Retrospective analysis of the incidence of epidural haematoma in patients with epidural catheters and abnormal coagulation parameters.

BACKGROUND: Epidural haematoma is a rare but potentially catastrophic complication associated with epidural catheterization. The times of insertion and removal of epidural catheters are high-risk periods for epidural haematoma formation, especially with abnormal coagulation parameters. There is a lack of data on the incidence of epidural haematoma in patients with abnormal coagulation parameters. METHODS: A retrospective analysis was undertaken from 2002 to 2009 on patients with an epidural catheter. Queries were performed on the coagulation parameters for the dates of placement and removal of the catheters and on all documented epidural haematoma cases. RESULTS: During the study period, 11 600 epidural catheters were placed. In the setting of abnormal coagulation parameters, 278 (2.4%) epidural catheters were placed and 351 (3%) were removed. Two epidural haematomas occurred; both patients had epidural catheters and spinal drains placed for vascular procedures with abnormal coagulation parameters after operatation. The haematomas occurred after removal of the catheters. Based on our study, the incidence of epidural haematoma in patients with abnormal coagulation parameters is 1 in 315 patients, with the lower limit of the 95% confidence interval at 87 and the upper limit at 2597. CONCLUSIONS: The risk of epidural haematoma is clearly elevated with abnormal coagulation parameters. Our data suggest that as the incidence of epidural haematoma with neuraxial access in patients with abnormal coagulation is not 100%, individual risk-benefit evaluations are warranted.

Hepatitis C treatment among racial and ethnic groups in the IDEAL trial.

Previous studies of chronic hepatitis C virus (HCV) treatment have demonstrated variations in response among racial and ethnic groups including poorer efficacy rates among African American and Hispanic patients. The individualized dosing efficacy vs flat dosing to assess optimaL pegylated interferon therapy (IDEAL) trial enrolled 3070 patients from 118 United States centres to compare treatment with peginterferon (PEG-IFN) alfa-2a and ribavirin (RBV) and two doses of PEG-IFN alfa-2b and RBV. This analysis examines treatment response among the major racial and ethnic groups in the trial. Overall, sustained virologic response (SVR) rates were 44% for white, 22% for African American, 38% for Hispanic and 59% for Asian American patients. For patients with undetectable HCV RNA at treatment week 4, the positive predictive value of SVR was 86% for white, 92% for African American, 83% for Hispanic and 89% for Asian American patients. The positive predictive values of SVR in those with undetectable HCV RNA at treatment week 12 ranged from 72% to 81%. Multivariate regression analysis using baseline characteristics demonstrated that treatment regimen was not a predictor of SVR. Despite wide-ranging SVR rates among the different racial and ethnic groups, white and Hispanic patients had similar SVR rates. In all groups, treatment response was largely determined by antiviral activity in the first 12 weeks of treatment. Therefore, decisions regarding HCV treatment should consider the predictive value of the early on-treatment response, not just baseline characteristics, such as race and ethnicity.

Analysis of pelvic fracture pattern and overall orthopaedic injury burden in children sustaining pelvic fractures based on skeletal maturity.

PURPOSE: The purpose of this study was to review pelvic fractures and concomitant orthopaedic injuries in children who have a patent triradiate cartilage (TRO) compared with children whose triradiate cartilage has closed (TRC). We hypothesise that these injuries will differ, leading to correlated alterations in management. PATIENTS AND METHODS: Using a database, we retrospectively reviewed patients aged below 18 years with pelvic fractures presenting to our Level 1 trauma center. Radiographs and CT scans were reviewed to identify orthopaedic injuries and categorise pelvic injuries using the modified Torode classification between the two groups. RESULTS: A total of 178 patients met inclusion criteria (60 TRO and 118 TRC). Mean age ± SD for TRO and TRC groups were 8 ± 4 years and 16 ± 2 years, respectively. TRO patients were more likely to present as a pedestrian struck by a vehicle (odds ratio (OR) 6.0; p < 0.001) and less likely to present after a motor vehicle collision (OR 0.2; p < 0.001). TRO patients were more likely to sustain rami fractures (OR 2.1; p = 0.020) and Torode IIIA injuries (OR 3.6; p < 0.001). They were less likely to sustain acetabular fractures (OR 0.5; p = 0.042), sacral fractures (OR 0.4; p = 0.009), hip dislocations (p = 0.002) and Torode IV injuries (OR 0.4; p = 0.004). TRO patients were less likely to be treated operatively for their pelvic (OR 0.3; p = 0.013) and orthopaedic injuries (OR 0.4; p = 0.006). CONCLUSION: We suggest that patients with open triradiate cartilage are unique. Their pelvic injuries may be treated more conservatively as they have a greater potential for periosteal healing and bone remodelling. Patients with closed triradiate cartilage should be treated similarly to adults, as they share a similar mechanism of injury and need for operative fixation.

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.

BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.

Prostaglandin E2 analogue elicits renal and hormonal compensatory mechanisms in human hypertension.

Endogenous prostaglandin E2 appears to play an important role in cardiovascular homeostasis. When administered exogenously, it is a potent vasodilator, but the requirement for intravenous administration and its short duration of action have limited studies to its acute effects. A novel prostaglandin E2 analogue, CL 115347, can be administered transdermally on a long-term basis. The cardiovascular responses to the chronic administration of CL 115347 were studied in a double-blind, placebo-controlled trial in 26 subjects with essential hypertension (16 given drug, 10 placebo) maintained on a 100-mEq sodium diet. Administration of CL 115347 produced a fall in diastolic blood pressure of 7.8 +/- 1.3 mm Hg, compared with a 2.3 +/- 1.7 mm Hg fall in controls (p = 0.02), with no change in heart rate. The direct vascular effect of the drug was confirmed by attenuation of the vasoconstrictor response to angiotensin II infusion (13.4 +/- 3.1 vs 21 +/- 2 mm Hg at 3.0 ng/kg/min; p less than 0.05). However, the chronic blood pressure effect of CL 115347 was modest. Subjects receiving active drug showed significant compensatory increases in plasma renin, aldosterone, and norepinephrine levels accompanied by sodium retention and kaliuresis. In summary, chronic administration of this prostaglandin E2 analogue resulted in a modest decrease in blood pressure and antagonism of angiotensin II-mediated vasoconstriction. However, its effects were largely offset by compensatory increases in vasoconstrictor hormones and sodium retention.

Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension.

The 24-h blood pressure control of bisoprolol, a new beta-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3, 8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p < 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p < or = 0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1, 7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Toward strategies for the analysis of periodontal disease clinical trials.

We consider design, analysis and regulatory issues relating to clinical trials in periodontal disease and identify complications commonly associated with such studies. Alternative statistical procedures that can be used for the analyses of data from periodontal research are reviewed and a case study of the analysis of a Phase II periodontal disease clinical trial is provided to illustrate the use of one of these procedures.

Design of clinical trials for chronic diseases: implications for periodontal disease.

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.

Reproducibility and comparability of a computerized, self-administered food frequency questionnaire.

A self-administered dietary assessment questionnaire was developed for the microcomputer to identify individuals whose dietary patterns may put them at risk for cancer. It was tested among 50 adult volunteers in a New York school district. The quantitative food frequency portion of the questionnaire (FFQ), administered twice one month apart, was reproducible for calories, fat, percentage of calories from fat, cholesterol, vitamin A, vitamin C, calcium, and dietary fiber (Spearman r = 0.56-0.87). To test for relative validity, individual nutrient intake calculated from each administration of the FFQ was compared with the nutrient intake calculated from seven-day food records collected one month after the second FFQ administration. Nutrient intake from the first and second FFQ compared with food record nutrient intake yielded a Spearman's correlation coefficient of 0.58 and 0.62, respectively, for percentage of kilocalories from fat. No significant difference in mean intake of percentage of calories from fat was found between the FFQ 1 and FFQ 2 or between the FFQs and the food record. However, there were significant differences between mean food record and FFQ estimates of kilocalories, fat, vitamin A, vitamin C, calcium, and dietary fiber. We concluded that computerized nutrient assessment, which utilizes the subject in data entry, may be suitable for some clinical and educational uses and research studies of intake of fat as a percentage of calories among healthy adults.

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

BACKGROUND: A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin. METHODS: 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. FINDINGS: The SVR rate was significantly higher (p=0.01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. INTERPRETATION: In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.