Departures from the protocol during conduct of a clinical trial: a pattern from the data record consistent with a learning curve.

OBJECTIVE: Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinised. The VALsartan In Acute myocardial iNfarcTion, a large multinational, pragmatic, randomised, double-blind, multicentre trial, was retrospectively evaluated for evidence of research conduct consistent with a performance "learning curve". DESIGN: Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (eg, first, second), recruitment rate and first enrollment relative to study start date. SETTING: Computerised data from a trial coordinated by an academic research organisation collaborating with 10 academic and 2 commercial research organisations and an industry sponsor. Interventions 931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included patient's death or loss to follow-up within 12 months and subjects enrolled 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment and later start date. METHODS AND RESULTS: 12,367 patients at 931 sites were analysed. Departures were more common for patients enrolled earlier at a site (p<0.0001). For example, compared with the 30th patient, the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (p<0.0001). Similar patterns existed for queries. CONCLUSIONS: Research performance improved during the VALsartan In Acute myocardial iNfarcTion consistent with a "learning curve". Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality and economic implications for trial conduct.

Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation.

OBJECTIVE: To assess variables associated with the occurrence of atrial fibrillation (AF) and the relation of AF with short- and long-term outcomes and with other in-hospital complications in patients with acute coronary syndromes (ACS) with and without ST-segment elevation. DESIGN: Pooled database of 120 566 patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation (NSTE) ACS enrolled in 10 clinical trials. Multivariable logistic regression and Cox proportional hazards modelling were used to identify factors associated with AF and its relation with clinical outcomes. SETTING: ACS complicated by AF. PATIENTS: 120,566 patients with STEMI and NSTE-ACS in 10 clinical trials. INTERVENTIONS: None evaluated. MAIN OUTCOME MEASURE: Short- and long-term mortality. RESULTS: Occurrence of AF was 7.5% in the overall population (STEMI 8.0% (n = 84 161); NSTE-ACS = 6.4% (n = 36,405)). Seven-day mortality was higher for patients with AF (5.1%) than for those without (1.6%). After adjusting for confounders, association of AF with 7-day mortality was present in STEMI (hazards ratio (HR) = 1.65; 95% CI 1.44 to 1.90) and NSTE-ACS (HR = 2.30; 95% CI 1.83 to 2.90; p interaction = 0.015). Risk of long-term mortality (day 8 to 1 year) was also higher in STEMI (HR = 2.37; 95% CI 1.79 to 3.15) and NSTE-ACS (HR = 1.67; 95% CI 1.41 to 1.99). AF had a larger impact in NSTE-ACS on risk of short-term mortality (p<0.001), stroke (p<0.001), ischaemic stroke (p<0.001) and moderate or severe bleeding (p<0.001). CONCLUSIONS: AF is more common in patients with STEMI. An association of AF with short- and long-term mortality among patients with STEMI and NSTE-ACS was found. Understanding these findings may lead to better care of patients with this common arrhythmia.

[Sinus tarsi syndrome: what hurts?]. / Das Sinus-tarsi-Syndrom: Was schmerzt?

Sinus tarsi syndrome, described by O'Connor in 1958 and Brown in 1960, is a clinical finding often seen after an accident, consisting of a painful reaction to pressure on the sinus tarsi. This syndrome has also been described in dancers, volleyball and basketball players, overweight individuals, and patients with foot deformities (flatfoot). We looked for mechanical and functional macroscopic structures in the canalis and sinus tarsi that can be associated with sinus tarsi syndrome in order to deduce therapeutic consequences. We found a complex fibrous layer in the sinus and canalis tarsi that forms slips around the synovial sheats of the extensor tendons under the inferior extensor retinaculum. Both limbs run deep to the base of the sinus and canalis tarsi. The lateral band inserts into the sinus tarsi at the calcaneus, while the medial band inserts at the canalis tarsi at the talus and calcaneus. Instead of the term "interosseous ligaments," we recommend referring to the "fundiform ligament" with one lateral and one medial band. Regarding function, one can assume that the medial band of these fundiform ligaments controls the talus at eversion and inversion together with the well-vasculated and well-innervated interarticular fat pads in the sinus and canalis tarsi. While contracting the long extensor muscles of the toes, the ligament forms a control mechanism for the longitudinal arch of the foot in the moving phase.A question is how variations in vascularization or disorders in innervation will alter the turgor of the pads of fat tissue. That is, such alterations would influence the distribution of synovia in the neighboring joints as well as the tension of the involved ligaments.

[5-year follow-up study of total knee arthroplasty by means of EMG mapping]. / Nachuntersuchungsergebnisse mittels EMG-Mapping - 5 Jahre nach Knieendoprothesenimplantation.

AIM: The objective of the present study was to evaluate the long-term functional results after implantation of a total knee arthroplasty (TKA) objectively and quantitatively. METHOD: Functional parameters (muscular coordination, strength and range of motion) and the subjective satisfaction of the patients were measured by means of EMG mapping, isokinetics, ultrasound and a questionnaire in 21 patients with TKA 5.1 years after implantation of the TKA. RESULTS: 81 % of the investigated patients were subjectively satisfied. The isokinetic results showed a significant improvement of the extensor strength and of the relation between flexors and extensors. Patients who had been more physically active over these 5 years reached significantly better results. The results of EMG mapping showed good overall retention of the satisfactory coordination levels resulting from the initial in-patient rehabilitation. But the coordination patterns demonstrated clear changes showing highly activated areas in the region of the M. vastus medialis. The range of motion and the contraction capacity showed no further improvement compared with the results 26 weeks after implantation of the TKA. CONCLUSION: Long-term results after implantation of a TKA showed a good muscular coordination, strength and range of motion. A higher physical activity level led to better functional results and greater overall satisfaction of TKA patients 5 years after implantation.

Effect of eptifibatide on angiographic complications during percutaneous coronary intervention in the IMPACT--(Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis) II Trial.

We sought to determine whether eptifibatide reduces elevation of creatine kinase (CK)-MB isoenzyme release during coronary intervention by preventing angiographic complications, by minimizing the sequelae of angiographic complications once they occur, or by other mechanisms. In the Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis trial, patients underwent coronary intervention during treatment with placebo versus the glycoprotein IIb/IIIa receptor inhibitor eptifibatide. Eptifibatide decreased ischemic complications at 24 hours and 30 days. CK-MB elevations and in-laboratory angiographic complications (including major dissection, distal embolization, residual thrombus, abrupt closure, residual stenosis >50%, and side branch occlusion) were prospectively recorded. The incidence of any angiographic complication was lower in eptifibatide-treated patients (33%) than in placebo-treated patients (38%, p = 0.019). For patients with angiographic complications, there was a trend toward a reduced incidence of any elevation in CK-MB in the first 24 hours (29%, 135/0.75 eptifibatide dose; 33%, 135/0.5 eptifibatide dose; 37%, placebo). Among patients without angiographic complications, there was a similar trend toward fewer abnormal CK-MB levels in patients receiving eptifibatide (17% and 18% in eptifibatide arms vs 21% placebo). Thus, eptifibatide reduces angiographically evident complications during coronary intervention, but this effect accounts for only 1/3 of the reduced frequency of CK-MB elevations observed with eptifibatide. When angiographic complications occur, eptifibatide reduces rates of subsequent CK-MB elevation, accounting for another 1/3 of the reduction in CK-MB elevations. Finally, eptifibatide reduces the incidence of periprocedural CK-MB elevations in patients without angiographically evident complications, accounting for 1/3 of eptifibatide's overall effect in reducing of CK-MB elevations in patients undergoing percutanous coronary intervention.

Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials.

BACKGROUND: Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction. METHODS AND RESULTS: In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001). CONCLUSIONS: Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.

Cortisol and growth hormone responses to exercise at different times of day.

Exercise of appropriate intensity is a potent stimulus for GH and cortisol secretion. Circadian and diurnal rhythms may modulate the GH and cortisol responses to exercise, but nutrition, sleep, prior exercise patterns, and body composition are potentially confounding factors. To determine the influence of the time of day on the GH and cortisol response to acute exercise, we studied 10 moderately trained young men (24.1 +/- 1.1 yr old; maximal oxygen consumption, 47.9 +/- 1.4 mL/kg.min; percent body fat, 13.2 +/- 0.6%). After a supervised night of sleep and a standard meal 12 h before exercise, subjects exercised at a constant velocity (to elicit an initial blood lactate concentration of approximately 2.5 mmol/L) on a treadmill for 30 min on 3 separate occasions, starting at 0700, 1900, and 2400 h. Blood samples were obtained at 5-min intervals for 1 h before and 5 h after the start of exercise; subjects were not allowed to sleep during this period. Subjects were also studied on 3 control days under identical conditions without exercise. There were no significant differences with time of day in the mean blood lactate and submaximal oxygen consumption values during exercise. The differences over time in serum GH and cortisol concentrations between the exercise day and the control day were determined with 95% confidence limits for each time of day. Exercise stimulated a significant increase in serum GH concentrations over control day values for approximately 105--145 min (P < 0.05) with no significant difference in the magnitude of this response by time of day. The increase in serum GH concentrations with exercise was followed by a transient suppression of GH release (for approximately 55--90 min; P < 0.05) after exercise at 0700 and 1900 h, but not at 2400 h. Although the duration of the increase in serum cortisol concentrations after exercise was similar (approximately 150--155 min; P < 0.05) at 0700, 1900, and 2400 h, the magnitude of this increase over control day levels was greatest at 2400 h. This difference was significant for approximately 130 min and approximately 40 min compared to exercise at 1900 and 0700 h, respectively (P < 0.05). The cortisol response to exercise at 0700 h was significantly greater than that at 1900 h for about 55 min (P < 0.05). A rebound suppression of cortisol release for about 50 min (P < 0.05) was observed after exercise at 2400 h, but not 0700 or 1900 h. Both baseline (before exercise) and peak cortisol concentrations were significantly higher at 0700 h than at 1900 or 2400 h (P < 0.01). We conclude that time of day does not alter the GH response to exercise; however, the exercise-induced cortisol response is modulated by time of day.

Sex differences in neurological outcomes and mortality after cardiac surgery: a society of thoracic surgery national database report.

BACKGROUND: The purpose of this study was to evaluate whether women undergoing cardiac surgery are more likely to suffer neurological complications than men and whether these complications could explain, at least in part, their higher perioperative mortality. METHODS AND RESULTS: The Society of Thoracic Surgery National Cardiac Surgery Database was examined for the years 1996 and 1997 to determine the frequency of new neurological events (stroke, transient ischemic attack, or coma) occurring after cardiac surgery. We reviewed clinical information on 416 347 patients (32% women) for whom complete neurological outcome data were available. New neurological events after surgery were higher for women than for men (3.8% versus 2.4%, P=0.001). For the whole group, the 30-day mortality was higher for women than for men (5.7% versus 3.5%, P=0.001), and among those patients who suffered a perioperative neurological event, mortality was also significantly higher for women than men (32% versus 28%, P=0.001). After adjustment for other risk factors (eg, age, history of hypertension and/or diabetes, duration of cardiopulmonary bypass, and other comorbid conditions) by multivariable logistic regression, female sex was independently associated with significantly higher risk of suffering new neurological events after cardiac surgery (OR 1.21, 95% CI 1.14 to 1.28, P=0.001). CONCLUSIONS: Women undergoing cardiac surgery are more likely than men to suffer new perioperative neurological events, and they have higher 30-day mortality when these complications occur. The higher incidence of perioperative neurological complications in women cannot be explained by currently known risk factors.

Outcome of acute ST-segment elevation myocardial infarction in patients with prior coronary artery bypass surgery receiving thrombolytic therapy.

BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001). CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.

Electrophysiologic and clinical effects of angiotensin-converting enzyme inhibitors in patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. MUSTT Investigators. Multicenter UnSustained Tachycardia Trial.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden cardiac death and all-cause mortality. They also may have direct antiarrhythmic properties. We retrospectively analyzed the data from the Multicenter UnSustained Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on inducibility of sustained ventricular tachycardia and on sudden cardiac death and overall mortality in 2,087 patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. Results of electrophysiologic testing were compared by use of ACE inhibitors at baseline, and outcomes were compared between the 564 patients prescribed ACE inhibitors at discharge and the 1,523 patients who did not receive treatment. The inducibility of sustained ventricular tachycardia during electrophysiologic testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75). Patients discharged from hospital on ACE inhibitors had a lower ejection fraction, more extensive coronary artery disease, and fewer previous revascularizations at baseline. After adjustments for differences in baseline factors and initial hospitalization variables, there were no significant differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow-up.

Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators.

BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to

Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators.

BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Prediction of 1-year survival after thrombolysis for acute myocardial infarction in the global utilization of streptokinase and TPA for occluded coronary arteries trial.

BACKGROUND: When a patient survives thrombolysis for acute myocardial infarction, little information from large studies exists from which to estimate prognosis during follow-up visits. METHODS AND RESULTS: Baseline, in-hospital, and later survival data were collected from 41 021 patients enrolled in Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries, a randomized trial of 4 thrombolytic-heparin regimens with standard aspirin and beta-blockade. Cox proportional hazards models were developed to predict 1-year survival in 30-day survivors (n=37 869) from baseline clinical and ECG factors and in-hospital factors; a combined model then was developed (C-index 0.800). The model was simplified into a nomogram to predict individual outcomes (C-index 0.754). Factors reflecting demographics (advanced age, lighter weight), larger infarctions (higher Killip class, lower blood pressure, faster heart rate, longer QRS duration), cardiac risk (smoking, hypertension, prior cerebrovascular disease), and arrhythmia were important predictors of death between 30 days and 1 year. Black race was associated with a substantial increase in risk after considering other factors. Revascularization was associated with reduced risk between 30 days and 1 year. CONCLUSIONS: When evaluating a patient who has survived acute infarction treated with thrombolysis, clinicians can estimate the likelihood of survival from factors easily measured during admission. Although many risk factors clearly relate to age, left ventricular dysfunction, or clinical instability, black race is an unexplained risk factor requiring further examination.

Application of a continuous regression model of restenosis to saphenous vein grafts after successful percutaneous transluminal coronary angioplasty or directional coronary atherectomy.

OBJECTIVES: To evaluate a quantitative model of restenosis in patients with vein graft disease undergoing percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). BACKGROUND: A quantitative relationship between acute gain and late loss has been developed to describe the late changes in lumen dimension after native vessel coronary intervention. This same relationship may also be seen after treatment of saphenous vein graft disease. METHODS: Patients with native coronary artery stenoses (CAVEAT-I) or saphenous vein graft lesions (CAVEAT-II) were randomized to either DCA or PTCA, and data from these trials were analyzed retrospectively. Angiographic results of the target lesions were reviewed, and each lesion was assessed for vessel caliber and reference diameter, absolute minimal lumen diameter, percent diameter stenosis, percent stenosis of the cross-sectional area, acute gain and late loss. Linear regression models were used to determine late loss and to detect differences in angiographic outcomes. RESULTS: Vein grafts had significantly larger reference vessel diameters than native coronary arteries; they also had significantly more acute gain and more late loss. Directional coronary atherectomy was associated with a larger acute gain in both studies. Patients undergoing DCA also experienced greater late loss although the effect was statistically significant only in the CAVEAT-I study. After adjusting for the acute gain, the treatment effect on late loss became nonsignificant in both studies. CONCLUSIONS: In patients undergoing DCA or PTCA of saphenous vein graft narrowings, the relationship between late loss and acute gain is also demonstrated, similar to the device-independent relationships seen in native coronary lesions. In CAVEAT-II, larger degrees of acute gain were also associated with higher degrees of late lumen loss.

Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.

Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators.

BACKGROUND: Ventricular septal defect (VSD) complicating acute myocardial infarction has been studied primarily in small, prethrombolytic-era trials. Our goal was to determine clinical predictors and angiographic and clinical outcomes of this complication in the thrombolytic era. METHODS AND RESULTS: We compared enrollment characteristics, angiographic patterns, and outcomes (30-day and 1-year mortality) of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with and without a confirmed diagnosis of VSD. Univariable and multivariable analyses were used to assess relations between enrollment factors and the development of VSD. In all, 84 of the 41 021 patients (0.2%) developed VSD, a smaller percentage than reported in the prethrombolytic era. The median time from symptom onset to VSD diagnosis was 1 day. Enrollment factors most associated with this complication were advanced age, anterior infarction, female sex, and no previous smoking. The infarct artery was more often the left anterior descending and more likely to be totally occluded in patients who developed VSD. Mortality at 30 days was higher in patients with VSDs than in those without this complication (73.8% versus 6.8%, P<0.001). Patients with VSDs selected for surgical repair (n=34) had better outcomes than patients treated medically (n=35; 30-day mortality, 47% versus 94%). CONCLUSIONS: Compared with historical control subjects, patients who undergo thrombolysis within 6 hours of infarction onset may have a reduced risk of later VSD. If patients develop this mechanical complication, however, it typically occurs sooner than described in the prethrombolytic era. Despite improvements in medical therapy and percutaneous and surgical techniques, mortality with this complication remains extremely high.

Morphological investigations of connective tissue structures in the region of the nervus occipitalis major.

The connective tissue lamellae surrounding the n. occipitalis major are arranged in such a way that they form at least two compartments. An outer epineurial, and an inner endoneurial one. The outer compartment is a shifting and sliding layer, the inner one is probably filled with fluid which means that it is relatively incompressible. This fluid could be drawn off and supplied through the widely branched arterial and venous reticulum, the vasa nervorum. Measurements of the connective tissue space area (perineurium, subperineurial space, endoneurium with axon and glia) on the n. occipitalis major showed a high correlation between measured values. In addition, lammellar corpuscles of the Paccini type are regularly found in both compartments. These receptors measure the local pressure and shearing forces. The design of the suspension network along with the course of the muscles in the area of the regio occipitalis, the interdependence of the connective tissue compartments, the diffusion barrier of the perineurium, the mighty vasa nervorum and the occurrence of lamellar corpuscles, all point to a probable connection with the symptom complex of occipital neuralgia.

Effect of age on outcome with primary angioplasty versus thrombolysis.

OBJECTIVES: The purpose of this study was to determine how risks associated with increasing age differed in patients treated with percutaneous transluminal coronary angioplasty versus thrombolysis. BACKGROUND: Advancing age is a risk factor for adverse outcome in patients with acute myocardial infarction. Primary angioplasty has been thought to be particularly beneficial in higher risk patients including the elderly. There is, however, limited data on any differential incremental benefit of angioplasty compared with thrombolysis in candidates for either treatment. METHODS: In the GUSTO-IIb angioplasty substudy, 1,138 patients were randomized to receive primary angioplasty or accelerated tissue-type plasminogen activator (t-PA). The effect of age on outcome was assessed as a discrete and continuous variable for each treatment group. Models using age as a linear factor as well as cubic spline transformations were used for the major end points of 30-day death or disabling stroke; death or reinfarction; and death, reinfarction or disabling stroke. RESULTS: For each 10-year patient group, outcome was improved with angioplasty (n = 565) compared with t-PA (n = 573). Irrespective of treatment, however, risk increased with age. After adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or myocardial infarction by 1.32 (95% confidence interval 1.04 to 1.76, p = 0.022). For all adverse outcomes, this incremental effect of increasing age was constant. CONCLUSIONS: Advancing age is associated with worse outcomes, and the risks increase in proportion to age. Although primary angioplasty improves outcomes over thrombolysis, it does not appear to be more beneficial in older than in younger patient groups. The incremental adverse effect of age does not vary by treatment strategy.

Is all unstable angina the same? insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I). The CAVEAT-Investigators.

BACKGROUND: Certain characteristics of unstable angina have been associated with worse clinical outcomes after percutaneous revascularization procedures. METHODS AND RESULTS: We compared outcomes of patients with (n = 690) and those without (n = 320) unstable angina in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) by unstable angina subgroup: rest chest pain, postinfarction chest pain, chest pain with ischemic electrocardiographic changes, chest pain with recent acceleration, and no chest pain. Regression models were constructed to predict in-hospital and 6-month composite end point death, infarction, bypass surgery, percutaneous revascularization, and abrupt closure (in-hospital) or restenosis (6 months) for each subgroup. Only chest pain with electrocardiographic changes predicted the composite in-hospital outcome (24% vs 17% with no chest pain, P =.0374.) This subgroup also had a greater acute gain, more late loss, and more restenosis than patients in the other subgroups. Rest chest pain carried a higher incidence of the composite 6-month outcome (39.9% vs 29% with no chest pain, P =.0472). For all unstable angina categories, atherectomy was associated with worse overall outcomes than angioplasty. CONCLUSIONS: Patients with unstable angina have more complications of percutaneous revascularization than patients without unstable angina, but event rates vary by anginal subgroup. The clinical presentation may help to identify unstable angina patients at particularly high risk for adverse outcomes.