PURPOSE: To evaluate the safety and effectiveness of loteprednol etabonate 0.5% ophthalmic suspension in reducing the ocular signs and symptoms accompanying contact lens-associated giant papillary conjunctivitis. METHODS: In a randomized, double-masked, placebo-controlled, parallel-group study conducted at 14 academic or private practice clinics, 223 adults with contact lens-associated giant papillary conjunctivitis received either loteprednol or the loteprednol vehicle (placebo), one drop, four times daily for 6 weeks. Papillae, itching, contact lens intolerance, other signs and symptoms of giant papillary conjunctivitis (O-to-3 or O-to-4 grade scales), and intraocular pressure were measured. RESULTS: The proportion of patients treated with loteprednol who at final visit demonstrated an improvement in papillae of at least one grade (78%, 85/109) was significantly greater than the proportion of those treated with placebo (51%, 56/110; P = .001). A treatment difference favoring loteprednol was seen with improvement in itching (95% vs 81%, 104/109 vs 89/110; P < .001) and lens intolerance (87% vs 77%, 95/109 vs 85/110; P = .053). Eight of 109 patients (7%, all taking loteprednol) had an intraocular pressure increase of 10 mm Hg or more on at least one visit during treatment. After discontinuation of loteprednol, intraocular pressure returned to normal levels. Both treatments were well tolerated, and no serious unexpected treatment-related medical events were reported. CONCLUSIONS: The rapid therapeutic response combined with the low incidence and transient nature of any intraocular pressure increase suggests that loteprednol is an appropriate treatment for giant papillary conjunctivitis.

Adolescent↗
PubMed1997

A controlled evaluation of the efficacy and safety of loteprednol etabonate in the prophylactic treatment of seasonal allergic conjunctivitis. Loteprednol Allergic Conjunctivitis Study Group.

PURPOSE: To evaluate the efficacy and safety of loteprednol etabonate 0.5% as prophylactic treatment for the ocular signs and symptoms of seasonal allergic conjunctivitis. METHODS: In this randomized, double-masked, placebo-controlled, parallel study, 293 adults with history of seasonal allergic conjunctivitis were treated with either loteprednol etabonate or vehicle (placebo) four times daily, beginning before the onset of the allergy season and continuing for 6 weeks. The primary efficacy measure was a primary composite score (sum of itching and bulbar conjunctival injection scores). Supportive efficacy measures were the investigator global assessment and a secondary composite score (sum of tearing, erythema, chemosis, and discomfort scores), all calculated during the 21-day peak pollen season. RESULTS: The proportion of patients who never developed moderate or severe signs and symptoms of allergy during the peak pollen season in the loteprednol etabonate treatment group was greater than that in the placebo group. For the primary composite score, this efficacy criterion was reached by 94% of patients (136/145) in the loteprednol etabonate group and 78% of patients (111/143) in the placebo group (P = .001). The magnitude of effect was similar for the investigator global assessment (86% [118/138] vs 64% [87/137]; P < .001) and, although not statistically significant, the secondary composite score (77% [112/145] vs 68% [97/143]; P = .092). None of the loteprednol etabonate-treated patients had an intraocular pressure increase of 10 mm Hg or more, whereas two placebo patients did. CONCLUSIONS: Loteprednol etabonate is generally effective in prophylaxis of seasonal allergic conjunctivitis and has an acceptable safety profile.

Adolescent↗
PubMed1997

A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis.

PURPOSE: To evaluate the safety and effectiveness of loteprednol etabonate 0.5% ophthalmic suspension (LE) for reducing the ocular signs and symptoms accompanying contact lens associated giant papillary conjunctivitis (GPC). We conducted a randomized, double-masked, placebo-controlled, parallel study at 11 U.S. academic or private practice clinics. METHODS: Two hundred and twenty adults with contact lens associated GPC were enrolled in this study. Patient were treated with either LE or the loteprednol etabonate vehicle (placebo), q.i.d. for 6 weeks. Papillae, itching, lens intolerance, as well as other signs and symptoms of GPC (0 to 3 or 0 to 4 point severity scales), and intraocular pressure were measured. RESULTS: The proportion of patients treated with LE demonstrating an improvement in papillae of at least one grade (75%) was significantly greater than the proportion of those treated with placebo (50%, P < 0.001). A treatment difference favoring LE was also seen with improvement in itching (92% vs. 76%, P = 0.001) and lens intolerance (84% vs. 66%, P = 0.002). Three patients (all on LE) had an intraocular pressure (IOP) elevation of 10 mm Hg or higher from baseline on at least one on-treatment visit. Cessation of therapy was required in one of these patients. CONCLUSIONS: Both treatments were well tolerated and no serious, unexpected, treatment-related medical events were reported. The rapid therapeutic response, combined with the low incidence, late development, and transient nature of any IOP elevation suggests that LE may be helpful in treating GPC.

Administration, Topical↗