Safety culture and the 5 steps to safer surgery: an intervention study.

BACKGROUND: Improvements in safety culture have been postulated as one of the mechanisms underlying the association between the introduction of the World Health Organisation (WHO) Surgical Safety Checklist with perioperative briefings and debriefings, and enhanced patient outcomes. The 5 Steps to Safer Surgery (5SSS) incorporates pre-list briefings, the three steps of the WHO Surgical Safety Checklist (SSC) and post-list debriefings in one framework. We aimed to identify any changes in safety culture associated with the introduction of the 5SSS in orthopaedic operating theatres. METHODS: We assessed the safety culture in the elective orthopaedic theatres of a large UK teaching hospital before and after introduction of the 5SSS using a modified version of the Safety Attitude Questionnaire - Operating Room (SAQ-OR). Primary outcome measures were pre-post intervention changes in the six safety culture domains of the SAQ-OR. We also analysed changes in responses to two items regarding perioperative briefings. RESULTS: The SAQ-OR survey response rate was 80% (60/75) at baseline and 74% (53/72) one yr later. There were significant improvements in both the reported frequency (P<0.001) and perceived importance (P=0.018) of briefings, and in five of the six safety culture domain scores (Working Conditions, Perceptions of Management, Job Satisfaction, Safety Climate and Teamwork Climate) of the SAQ-OR (P<0.001 in all cases). Scores in the sixth domain (Stress Recognition) decreased significantly (P=0.028). CONCLUSIONS: Implementation of the 5SSS was associated with a significant improvement in the safety culture of elective orthopaedic operating theatres.

Quality of life instruments and definitions in individuals with spinal cord injury: a systematic review.

STUDY DESIGN: A systematic review. OBJECTIVE: To critically review quality of life (QOL) instruments used with spinal cord injury (SCI) populations. SETTING: Vancouver, Canada. METHODS: A systematic literature review was conducted for publications assessing the measurement properties of QOL outcome measures. Pre-established criteria were used to evaluate the measurement properties. RESULTS: Fourteen articles reporting on 13 QOL instruments met the inclusion criteria, including the Patient Reported Impact of Spasticity Measure (PRISM), Quality of Well-being Scale, Qualiveen, Sickness Impact Profile (SIP68), Short Form (SF)-36, SF-36V, SF-12, SF-6D, Quality of Life Index, Quality of Life Profile for Adults with Physical Disabilities (QOLP-PD), Satisfaction with Life Scale, Sense of Well-being Index (SWBI), and the World Health Organization Quality of Life-BREF scale (WHOQOL-BREF). The SF-36 and WHOQOL-BREF have been widely used and validated. The SIP68, QOLP-PD, SF-36V, and SWBI are promising with limited investigation. The Qualiveen and PRISM performed well and are specific to SCI complications. CONCLUSION: The WHOQOL-BREF is presently the most acceptable and established instrument to assess QOL after SCI. The SIP68, QOLP-PD, SF-36V, and SWBI are promising; however, require further evaluation of their measurement properties.

Digit ratio (2D:4D) and sprinting speed in boys.

Digit ratio (2D:4D), a putative correlate of prenatal testosterone, has been found to relate to performance in sport and athletics such that low 2D:4D (high prenatal testosterone) correlates with high performance. Speed in endurance races is strongly related to 2D:4D, and may be one factor that underlies the link between sport and 2D:4D, but nothing is known of the relationship between 2D:4D and sprinting speed. Here we show that running times over 50 m were positively correlated with 2D:4D in a sample of 241 boys (i.e. runners with low 2D:4D ran faster than runners with high 2D:4D). The relationship was also found for 50 m split times (at 20, 30, and 40 m) and was independent of age, BMI, and an index of maturity. However, associations between 2D:4D and sprinting speed were much weaker than those reported for endurance running. This suggests that 2D:4D is a relatively weak predictor of strength and a stronger predictor of efficiency in aerobic exercise. We discuss the effect sizes for relationships between 2D:4D and sport and target traits in general, and identify areas of strength and weakness in digit ratio research.

Evaluation of right atrial and biatrial temporary pacing for the prevention of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVES: The purpose of this study was to determine if atrial pacing is effective in reducing postoperative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation after coronary artery bypass grafting (CABG) is a common problem for which medical management has been disappointing. Atrial-based pacing has become an attractive nonpharmacologic therapy for the prevention of AF. METHODS: Sixty-one post-CABG patients (mean age = 65 years) were randomized to one of three groups: no atrial pacing (NAP), right atrial pacing (RAP) or biatrial pacing (BAP). Each patient had one set of atrial wires attached to both the right and left atria, respectively, at the conclusion of surgery. Patients in the RAP and BAP groups were continuously paced at a rate of 100 pulses per minute for 96 h or until the onset of sustained AF (>10 min). All patients were monitored with Holter monitors or full disclosure telemetry to identify the onset of AF. The primary end point of the study was the first onset of sustained AF. RESULTS: There was no significant difference in the proportion of patients developing AF in the three groups (NAP = 33%; RAP = 29%; BAP = 37%; p > 0.7). However, for the subset of patients on beta-adrenergic blocking agents after CABG, there was a trend toward less AF in the paced groups. There were no serious complications related to pacing, although in three patients the pacemaker appeared to induce AF by pacing during atrial repolarization. CONCLUSIONS: Continuous right or biatrial pacing in the postoperative setting is safe and well tolerated. We did not find that post-CABG pacing prevented AF in this pilot study; however, the role of combined pacing and beta-blockade merits further study.

Monokines mediate decreased hepatic glucocorticoid binding in endotoxemia.

The purpose of this study was to determine whether endotoxin decreased hepatic glucocorticoid binding by the action of mediator(s). Steroid binding in liver cytosol, plasma glucose levels, and plasma corticosterone levels were assayed in C3HeB/FeJ LPS normoresponsive and C3H/HeJ LPS hyporesponsive mice. In C3HeB/FeJ mice, endotoxin significantly depressed the maximum number of steroid binding sites (Bmax) to 30% of control. Plasma glucose levels were decreased to 50% of control, and plasma corticosterone levels increased 4-fold. No changes in these parameters were seen in C3H/HeJ mice given endotoxin, except for decreased plasma glucose levels at the highest dose of endotoxin. Decreased steroid binding was observed in C3H/HeJ mice 4-6 hours after receiving C3HeB/FeJ peritoneal exudate cells (elicited with thioglycolate) and endotoxin. No change in steroid binding was observed in C3H/HeJ mice that received C3H/HeJ peritoneal exudate cells and endotoxin. Mediator-rich plasma was produced in CF-1 mice by infecting them with 1 X 10(7) BCG and by challenging them with endotoxin (2 micrograms) 2 weeks later for 2 h. Transfer of BCG-endotoxin plasma to C3H/HeJ mice also resulted in decreased steroid binding and plasma glucose. These results indicate that perturbation of glucocorticoid action during endotoxin shock is mediated by soluble factor(s) other than endotoxin. A likely source of mediator(s) is the mononuclear phagocyte.

Decreased expression of murine PPARgamma in adipose tissue during endotoxemia.

Infection-induced hyperlipidemia develops due to a combination of factors, one of which is decreased clearance of lipids from the bloodstream due to depressed synthesis of lipoprotein lipase (LPL). Recently, the peroxisome proliferator activated receptors (PPARs) have been shown to be important in the regulation of LPL, particularly PPARgamma. PPARgamma and its heterodimerization partner, RXR alpha have been shown to be transcriptional activators of LPL in co-transfection analysis. Therefore, we hypothesized that the decrease in LPL expression during endotoxemia may be a result of depressed PPARgamma expression. In these studies, we examined the effect of endotoxin or its proximal mediator, tumor necrosis factor (TNF), on the expression of PPARgamma in white (WAT) and brown adipose tissue (BAT) in CD-1 mice. We report that treatment with endotoxin, but not TNF, transiently decreased PPARgamma mRNA levels 4 hr after treatment. However, endotoxin or TNF treatment decreased PPARgamma protein levels after 18 hr, which was at a time when LPL mRNA levels were also depressed. These data suggest that decreased PPARgamma expression following endotoxin or TNF treatment may contribute to the hyperlipidemia due to decreased expression of LPL, which would impair triglyceride clearance.

Erratic eye tracking in schizophrenic patients as revealed by high-resolution techniques.

Using high-resolution infrared oculography with digital recording and analysis techniques, we tested several types of eye movements in 19 schizophrenic patients and 11 normal controls. Abnormal slow pursuit eye movements, seen in about half of the patients, were characterized by erratic inaccuracies in position, velocity, and phase. Tracking errors were quantitatively assessed by their root mean square (RMS) error. Position RMS errors fell into two clearly separated groups, with 10 of 19 patients clustering about the normal controls and the remaining 9 having much higher errors than normal. Although several of these poor trackers had an excess of saccades or low pursuit gain, these abnormalities were not primarily responsible for the large erratic tracking errors. Saccades in response to unpredictable target jumps had normal latencies (reaction times) and velocities, but were more hypometric and variable in accuracy than those of controls. These saccadic abnormalities did not correlate with the patients' position RMS errors during slow pursuit.

Monitoring glucocorticoid therapy: a pharmacokinetic approach.

Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6-hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens.

Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma.

Plasma histamine, cortisol, epinephrine, cyclic adenosine monophosphate (cAMP), and leukocyte beta-adrenergic receptors were measured in asthmatic patients with (n = 7) and without (n = 10) nocturnal asthma at 4 PM and 4 AM and compared with those of normal subjects (n = 10). A twofold higher plasma histamine concentration was observed at 4 AM compared with 4 PM in all groups, with no change in plasma cortisol, epinephrine, and cAMP concentrations. At 4 AM compared with 4 PM, only patients with nocturnal asthma had a significant 33% decrease (p less than 0.05) in mononuclear and polymorphonuclear leukocyte beta-adrenergic receptor density, with no difference in binding affinity in all three groups. Polymorphonuclear leukocytes from patients with nocturnal asthma had significantly impaired response to isoproterenol at 4 AM (17% +/- 7.3% SEM increase in cAMP; p less than 0.05) compared with those of patients without nocturnal asthma (69.4% +/- 13.7%) and normal (80.2% +/- 21.3%) subjects. A significant change in beta-adrenergic receptor density and function occurs at night in patients with nocturnal asthma.

Nuclear hormone receptors and adipogenesis.

Adipocytes provide a model cell system for exploring the complexities of nuclear hormone receptor transcriptional regulation. Adipocytes produce lipid and cholesterol metabolites which can serve as activating ligands for many of the classic and "orphan" nuclear hormone receptors. At the same time, nuclear hormone receptors directly control adipocyte commitment. The recently described nuclear hormone receptor coactivators and corepressors provide an additional level of complexity to this system. This review emphasizes available in vitro and in vivo models and discusses them in the context of current controversies and future experimental directions.

Dual-site atrial pacing for atrial fibrillation in patients without bradycardia.

Atrial pacing has been shown to delay the onset of atrial fibrillation (AF) when compared with ventricular pacing in patients with sick sinus syndrome. The role for pacing in the control of AF in patients without bradycardia is uncertain. We performed a randomized, crossover, single-blinded study in 22 patients (14 women, aged 63 +/- 10 years) with paroxysmal AF refractory to treatment with oral sotalol (202 +/- 68 mg/day) and no bradycardic indication for pacing. All patients received a dual-chamber pacemaker with 2 atrial pacing leads positioned at the high right atrium and coronary sinus ostium, respectively. Patients were randomized in a crossover fashion to be paced for 12 weeks, either with high right atrial (RA) pacing at 30 beats/min ("Off") or dual-site RA pacing with an overdrive algorithm that maintained atrial pacing at a rate slightly above the sinus rate ("On"). Treatment on resulted in a significantly higher percentage of atrial pacing and a reduction in atrial ectopic frequency than the treatment off period. The time to the first clinical AF recurrence was prolonged (15 +/- 17 to 50 +/- 35 days, p = 0.006), and total AF burden was reduced (45 +/- 34% vs 22 +/- 29%, p = 0.04) in the on-treatment phase. However, there was no difference in AF checklist symptom scores or overall quality-of-life measures. Dual-site RA pacing with continued sinus overdrive prolonged the time to AF recurrence and decreased AF burden in patients with paroxysmal AF. The absence of a major impact on symptom control suggests that pacing should be used as an adjunctive therapy with other treatment modalities for AF.

Randomized prospective pilot study of long-term dual-site atrial pacing for prevention of atrial fibrillation.

OBJECTIVE: To determine whether dual-site atrial pacing is feasible, safe, and effective. DESIGN: We undertook a randomized prospective single-blind crossover study. MATERIAL AND METHODS: Nine patients with at least two episodes per month of symptomatic paroxysmal atrial fibrillation participated in a randomized crossover study involving three separate 3-month blocks of single-site atrial pacing, dual-site atrial pacing, and control (support-only) pacing. RESULTS: Dual-site atrial pacing resulted in shorter P wave duration (81 +/- 14 ms) than did single-site pacing (111 +/- 12 ms) or control sinus rhythm (123 +/- 9 ms) (P<0.0001) and in fewer premature atrial complexes on Holter monitoring (P = 0.06). The arrhythmia-free interval was longer with dual-site pacing (67 +/- 17 days) than with single-site (62 +/- 30 days) or support-only (49 +/- 34 days) pacing (P = 0.10). This pilot study was not statistically powered to detect a difference between pacing modes. CONCLUSION: (1) Dual-site atrial pacing is feasible and safe; (2) it shortens the P wave duration and tends to decrease premature atrial complexes on Holter monitoring; (3) any atrial pacing tends to prolong the arrhythmia-free interval; and (4) this pilot study enrolled too few patients to determine whether a significant difference in pacing modes exists and supports the need for a larger study.

Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug. Comparison of spirometry with methacholine challenge.

Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.

Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma.

STUDY OBJECTIVE: To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma. MATERIALS AND METHODS: This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group. RESULTS: Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups. CONCLUSION: Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.

Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma.

The bronchodilator effect of nebulized AMN, albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children. In phase 1, maximal bronchodilation was determined by dose-response studies on separate days. Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2. In phase 1, 0.11 +/- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation. In phase 2, the peak response to albuterol occurred within 30 min and to AMN, at 60 min. Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol. AMN FEV1 response was better than for placebo for 3 h; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus, the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children, but the combination may extend the period of bronchodilatation.

Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells.

Recently ouabain has been shown to induce transcription of proto-oncogenes in different cell types. In the present study, we examined the effect of ouabain on the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and the cell number, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to proliferating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-oncogenes within 1 h. This latter response disappeared after 24 h. The number of cells significantly increased in response to low concentrations of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in response to higher concentrations of the agent, probably due to a toxic effect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. According to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic effect of ouabain on VSMCs may be a component of this hypertensive action.

Comparative analysis of Haemophilus influenzae type b and Escherichia coli J5 lipopolysaccharides.

Haemophilus influenzae type b (HIB) and Escherichia coli J5 (J5) lipopolysaccharides (LPS) were examined to explore the basis of previously observed cross-protection. HIB-LPS and J5-LPS contained ketodeoxyoctonate, glucose, glucoheptose and glucosamine as common carbohydrate moieties, and laurate, myristate, beta-hydroxymyristate and palmitate as common fatty acids, although in different ratios. J5-LPS was five times more lethal than HIB-LPS for chick embryos. Weak serological cross-reactivity was observed by haemagglutination and two-dimensional immunoelectrophoresis. No significant cross-reactivity was demonstrated by enzyme-linked immunosorbent or toxicity-neutralisation assays. The cross-reactivity observed between HIB-LPS and J5-LPS was probably due to common components in the core glycolipid.

Bradycardia induced by intravascular versus direct stimulation of the vagus nerve.

BACKGROUND: Electrical stimulation of the parasympathetic nervous system results in slowing of the heart. We sought to determine whether cardiac vagal efferent axons can be stimulated adequately to induce bradycardia without disturbing the integrity of the thorax. METHODS: Cardiodepressor effects elicited by direct stimulation of a vagus nerve in anesthetized dogs and pigs were compared with those generated when the same nerve was stimulated indirectly through bipolar electrodes placed in the adjacent superior vena cava. RESULTS: The heart rate of dogs decreased by about 80% when electrical stimuli were delivered to the right thoracic vagus at the level of the thoracic outlet through bipolar electrodes placed either in the adjacent superior vena cava (intravascular method) or directly on the nerve (direct method). Maximal responses were achieved with 10-V, 5-ms, and 20-Hz stimuli. In anesthetized pigs, similar bradycardia occurred when the right cervical vagus or the right cranial thoracic vagus was stimulated either directly or indirectly through the intravascular method. Atrial dysrhythmias occurred when the stimulating electrodes were placed by either method within 1 cm of the right atrium in both animal models. CONCLUSIONS: Controlled bradycardia can be induced during operation without the risk of generating cardiac dysrhythmias using electrical stimuli (10 V, 5 ms, and 10 to 20 Hz) delivered to the right cervical vagus nerve or the right cranial thoracic vagus nerve through adjacent intravascular electrodes.

Effect of low-dose troleandomycin on theophylline clearance: implications for therapeutic drug monitoring.

Troleandomycin (TAO) is an alternative agent used in the treatment of severe, steroid-requiring asthma. Its mechanism of action, once thought to be inhibition of theophylline clearance, remains unclear. Twenty-four-hour theophylline profiles were obtained in 11 children with severe asthma prior to and after 2 and 12 weeks of low-dose TAO therapy. Theophylline dosages were adjusted by blinded investigators to maintain serum theophylline concentrations (STCs) between 10 and 20 micrograms/ml. Dosages were decreased from 877 +/- 60 mg/day (mean +/- SEM) before TAO to 811 +/- 56 mg/day (NS) after 2 weeks and 764 +/- 56 mg/day (p less than 0.05) after 12 weeks. Because of the dosage adjustments, STCs did not increase significantly. Theophylline clearance was reduced from 65.7 +/- 9.8 ml/kg/hour at baseline to 50.2 +/- 4.1 ml/kg/hour (p less than 0.05) after 2 weeks and 50.1 +/- 6.2 ml/kg/hour (p less than 0.05) after 12 weeks of TAO therapy. We conclude that TAO can significantly reduce theophylline clearance, resulting in increased STCs if dosages are not titrated. We recommend an empiric 25% reduction of daily theophylline dose with the initiation of TAO. We also recommend monitoring STCs 4 hours after the morning dose (with twice-daily dosing of sustained-release products) after 3, 7, 14, and 30 days of TAO therapy, then periodically as indicated.

Design and implementation of the Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) clinical trial. DAPPAF Phase 1 Investigators.

The Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) study compares dual site, single site and support pacing modalities in the prevention of atrial fibrillation (AF) in patients with a history of paroxysmal AF (PAF) and a bradyarrhythmic indication for pacing. The trial is a randomized crossover comparison of dual site atrial pacing, single site atrial pacing, and a support pacing control period (DDI at 50 ppm or VDI) done in six month intervals. Patient inclusion requires at least 2 documented AF episodes in the three months prior to enrollment. The patients can be on concurrent antiarrhythmic drug regimens but this regimen must remain constant throughout the protocol. Patients with AV nodal ablation are excluded from this study. The primary endpoints of the study compare the time to first recurrence of clinically significant symptomatic AF with ECG verification, and quality of life among the three treatment modes. Secondary endpoints include time to first recurrence of all AF episodes as monitored by the pacemaker, the measurement of echocardiographic parameters, and symptoms logged by the patients. This trial was designed after pilot studies showed dual site pacing to be safe, feasible and preliminary results suggested increased maintenance of sinus rhythm with atrial pacing.