Biomedical subjects

R W Hawkinson

Publications and source records attributed to R W Hawkinson.

10 recordsLinked to original sources

PubMed1992

Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.

Atrial Fibrillation↗

PubMed1991

Flecainide acetate prevents recurrence of symptomatic paroxysmal supraventricular tachycardia. The Flecainide Supraventricular Tachycardia Study Group.

Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1989

Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

Atrial Fibrillation↗

PubMed1989

Improved comfort and patient acceptance in a novel transdermal nitroglycerin delivery system.

Sixty-three angina patients were recruited to participate in a two-week, randomized, open-label, crossover, multicenter trial to compare patient acceptance of two transdermal nitroglycerin delivery systems, Minitran and Transderm-Nitro (TDN). Patients were enrolled if they had stable angina and had been on a stabilized dose (5, 10, or 15 mg/24 hr) of Nitro-Dur II (ND II) for at least one month before entering the study. Patients with a bias against TDN or with any of the contraindications for transdermal nitroglycerin therapy were excluded. During the two consecutive one-week treatment periods, the patients received their prestudy dose regimen of Minitran and TDN in random order. Patients completed daily diaries, weekly questionnaires, and poststudy patient preference evaluation forms. Of the 63 patients who completed the study, 70% preferred Minitran overall (P less than or equal to 0.001), 24% preferred TDN, and 6% had no overall preference.

Adhesiveness↗

PubMed1989

Improved skin adherence and patient acceptance in a new transdermal nitroglycerin delivery system.

Sixty-five patients with angina pectoris participated in a two-week, randomized, crossover, open-label, multicenter trial to compare patient preferences between two transdermal nitroglycerin delivery systems: Minitran and Nitro-Dur II (ND II). Patients were enrolled if they had stable angina pectoris and had been on a stabilized dose (5, 10, or 15 mg/24 hr) of Transderm-Nitro (TDN) for at least one month before entering the study. Patients with a bias against ND II or with any of the contraindications for transdermal nitroglycerin therapy were excluded. During the first one-week treatment period, the patients received their prestudy dose regimen of either Minitran or ND II. During the second week, the patients were crossed over to the transdermal delivery system that they had not received in the first week. Patients completed daily diaries, weekly questionnaires, and poststudy patient preference evaluation forms. Two patients, one in each treatment group, withdrew from the study because of increased angina, which was probably not related to the use of transdermal nitroglycerin. Fifty-seven percent of the patients preferred Minitran overall (P less than or equal to 0.05), 27% preferred ND II, and 16% had no overall preference.

Adhesiveness↗

PubMed1979

Methods of measuring zones of inhibition with the Bauer-Kirby disk susceptibility test.

Standard Bauer-Kirby disk tests were performed with 85 selected isolates, each tested in triplicate by four different investigators. Each disk test was observed, and zone diameters were measured, under two lighting conditions (transmitted light and reflected light). The two lighting systems produced similar zone measurements (+/-2 mm) with 96% of the tests. When there were greater differences, zones appeared to be larger when observed with reflected light. Interlaboratory reproducibility was much greater when using reflected light rather than transmitted light. We concluded that zone diameters should be measured from the back of the plate while it is resting on, or held 2 to 3 inches [ca. 5.1 to 7.6 cm] above, a black, nonreflecting, flat surface, illuminated by a reflected light source.

Anti-Bacterial Agents↗

PubMed1979

Simple inoculum standardizing system for antimicrobial disk susceptibility tests.

A collaborative study was undertaken to evaluate a simple, convenient device which expedites inoculum standardization for antimicrobial disk susceptibility tests. The Inocupac system (Minnesota Mining & Manufacturing [3M] Co., St. Paul, Minn.) was used to perform disk tests in parallel with the standard Bauer-Kirby method. Five investigators tested 100 selected isolates, each in triplicate. Inter- and intralaboratory precision of both disk procedures was essentially comparable. The Inocupac system failed to consistently provide satisfactory growth with some streptococci, but when testing common gram-negative bacilli, staphylococci, and most enterococci, the Inocupac system gave zones about the same size (+/-2 mm) as the Bauer-Kirby procedure. Interpretive agreement between the two test systems varied from 90 to 99% with different antimicrobial agents, and repeated tests with the Bauer-Kirby method demonstrated the same degree of interpretive agreement. The Inocupac system is a valid alternative method for inoculating disk susceptibility tests.

Anti-Bacterial Agents↗

PubMedDate not supplied

Performance of a new transdermal nitroglycerin adhesive patch formulation.

This two-period crossover study in 24 healthy men compared the transdermal absorption of nitroglycerin from a new 20-cm2 nitroglycerin adhesive transdermal patch applied for a single 24-hour period (q24hr) with that from one inch of 2% nitroglycerin ointment applied over a 50-cm2 area every eight hours (q8hr) during a single 24-hour period. The observed differences in pharmacokinetic parameters were expected, based on product design (q24hr vs q8hr) and surface area (20 cm2 vs 50 cm2); however, when corrected for surface area, the mean plasma AUC ratios indicated that the patch delivered about 1.5 times more drug than the ointment. The patch delivery of nitroglycerin was confirmed by patch residual results, which indicated nitroglycerin was released at a rate of 0.75 mg/cm2/24 hrs. The patch exhibited good skin adhesion throughout the 24-hour application period.

Administration, Cutaneous↗

PubMedDate not supplied

Drug release rates from four sizes of a new transdermal nitroglycerin adhesive patch.

This study was conducted to determine the amount of nitroglycerin released from transdermal nitroglycerin patches of four different sizes: 3.3 cm2, 6.7 cm2, 13.3 cm2, and 20 cm2. Thirty healthy men received a single 24-hour application of each patch size according to a randomized, open-label, four-period crossover design. A 24-hour interval separated each treatment period. The total amount of nitroglycerin released by the four patches was proportional to size. All four patch sizes released nitroglycerin at a comparable rate. The mean overall 24-hour release rate of 0.76 mg/cm2 was similar to the release rate of 0.75 mg/cm2/24 hr observed in a previous study. Adverse experiences common to nitroglycerin administration were reported for all patch sizes, with headache, light-headedness, and nausea reported most frequently.

Administration, Cutaneous↗

PubMedDate not supplied

Adhesion-to-skin performance of a new transdermal nitroglycerin adhesive patch.

Six men and six women participated in a study designed to compare adhesion-to-skin measurements of three transdermal nitroglycerin patch formulations (Minitran, Transderm-Nitro 5, and Nitro-Dur II) with an occlusive surgical tape control. After 24 hours of wear, Minitran was found to be superior to the other three products in skin adhesion. The force required to remove Minitran was significantly higher than that required to remove the other products. Maintaining good skin contact over the entire application period is essential for consistent drug delivery. Improved skin contact can increase transdermal drug delivery. This increase in delivery of nitroglycerin may result in the development of smaller patches rated to deliver the same quantity of nitroglycerin over a 24-hour period.

Adhesiveness↗