Introduction: Azimilide hydrochloride is an investigational antiarrhythmic medication that had shown evidence of efficacy in prolonging the time to recurrence of atrial fibrillation (AF) or atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). This study was designed to confirm efficacy of 125 mg daily azimilide. Methods and Results: The primary endpoint was ECG‐documented recurrence of AF, AFL, or PSVT, followed for a maximum of 180 days. Four hundred eighty‐two patients were enrolled in the United States and Canada (422 with AF or AFL and 60 with PSVT). The primary efficacy analysis included 402 patients with AF‐AFL and 56 patients with PSVT. There was no significant difference in the time to first recurrence of symptomatic supraventricular arrhythmia in the AF‐AFL stratum (median of 38 days for azimilide versus 27 days for placebo; hazard ratio [HR] of 1.14, P = 0.29). Similarly, there was no difference in time to recurrence in the PSVT stratum (>180 days for azimilide versus 135 days for placebo; HR = 1.28, P = 0.55). There were three deaths in the azimilide group and one in the placebo group. Four patients had nonsustained ventricular tachycardia (one torsades de pointes), all in the azimilide group. Asymptomatic recurrence was frequent in the AF‐AFL group (8% with azimilide and 11% with placebo), but was absent in the PSVT group. False recurrence was common in both groups. Conclusion: Azimilide 125 mg daily was not associated with significant prolongation of the time to recurrent symptomatic supraventricular arrhythmias. There was substantial discordance between symptoms and recurrence.

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOx restricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.

Azimilide hydrochloride (azimilide), an investigational antiarrhythmic drug, has shown variable efficacy in preventing atrial fibrillation (AF). This study was designed to assess its efficacy in maintaining sinus rhythm in patients with paroxysmal AF and heart disease. Patients with symptomatic paroxysmal AF were screened for I month by transtelephonic monitoring. After recording I episode of AF in the screening period, they were randomized to receive azimilide 125 mg or placebo once daily. Patients were stratified by the presence or absence of congestive heart failure or coronary heart disease (CHF/CHD). A maximum of 220 patients without CHF/CHD were randomized, with the remainder having CHF/ CHD. Patients with CHF/CHD were monitored for 3 days during loading. The primary efficacy analysis was the time to the first symptomatic recurrence of AF in the CHF/CHD group. Secondary analyses were the time to the first recurrence in the entire population and the time to the first recurrence in those with significant structural heart disease. The median time to recurrence of AF in the CHF/CHD group was 10 days in the 2 treatment arms. Nonsignificant trends were seen toward efficacy of azimilide in the CHF/CHD group (hazard ratio 1.28, 95% confidence interval 0.97 to 1.70, p = 0.087), structural heart disease group (hazard ratio 1.22, 95% confidence interval 0.96 to 1.56, p = 0.11), and overall group (hazard ratio 1.22, 95% confidence interval 1.00 to 1.49, p = 0.053). No patient died. In conclusion, azimilide showed a nonsignificant trend toward efficacy in maintaining sinus rhythm in patients with AF. (c) 2006 Elsevier Inc. All rights reserved.

Specialized courses and mentored research projects are helping to revitalize the ranks of clinical researchers.

OBJECTIVE: To determine if a visual intervention [medication grid) delivered to physicians can reduce medication regimen complexity.DESIGN: Nonrandomized, controlled trial.SETTING: Veterans Affairs medical center.PATIENTS/PARTICIPANTS: Eight hundred thirty-six patients taking at least 5 medications at the time of admission and the 48 teams of physicians and students on the general medicine inpatient service.INTERVENTION: For intervention patients, a medication grid was created that displayed all of the patients' medicines and the times of administration for 1 week. This grid was delivered to the admitting resident soon after admission.MEASUREMENTS AND MAIN RESULTS: For the patients of each team of physicians, we calculated the change in the average number of medications and doses from admission to discharge. The number of medications in the Intervention group decreased by 0.92 per patient, and increased by 1.65 in the control group (P <.001). The mean number of doses per day in the intervention group decreased by 2.47 per patient and increased by 3.83 in the control group (P <.001).CONCLUSIONS: This simple intervention had a significant impact on medication regimen complexity in this population. Apparently, physicians were able to address polypharmacy when the issue was brought to their attention.

OBJECTIVES:The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both.BACKGROUND:Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem.METHODS:A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test.RESULTS:In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002).CONCLUSIONS:Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.

OBJECTIVE:To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD. DESIGN:Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half. SETTING:Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD). PARTICIPANTS:White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded. MAIN OUTCOME MEASURES:Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD. RESULTS:The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance. CONCLUSIONS:A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Almost 30 years have passed since the first measurement of regional cerebral blood flow in humans by 133Xe clearance. A review of the methodology is presented for the two-dimensional intracarotid method and the related inhalation and IV injection techniques. Emphasis is placed on the mathematical models employed and the blood flow indices derived from them. Similarities and differences between methods are described, and the contribution of each to clinical research is summarized.

Urine drug testing is gaining acceptance with employers nation-wide as a method of assuring a drug-free work environment. This article explains and discusses the currently used urine drug screening tests (EMIT, TLC, RIA and GCMS). Practical considerations involving specimen collection and proper chain of custody procedures are outlined. The legality of such tests and the legal and ethical issues of drug testing in the workplace are explored by reviewing precedent-setting court decisions. Labor's position on drug testing is summarized. The nurse practitioner responsible for establishing and/or administering company testing policy will benefit by a review of the scientific and legal issues involved in testing workers for drug use.

Objectives To evaluate the role of physical workload in low back pain (LBP) among adolescents. Methods Working history and physical workload factors at 18 years were assessed for 1984 members of the Northern Finland Birth Cohort 1986. The associations between work characteristics and LBP were analysed by multinomial logistic regression. Those with and without LBP at 18 years of age were compared in two subsamples. The incidence of LBP was studied among the 986 subjects without LBP at 16 years of age. Persistence of LBP was studied among the 728 subjects with LBP at 16 years of age. Latent class analysis (LCA) was used to form natural clusters of workload factors and their associations with LBP were investigated using log-binomial regression. Results 753 (75%) subjects without LBP at 16 years of age had been working during the 2-year follow-up period. The average duration of work was 6.2 months. In adolescent girls, working regularly or irregularly and duration of work exposure were associated with incident LBP. Of specific physical workload factors, only awkward trunk postures were associated with incident LBP in both genders (RR 1.2 in girls and 1.7 in boys). The work exposure patterns in adolescent girls and boys were different. In the LCA, subjects in a cluster with high exposure to awkward trunk postures or an overall physically demanding job had a higher likelihood of incident LBP in both genders (RR 1.3–1.9). None of the specific workload factors or clusters was associated with persistent LBP. Conclusions Physical workload factors constitute a risk for LBP even in adolescents.

A model utilizing computerized feedback to improve physician prescribing was studied in a family medicine residency practice. The frequency of generic prescribing was monitored for two sets of commonly used drugs: 21 “feedback” drugs and 13 “silent” drugs. After a four-month baseline period, the residents and faculty physicians were randomized into two groups. The experimental group received nine monthly printouts identifying “feedback” drugs they had prescribed by brand name with estimates of cost savings that might have been realized by generic prescribing. The control group received no feedback. Neither group received feedback regarding the “silent” drugs. Between the baseline and feedback periods, the increase in generic prescribing by experimental physicians was significantly greater than for control physicians for the “feedback” drugs as well as for the “silent drugs, indicating that the physicians generalized the message to prescribe generically.

A method is described for estimating the clearance rate and fractional blood flow of the fast (gray matter) compartment of the brain from the first ten minutes of 133Xe clearance curves, following a one-minute inhalation. Computer-simulated data were used to test the adequacy of the two-compartmental model employed, and to evaluate the stability of the parameters in the presence of random noise. A comparison was made between this approach and the previously reported three-compartmental analysis. Regional cerebral blood flow data were obtained on 48 young control subjects and 20 elderly demented patients. Hemispheral regional, and test-retest variations were determined, as well as differences between the groups.

Consider a discrete time Markov chain {Zn} whose state space is the non-negative integers and whose transition probability matrix ║Pij║ possesses the representation where {Pr}, r = 1,2,…, is a finite or denumerably infinite sequence of non-negative real numbers satisfying , and , is a corresponding sequence of probability generating functions. It is assumed that Z0 = k, a finite positive integer.