Dose Of Streptokinase Research Articles

Case report: Intra arterial thrombolysis with iv line can save an acutely ischemic limb

Case report: Intra arterial thrombolysis with iv line can save an acutely ischemic limb

A Comparative Study of the Safety and Efficacy of Intrapleural Fibrinolysis With Streptokinase and Urokinase in the Management of Loculated Pleural Effusions.

BackgroundIntrapleural fibrinolytic therapy (IPFT) with streptokinase (STK), urokinase (UK), and alteplase remains a common practice for managing loculated pleural effusions (LPEs). However, very limited data are available on the comparative efficacy of these agents.MethodologyWe compared the efficacy and safety of intrapleural streptokinase (n = 28) and urokinase (n = 38) in 66 patients with loculated effusions. IPFT was initiated if effusion remained undrained despite the placement of intercostal chest drainage or pigtail catheter. The dose of STK and UK were 250,000 IU twice daily and 100,000 IU once daily, respectively. The volume of fluid drained after IPFT, radiologic response, clinical response, and adverse events were compared between the two groups.ResultsThe mean volume of fluid drained post-IPFT was 1,379 mL in the STK arm and 1,110 mL in the UK arm (p = 0.251). Of the 66 patients, 53 (80.3%) had good clinical response, and 28 (43.7%) had >75% resolution of effusion on chest radiographs. The clinical (79% vs. 82%; p = 0.765) and radiologic response rates (39.3% vs. 44.6%; p = 0.568) were similar in both STK and UK arms. Pain was the most common adverse event in both groups. Significantly more patients in the STK arm developed fever (14% vs. 0%, p = 0.030). Treatment-limiting adverse events occurred in five patients.ConclusionsIPFT is a safe and effective method for managing patients with LPEs. Although the clinical and radiologic response rates were similar with STK and UK, the latter may be the preferred choice because of its better safety profile and ease of administration (once-daily dose).

RESULT OF SLOW INFUSION OF STREPTOKINASE THERAPY IN LEFT SIDED PROSTHETIC VALVE THROMBOTIC OCCLUSION- A CASE SERIES FROM A TERTIARY CARE HOSPITAL IN EASTERN INDIA

Prosthetic valve thrombosis (PVT) is a life threatening complication seen after heart valve replacement and is associated with high mortality and morbidity. Surgical approach or brinolysis and heparin therapy are considered as treatments of choice according to the clinical status of the patient. Thrombolytic therapy has been tried in cases with acute prosthetic valve thrombosis as an alternative to emergency operation with variable results. But fear of peripheral embolism has limited its use in left-sided valve occlusions. The incidence of complications decreases with low dose and slow infusion of brinolytic therapy. In this study we are presenting our experience of thrombolytic therapy with streptokinase in 40 patients who had presented with acute or subacute left-sided prosthetic valve thrombosis. In this study the mean age was 40.9 years (SD-11.2, range-19 to 64 year) with majority (77.5%) were below 50 year of age. Duration of valve replacement was 2.95 ± 1.74 years (1 to 7 years). Average time of presentation since onset of symptoms was 4.75 ± 2.77 days (1 to 12 days). Majority was presented with NYHA class IV symptoms (22/40) and 50% patients presented with cardiogenic shock. 85% patients had atrial brillation and the anticoagulation status was inadequate in 62.5% cases. Overall aortic valve involvement was 37.5% (15 patients) and mitral valve involvement was 62.5% (25 patients). Average mean gradient for aortic valve was 64.5 ±4.2 mm of Hg and that in case of mitral valve was 23.4±3.7 mm of Hg. Duration of thrombolytic therapy was individualized. Average total dose of streptokinase per patient was 25,25000 ± 8,69350 U (ranging from 20,00000 to 50,00000 U) with majority (28/40) had received a total 20,00000U of streptokinase. Patients were re-evaluated after thrombolysis with clinical, echocardiographic, and cine-uoroscopic evaluation. Total complications (both major and minor bleeding) occurred in 8 patients. Most of them were minor like injection site hematoma, gum bleeding transient GI bleed (hematemesis), hemoptysis and those were resolved spontaneously with conservative management/observational care. Thrombolysis was unsuccessful in 2 patients and death due to massive hemorrhagic CVA occurred in 2 patients. Overall success rate was 90% (36/40). In conclusion, the present study demonstrates the feasibility of thrombolytic therapy for left-sided prosthetic valve occlusion.

Streptokinase irrigation through a percutaneous catheter helps decrease the need for necrosectomy and reduces mortality in necrotizing pancreatitis as part of a step-up approach

BackgroundPercutaneous catheter drainage in pancreatic necrosis with a predominant solid component has a reduced success rate. To improve the efficacy of percutaneous catheter drainage, we used streptokinase in the irrigation fluid in the present study. MethodsIn this retrospective analysis of 4 prospective randomized studies performed at our center from 2014 to 2019, 108 patients were evaluated. We assessed the safety, feasibility, and efficacy of streptokinase irrigation compared to saline irrigation. Data were also analyzed between 50,000 IU and 150,000 IU streptokinase. ResultsThere were 53 patients in the streptokinase irrigation group and 55 in the saline irrigation group, and both groups were comparable in terms of age, sex, etiology, APACHE II score, and percutaneous catheter drainage characteristics. The modified computerised tomography severity index and modified Marshall score at the onset of pain were significantly higher in the streptokinase group. Sepsis reversal was significantly higher in the streptokinase group (75% vs 36%), and the need for necrosectomy (34% vs 54%) was also lower in the streptokinase group. Mortality was lower in the streptokinase group than in the saline group (32% vs 40%). The incidence of bleeding in the streptokinase group was lower than that in the saline group (7% vs 18%). A higher dose of streptokinase (150,000 IU) resulted in lower rates of necrosectomy, bleeding, and mortality compared to those with 50,000 IU streptokinase. ConclusionSignificant reductions in the need for surgery and sepsis reversal were noted in the streptokinase group. The results using 150,000 IU streptokinase were superior to those using 50,000 IU streptokinase.

Safety of thrombolytic therapy in patients with prosthetic heart valve thrombosis who have high international normalized ratio levels.

Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication of heart valve replacement. Based on the current guidelines, the treatment of a large number of these patients could be performed through the administration of thrombolytic agents. In the present study, we aim to assess the safety of thrombolytic therapy in patients with PVT who have high international normalized ratio (INR) levels. In this study, we retrospectively analyzed outcomes of thrombolytic therapy in 65 PVT patients with different levels of INR at the time of fibrinolysis at a tertiary cardiac center. Mean age of patients was 51.6 ± 12.47 years. The tricuspid valve was the most common site of prosthetic valve thrombosis (64.6%). The Median (range) of INR was 2.1 (0.9-4.9). The majority of patients (50.8%) achieved a complete response following thrombolytic treatment. There were no cases of intracranial hemorrhage. Other major and minor bleedings occurred in 3 (4.6%) and 10 (15.4%) patients, respectively. No embolic stroke and systemic embolism were observed. We found no significant difference in the frequency of major (P-value = .809) and minor (P-value = .483) bleeding as well as response to thrombolytic therapy (P-value = .658) between patients with different levels of INR. Total administered dose of Streptokinase was also similar in PVT patients with or without major (P-value = .467) and minor (P-value = .221) bleeding complications. We concluded that there was no significant difference between PVT patients presenting with subtherapeutic and high INR levels who received thrombolytic treatments regarding both minor and major bleeding complications as well as response to thrombolysis.

HALF DOSE VS FULL DOSE THROMBOLYSIS IN PROSTHETIC VALVE THROMBOSIS: IN QUEST OF A BETTER TREATMENT

Thrombolysis is a common treatment for prosthetic valve thrombosis in developing countries. There is unmet need for, better cost-effective treatment. We performed an observational study over 4 years at a single centre comparing half dose with the standard dose of streptokinase or urokinase in 122

P743The efficacy and the safety of the action of the complex drug of fibrin-specific streptokinase in arterial thrombosis in vivo

Abstract Introduction The use of streptokinase (SK) in the clinic is limited by the absence of fibrin-specificity, low degree of recovery of the vessel lumen and hemorrhagic manifestations. We have developed a system of local delivery of SK based on fibrin-specific liposomes, which is a complex drug of streptokinase (SKf), containing “free” SK and SK “associated” with liposomes conjugated with monoclonal antibodies FnI-3C (IgG2 class) to fibrin in a ratio of 40%/60% respectively. The purpose of this study was to evaluate the efficacy and the safety of the action of the SKf in different methods of its administration in arterial thrombosis in vivo. Methods Experiments were performed with 60 outbred male dogs weighing 15–18 kg on a 2-hour model thrombus of the femoral arteries. Experimental group (n=30) received SKf, control group (n=30) - native SK. The drugs were administered intravenously (IV) and intraarterially (IA) in the dose of SK 75000 ME. The observation time was 180 minutes. The pharmacokinetic parameters of the SKf and native SK were studied. Ultrasound, morphological and morphometrical methods of the arteries investigations were used. P<0.05 was taken as statistically significant. Results The SKf had better pharmacokinetic parameters than native SK. The duration of the half-life of SKf was significantly longer than that of native SK 24,1 [21,76; 27,53] min vs. 1,83 [1,64; 1,93] min, (p<0.001). The elimination constant of SKf was lower than that of native SK 0,0291 [0,0175; 0,0407] 1/min vs. 0,3867 [0,1679; 0,5135] 1/min, (p<0.001). Differences between pharmacokinetic parameters of SKf and the native SK, and the presence of fibrin-specificity of SKf contributed to increase of its thrombolytic effect. According to the data of the morphological analysis, the lysis of the central part of the thrombus was noted during the action of native SK. At the same time, the release of SKf initially caused the lysis of the central part of the thrombus with the further dissolution of the thrombus at the periphery. The morphometric evaluation of the artery samples showed that SKf leads to a significant increase in the degree of free vascular lumen compared to the native SK in different methods of its administration: IV - 65,25 [62,67; 68,53]% vs. 52,82 [50,60; 55,71]% respectively, p<0.001; IA - (74,27 [70,39; 77,39]% vs. 68,56 [67,36; 70,87]% respectively, p<0.001. The hemorrhagic complications were not revealed for different methods of SKf administration during the observation period. Conclusions The use of SKf with different methods of administration leads to highly efficient and safe fibrinolyc action in arterial thrombosis in vivo.

Sa1356 - Assessing Role of Higher dose of Streptokinase for Improving the Efficacy of Percutaneous Drainage in Pancreatic Necrosis

Sa1356 - Assessing Role of Higher dose of Streptokinase for Improving the Efficacy of Percutaneous Drainage in Pancreatic Necrosis

Limitation of Infarct Size and the Open Artery Hypothesis: A Conversation With Eugene Braunwald, MD.

Eugene Braunwald received an MD from the New York University School of Medicine. He completed an internal medicine residency at Johns Hopkins Hospital and cardiology fellowships at Mount Sinai Hospital, Columbia University, and the National Heart Institute. He served as chief of cardiology and subsequently clinical director of the institute. From 1968 to 1972, he was the founding chair of medicine at the University of California, San Diego. From 1972 to 1996, he served as chair of medicine at the Brigham and Women’s Hospital. In 1975, he was elected to the National Academy of Sciences. He is now the Distinguished Hersey Professor of Medicine at Harvard Medical School and a senior investigator of the TIMI Study Group, which he founded in 1984. Dr Braunwald replies: I became aware of the importance of AMI in 1951 during an elective in cardiology during my senior year at the New York University School of Medicine. At the time, AMI was by far the most common cause of death in adults in the United States. Of the patients who survived to be admitted to hospitals (no one knew how many AMI patients failed to reach hospital emergency departments), about one third died before discharge, either suddenly, presumably from an arrhythmia, or secondary to pump failure. Of the patients who were discharged alive, about one quarter died within a year, most frequently as a consequence of heart failure or recurrent MI. Pathologists had taught that AMI was usually associated with coronary thrombosis. Indeed, during my cardiology elective, Herrick’s classic article describing AMI was required reading. Its title, “Clinical Features of Sudden Obstruction of the Coronary Arteries,” showed how these 2 conditions (coronary occlusion and AMI) were intertwined.1 My direct involvement in the care of several patients who did not survive the acute event left …

Effective Factors in Door-to-Needle Time for Streptokinase Administration in Patients With Acute Myocardial Infarction Admitted to the Emergency Department.

Background:Cardiovascular incidents are a common cause of death around the world. Acute myocardial infarction (AMI) poses high risks for the patient due to plaque rupture or erosion along with a superimposed non-occlusive thrombus; therefore, timely treatment with antithrombotic agents plays a key role in reducing an AMI mortality rate.Objectives:The present study aimed to assess the time interval between the admission of AMI-suspected patients and treatment initiation.Patients and Methods:This cross-sectional study was conducted on 110 patients admitted to the emergency department of Imam Hussein hospital in Tehran, Iran. Data were collected using checklists, completed by the patients’ next of kin or the emergency staff. To analyze the data, student t- test and analysis of variance were used.Results:In this study, 31 female and 79 male subjects were included, respectively. The mean time to receive the first dose of streptokinase was 66.39 minutes (73.74 minutes for females and 63.5 minutes for male patients), varying from 49.92 minutes in the morning to 69.78 minutes in the afternoon and 72.68 minutes during night shifts.Conclusions:The door-to-needle (DTN) time, in a standard setting, is recommended to be less than 30 minutes. According to the results of this study, the DTN time is comparatively two times longer in females and afternoon and night shifts. Different variables including emergency staff, physicians, patients’ characteristics, and environmental/physical factors induced this difference.

Is accelerated idioventricular rhythm a good marker for reperfusion after streptokinase?

BackgroundAccelerated idioventricular rhythm (AIVR) is a common arrhythmia observed in patients with ST segment elevation myocardial infarction (MI). It is not clear how much value AIVR has in predicting successful reperfusion, since there have been conflicting data regarding this in the past. Streptokinase (STK) even today is the commonest thrombolytic agent used in the public health care set-up in India.1 Most data for the use of STK are from the 1990s, which had showed that at best it is effective in only 50% of patients in restoring adequate flow.2 It is probable that with the current dual-antiplatelet loading dose regimen and other newer medications, this figure could be higher. Also, rescue angioplasty for failed thrombolysis is the standard of care now, unlike before. Hence, we need reliable non-invasive markers to judge successful reperfusion in the present era. While ST segment resolution is the standard marker for reperfusion used in thrombolytic trials, in several instances it is not definitive. An additional marker would thus be very useful, especially in such cases. MethodsThis was a prospective observational study carried out at a public teaching hospital. 200 consecutive patients with a diagnosis of acute MI who were given STK within 12h of index pain were included. The STK dose was 1.5 million units, infused over 30min; the ECG was again recorded after 90min of completion of the infusion. Continuous ECG monitoring for the first 24h of ICCU stay was performed and AIVRs during this period were documented. Early AIVR was defined as that occurring within 2h of completing the STK infusion. Echocardiography was performed 24h after presentation. The time course of AIVR was studied vis-a-vis the outcome of thrombolysis. ResultsAIVR was seen in 41% of the patients. Though AIVR was found to have low sensitivity (45%) and specificity (64%) as a predictor of successful thrombolysis, early AIVR was a reliable sign of successful thrombolysis (p<0.05). The sensitivity (45%) of early AIVR was low; however, the specificity (94%) and positive predictive value (94%) were very good. ConclusionAIVR is a common arrhythmia in the setting of STEMI receiving thrombolytic therapy. Early AIVR is more common with successful thrombolysis, with an excellent positive predictive value. Thus, early AIVR can be used as an additive criterion to ST segment resolution as a non-invasive marker of successful thrombolysis with STK.

Pentoxifylline Increases Antiadhesion Effect of Streptokinase on Postoperative Adhesion Formation: Involvement of Fibrinolytic Pathway.

Pentoxifylline reduces peritoneal adhesions and increases peritoneal fibrinolysis in rodents. Furthermore, the activation of the fibrinolytic system by streptokinase leading to degradation of fibrin is effective in the prevention of adhesion formation. We have investigated the effects of pentoxifylline and streptokinase alone and/or coadministration on postoperative intra-abdominal adhesion formation in adult female NMRI mice. Drugs were administered from the day of surgery until 10days after surgery. At relaparotomy 11days after surgery, the abdomen was opened, and the adhesions were graded in a blinded fashion utilizing the classification system described. Oral gavage administration of lower doses of pentoxifylline (3.125, 6.25, and 12.5mg/kg) had no significant effect on postsurgical adhesion formation, while the higher doses of pentoxifylline (25 and 50mg/kg) significantly decreased postsurgical adhesion formation. Moreover, intraperitoneal injection of lower doses of streptokinase (9.375, 18.75, and 37.5unit/kg, i.p.) had no significant effect on postsurgical adhesion formation, while the higher doses of streptokinase (75 and 150unit/kg) significantly decreased postsurgical adhesion formation. In other series of experiments, coadministration of lower doses of pentoxifylline and streptokinase doses, which were ineffective when given alone, significantly decreased postsurgical intra-abdominal adhesion formation compared with streptokinase control group. The results suggest that pentoxifylline may interfere with streptokinase in the reduction of postoperative intra-abdominal adhesion formation by enhancing local fibrinolytic activity.

Treatment of femoral artery thrombosis with streptokinase and heparin after cardiac catheterization

Background:Thrombosis is the most common complication during cardiac catheterization via femoral artery access. Alongside heparinization, fibrinolytic therapy is recommended if there are signs of ischemia in the lower extremity.Objectives:Given the paucity of data in the existing literature on streptokinase (SK) therapy in pediatrics, we designed this study to assess the efficacy of SK in pediatric patients with diagnosed femoral artery thrombosis following cardiac catheterization.Patients and Methods:The study population initially consisted of 1788 pediatric patients who underwent cardiac catheterization via the femoral artery access. Diminished or absent pulses in the lower extremity were detected in 123 patients, 45 of whom (2.5% of 1788) required treatment and were therefore considered for the next stage of study. Treatment was comprised of post-procedural intravenous heparin, either 50 U/kg/Q4h or 10 - 20 U/kg/h continuously. After heparinization for 24 hours, if the pulse of the affected extremity was not palpable, heparin therapy was continued (heparin-treated group, n = 28), and if the symptoms of femoral artery ischemia were persistent, heparin was discontinued and intravenous SK with a loading dose of 2000 U/kg over 20 - 30 minutes was commenced (SK-treated group, n =17).Results:In the presence of pulselessness in the lower extremity, a maintenance dose of SK (1000 U/kg/h, during 1 - 24 hours) was intravenously administered. Regarding the return of the pulses post-therapeutically, normal and weak/absent pulses were detected in seven (25.2%) and 21 (74.8%) of the 28 patients, respectively, in the heparin-treated group (P value < 0.001), whereas normal and weak/absent pulses were detected in 15 (88.2%) and two (11.8%) of the 17 patients, respectively, in the SK-treated group (P value < 0.001).Conclusions:Our findings demonstrated a high success rate and a low complication rate for systemic SK therapy in femoral artery thrombosis after catheterization.

Properties of streptokinase incorporated into polyethylene glycol microcapsules

Thrombolytic therapy by high doses of streptokinase (SK) that are stipulated by its rapid clearance is accompanied by side effects. In this work for the purpose of lifetime prolongation in bloodstream and decrease in side effects SK was included in microcapsules from water-soluble polyethyleneglygol (PEG) using the double emulsification method. By variation of the emulsification conditions, molecular weight of PEG (20 or 40 kDa) and PEG/SK ratio (12 or 8 mg PEG/1000 IU SK) it was obtained four preparations of PEG-microcapsules with high percent of SK inclusion (approximately 90-91%), which has completely preserved its fibrinolytic activity and released from microcapsules with different rates. The time of SK full release from obtained PEG-microcapsules was varied from 45 to 90 min (pH 7.4; 37 degrees C). The comparative in vitro study ofthrombolytic and side effects of free SK and SK*PEG-microcapsules was conducted. It was found that at equal doses (500 IU/mL) the lysis rates of human plasma clots under the action of encapsulated preparations of SK (with the exception of a small lag period) were equal to the lysis rate induced by free SK. Besides, SK*PEG-microcapsules caused a less exhaustion of plasminogen and fibrinogen in plasma than free SK.

The Effects of Ranitidine and Hydrocortisone on the Complications of Femoral Artery Obstruction Treated by Streptokinase Following Cardiac Catheterization in Pediatric Patients with Congenital Heart Diseases

Background:The most important complication following cardiac catheterization required urgent therapeutic management is vessel obstruction and arterial thrombosis. The morbidity following this complication can be decreased by surgery intervention and/or thrombolytic drugs.Objectives:In this study we evaluated the effects of ranitidine and hydrocortisone on pediatric patients with congenital heart diseases who suffered from femoral artery obstruction following cardiac catheterization on decreasing the events after streptokinase administration.Materials and Methods:This semi experimental study was conducted on 47 patients among 600 cases who underwent cardiac catheterization from April 2002 to December 2011.The patients suffered from distal vessel obstruction following cardiac catheterization with no response to surgery intervention, were enrolled and divided in two groups. Streptokinase was administrated in both groups. Patients in group 2 (25 cases), received ranitidine and hydrocortisone before streptokinase administration. In group 1 (22 cases), the loading dose of streptokinase was 2000IU/kg/ in 20-30 minutes/ infusion and thereafter streptokinase was administrated 1000 IU /kg/hour. In group 2, the loading dose was 3000IU/kg in 20-30 minutes /infusion and 1500 IU/kg/hour as maintenance dose. The infusion dose of streptokinase was decreased and then terminated in 2-3 hours by the time arterial pulse was detected by pulse oximetry.Results:There were 13 (59, 1%) male and 9 (40.9%) female patients in group 1. In group 2, there were 15 (60%) male and 10 (40%) female cases (P = 0.949). Patients in both groups were matched well regarding age, body weight, height and the duration of streptokinase infusion (P < 0.05). The incidence of hematoma was higher in group 1 than group 2 (P = 0.032). the patients of Group 1 required more blood transfusion than group 2 because the incidence of bleeding was more in the first group (P = 0.042). 12 patients in group 1 required fresh frozen plasma transfusion versus 4 patients in group 2 (P = 0.049). Local oozing was detected more in group 1 (P = 0.042). Significant bleeding was occurred in 6 cases in group 1; however this event did not occurrin any patients in group 2 (P = 0.007). Although 4 patients in group 1 suffered from anaphylactic shock after streptokinase administration but no patients in group 2 did. (P = 0.041).Conclusions:Based on the results of this study, we concluded that streptokinase was able to remove the vessel thrombosis at the site of cardiac catheterization and ranitidine and hydrocortisone administration before streptokinase may be effective in order to reduce the complications related to thrombolytic drugs; however the experience of the performer is an issue of concern in this matter.

Thrombolysis in the Developing World: Is There a Role for Streptokinase?

Intravenous thrombolysis with tissue plasminogen activator is the only proven acute therapy for ischemic stroke. This therapy has not been translated into clinical practice in the developing world primarily due to economic constraints. Streptokinase, a lower cost alternative thrombolytic agent, is widely available in developing countries where it is utilized to treat patients with acute coronary syndromes. Although this drug has previously been found to be ineffective in ischemic stroke, the lack of benefit may have been related to a number of factors related to trial design rather than the drug itself. Specific features of prior trial designs that may have adversely affected outcomes include a prolonged treatment window, inclusion of patients with established infarction on computed tomography scan, failure to treat excessive arterial pressures, a fixed dose of streptokinase, and concomitant use of antithrombotic medications. Given the lack of therapeutic alternatives in developing countries, a new trial of streptokinase in acute stroke, utilizing stricter inclusion criteria similar to those in more recent thrombolytic studies, appears warranted.

Efficacy and safety of high dose versus low dose streptokinase for treatment of submassive pulmonary embolism

Abstract Pulmonary embolism (PE) remains a major cause of morbidity and mortality in the general population, the established treatment for PE is anticoagulation. It has previously been demonstrated that thrombolytic therapy can be lifesaving in patients with massive PE (haemodynamic instability and right heart failure). However, the use of thrombolytic therapy in patients with submassive PE (haemodynamically stable) remains a controversial topic. Recent clinical studies, however, support evidence that thrombolysis may favorably affect the outcomes in a wider spectrum of high risk PE patients presenting with right ventricular dysfunction (RVD) as evidenced by decreased right ventricular end diastolic diameter (RVEDD), disappearance of paradoxical septal motion (PSM), and tricuspid regurge (TR) as well as decrease in the pulmonary artery pressure. The aim of this study was to evaluate the efficacy and safety of high dose streptokinase (SK) in 1 h versus low dose SK in 24 h in patients with submassive PE and RVD (high risk PE). The study included 60 patients (28 males and 32 females, mean age 45.5 ± 13.6 years) with submassive PE (positive spiral CT chest) and RVD (proved by echocardiography). Those without contraindications to SK were randomly assigned to receive either high dose (group I) or low dose (group II) of SK. Those with contraindication(s) to SK received anticoagulation (group III). Echocardiography was done before and 72 h after treatment. Right ventricular dysfunction (RVEDD, PSM, and TR) and mean pulmonary artery pressure (PAP) improved significantly 72 h after treatment in groups I and II, while a slight improvement in PAP was observed after treatment in group III. No significant difference was noticed between groups I and II regarding the effect of treatment on RVD or PAP. Statistically nonsignificant difference was found between groups I and II regarding the complications of SK, however a slightly higher risk of bleeding was observed in group I (high dose SK). No significant difference was found between the three groups regarding the mortality. These data suggest that SK can rapidly and safely reverse the pulmonary hypertension and RVD in contrast to anticoagulation. Both protocols of SK are equieffective in rapid reversal of RVD and pulmonary hypertension. Both protocols were safe as proved by absence of difference in mortality over anticoagulant group.

The risks and costs of multiple-generic substitution of topiramate

To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Thrombolysis with a combination of small doses of streptokinase and full doses of heparin.

Thrombolysis with a combination of small doses of streptokinase and full doses of heparin.

The significance of anti-streptokinase antibodies.

Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated in vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r = 0.797; P < 0.005). The addition of specific anti-SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r = -0.93; P = 0.02; fibrin plate assay r = -0.98; P < 0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r = -0.95; P < 0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic state when antibody titres are high (such as those seen within 2 years of an initial dose of SK).