Obstetric Hemorrhage Education in the United States Survey of Current Efforts and Policy Options.

OBJECTIVE: To characterize efforts to improve obstetric hemorrhage education by state health departments and to evaluate them for guiding public policy. STUDY DESIGN: A survey with questions about maternal mortality/hemorrhage assessments and hemorrhage education for health professionals was emailed to public health officials in all 50 states. Follow-up phone calls and emails were sent over 5 months to maximize participation. A nationwide initiative for educating health professionals in treating chest pain was also examined. RESULTS: Responses were received from 34 states; 31 had legislative or regulatory requirements for identification and/or investigation of maternal deaths. Obstetric hemorrhage education among states is voluntary with the exception of Illinois, which had a regulatory require- ment. In contrast, a nationwide voluntary accreditation program for chest pain had over 1,000 accredited centers in the 10 years or so since being established. CONCLUSION: Only a few states had. voluntary efforts in place for obstetric hemorrhage education. A sin- gle state, Illinois, has a. mandatory education require- ment. A voluntary niodel of accreditation based on the example of Chest Pain Centers might serve as a faster way to provide education to large numbers of health pro- fessionals.

Effects of atomoxetine on growth in children with attention-deficit/hyperactivity disorder following up to five years of treatment.

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine. METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years. RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected weight by 36 months. Patients were slightly shorter than expected after 12 months, reaching a maximum shortfall at 18 months and returning to expected height by 24 months. Patients in the top quartile for body mass index (BMI) or weight at baseline, and those in the third quartile for height, showed 5-year decreases from expected values. Those below median height at baseline showed increases relative to expected values. CONCLUSIONS: These interim results indicate that continuous atomoxetine treatment for up to 5 years has little or no long-term effect on juvenile growth and final stature for most patients, although persistent decreases from expected may occur in some patients who are larger than average before treatment.

Comparison of extended-release metformin in combination with a sulfonylurea (glyburide) to sulfonylurea monotherapy in adult patients with type 2 diabetes: a multicenter, double-blind, randomized, controlled, phase III study.

BACKGROUND: Metformin is widely used in the management of type 2 diabetes, either as monotherapy or in combination with other oral antihyperglycemic agents such as sulfonylureas and thiazolidinediones. Combination treatment with metformin and sulfonylurea in patients who failed monotherapy has been reported to be effective in maintaining glycemic control. OBJECTIVE: The purpose for this study was to compare the efficacy and tolerability of extended-release metformin (MER) administered with a sulfonylurea (glyburide) to sulfonylurea monotherapy in patients with type 2 diabetes. METHODS: This multicenter, double-blind, randomized, controlled study enrolled adult patients with type 2 diabetes who were either drug naive or previously treated with oral diabetic medications and who had not achieved glycemic control. Patients were stabilized on sulfonylurea (10 mg/d for 2 weeks, then 15 mg/d for 4 weeks) then randomly assigned at base line to receive MER (1500 mg QD, 1000 mg BID, or 2000 mg QD) plus sulfonylurea (MER+S) or sulfonylurea monotherapy for 24 weeks. Patients were evaluated every 1 to 2 weeks during sulfonylurea stabilization and initial metformin treatment, and then every 4 weeks until study end. The primary efficacy end point was glycemic control as determined by changes in glycosylated hemoglobin (HbA(1c)) from baseline to study end between those receiving combination MER+S treatment and those receiving sulfonylurea monotherapy. Adverse events (AEs) were recorded throughout the study by direct questioning, self-reporting by patients, and from the results of physical examinations and clinical laboratory tests. RESULTS: A total of 741 patients were enrolled. Of these, 134 patients were stabilization failures, 607 patients were randomized, 575 patients received treatment and were included in the intent-to-treat population, and 417 patients completed the study per protocol. There were no significant differences between treatment groups for any demographic or baseline characteristics (all patients: mean [SD] age, 53.0 [10.6] years; male sex, 54.6% [314/575]; race, white, 58.8% [338/575], Hispanic, 28.5% [164/575]; mean [SD] weight, 97.0 [22.2] kg; obese [body mass index > or =30 kg/m(2)], 69.4% [399/575] ). There were significant decreases from baseline in mean fasting plasma glucose (FPG) levels by the end of week 1 and in mean HbA(1c) levels by week 8 in each MER+S group (both, P < 0.001). The mean (95% CI) changes from baseline to study end in the combined MER+S groups (HbA(1c), -0.74% [-0.85% to -0.64%]; FPG, -12.9 [-17.1 to -8.7] mg/dL) were significantly different from the sulfonylurea monotherapy group (HbA(1c), 0.08% [-0.08% to 0.25%]; FPG, 15.5 [8.2 to 22.8] mg/dL; P < 0.001). Among patients treated with MER+S, the mean (SEM) change in HbA(1c) was -1.26% (-1.44% to -1.07%) for drugnaive patients and -0.59% (-0.46% to 0.71%) for patients previously treated with metformin. There was a significant difference between treatment groups with regard to the prevalence of hypoglycemia (MER+S groups, 11.6% vs sulfonylurea monotherapy group, 4.2%; P = 0.007), but no significant difference was observed for gastrointestinal events. The most common gastrointestinal AEs were diarrhea and nausea (8.6% and 3.9%, respectively, in the combined MER+S groups; 2.8% and 1.4%, respectively, in the sulfonylurea monotherapy group). CONCLUSIONS: The combination of QD or BID treatment with MER+S was significantly more effective in lowering HbA(1c) and glucose levels than sulfonylurea monotherapy in these adult patients with type 2 diabetes. However, a significant increase in the prevalence of hypoglycemia was observed in the MER+S treatment groups compared with the sulfonylurea monotherapy group.

Placebo-controlled study of the effects of atomoxetine on bladder control in children with nocturnal enuresis.

INTRODUCTION: Nocturnal enuresis is a condition in which children at least 5 years of age are incontinent of urine at night. Atomoxetine, a potent inhibitor of the presynaptic norepinephrine transporter, is used to treat attention-deficit/hyperactivity disorder (ADHD). This study tested the hypothesis that atomoxetine will provide significant therapeutic benefit for nocturnal enuresis in patients with the diagnosis of nocturnal enuresis. METHODS: Atomoxetine's efficacy for improving nocturnal enuresis was studied in 87 pediatric subjects using an outpatient, multicenter, randomized, double-blind, parallel, placebo-controlled study. Efficacy was determined by measuring the mean number of dry nights per week using an intent-to-treat analysis of the primary outcome measure, the Dry Night Log-Parent Report (DNL-PR), a daily parent diary. RESULTS: Baseline and end point DNL-PR data were available from 42 atomoxetine-treated and 41 placebo-treated subjects. Atomoxetine increased the average number of dry nights per week by 1.47 compared with .60 for placebo (F = 7.06; df = (1, 75); p = 0.01). Fifteen atomoxetine-treated subjects (35.7%) had an increase of at least 2 dry nights per week compared with only 6 (14.6%) placebo-treated subjects (Fisher's exact test; p = 0.042). There were no significant differences in adverse events between the groups. CONCLUSIONS: Compared with placebo, atomoxetine treatment was associated with a significant increase in dry nights in children with nocturnal enuresis.

Comparison of the COX-inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of Osteoarthritis of the knee.

OBJECTIVE: To compare the efficacy, safety, and tolerability of AZD3582 with that of rofecoxib, naproxen, and placebo in patients with osteoarthritis (OA) of the knee, and to define the dosage of AZD3582 (125 mg, 375 mg, and 750 mg twice a day) that is noninferior in efficacy to rofecoxib. METHODS: A double-blind study of 672 patients with OA of the knee was conducted. Patients who experienced increased pain on withdrawal of analgesia were randomized to receive AZD3582 125 mg, 375 mg, or 750 mg twice a day; rofecoxib 25 mg once a day; naproxen 500 mg twice a day; or placebo for 6 weeks. Efficacy, tolerability, and safety were monitored throughout the study. The primary variable was the change in Western Ontario and McMaster Universities Osteoarthritis Index pain subscale from baseline to the mean of weeks 4 and 6, comparing AZD3582 with placebo for superiority and with rofecoxib for noninferiority using a predefined margin of 10 mm. RESULTS: For the primary variable, AZD3582 375 mg and 750 mg were superior to placebo (least squares mean difference [95% confidence interval] -12 mm [-18, -6], P < 0.001 and -13 mm [-19, -7], P < 0.001, respectively) and were noninferior to rofecoxib (-2 mm [-8, 4], P < 0.001 and -3 mm [-9, 3], P < 0.001, respectively). AZD3582 125 mg was not significantly different from placebo for the primary variable. CONCLUSION: AZD3582 375 mg and 750 mg twice a day were superior to placebo and as effective as rofecoxib 25 mg/day in treating the signs and symptoms of OA of the knee. AZD3582 125 mg twice a day was not statistically different from placebo.

Cardiovascular effects of atomoxetine in children, adolescents, and adults.

BACKGROUND: Atomoxetine is a highly specific presynaptic inhibitor of the noradrenaline (norepinephrine) transporter that was recently approved in the US for the treatment of patients with attention-deficit/hyperactivity disorder (ADHD). Adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, or cardiac rhythm have been associated with several noradrenergic medications. OBJECTIVE: To further elucidate the magnitude and impact of blood pressure and pulse elevations in patients taking atomoxetine. STUDY DESIGN: Short-term cardiovascular safety in children, adolescents, and adults with ADHD was assessed in five randomised, double-blind trials (duration up to 10 weeks) with atomoxetine (n = 612) or placebo (n = 474). Long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients who entered an open-label extension or a blinded continuation following short-term treatment. METHODS: Adverse events, blood pressure, sitting pulse, and electrocardiograms (ECGs) were collected throughout the trials. QT intervals were corrected for heart rate by a data-specific correction factor (QTcD; derived from baseline ECGs) as well as standard methods. RESULTS: Atomoxetine treatment was associated with small but statistically significant increases in mean systolic blood pressure in adults and diastolic blood pressure in children and adolescents. Mean pulse rate increased for all atomoxetine treatment groups. The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation. There was no significant difference between atomoxetine and placebo treatment groups in change in QTcD interval for all study populations. Palpitations in the adult patient population were the only significant cardiovascular adverse event (p = 0.037) occurring more frequently in the atomoxetine treatment group (3.7%) than in the placebo group (0.8%). Discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group. CONCLUSION: While atomoxetine has noradrenergic activity, increases in pulse and blood pressure were small and of little, if any, clinical significance. Atomoxetine was not associated with QT interval prolongation. Cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies.

Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone.