Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.     

Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries

OBJECTIVES: We assessed the use and effects of acute intravenous and later oral atenolol treatment in a prospectively planned post hoc analysis of the GUSTO-I dataset. BACKGROUND: Early intravenous beta blockade is generally recommended after myocardial infarction, especially for patients with tachycardia and/or hypertension and those without heart failure. METHODS: Besides one of four thrombolytic strategies, patients without hypotension, bradycardia or signs of heart failure were to receive atenolol 5 mg intravenously as soon as possible, another 5 mg intravenously 10 min later and 50 to 100 mg orally daily during hospitalization. We compared the 30-day mortality of patients given no atenolol (n=10,073), any atenolol (n=30,771), any intravenous atenolol (n=18,200), only oral atenolol (n=12,545) and both intravenous and oral drug (n=16,406), after controlling for baseline differences and for early deaths (before oral atenolol could be given). RESULTS: Patients given any atenolol had a lower baseline risk than those not given atenolol. Adjusted 30-day mortality was significantly lower in atenolol-treated patients, but patients treated with intravenous and oral atenolol treatment vs. oral treatment alone were more likely to die (odds ratio, 1.3; 95% confidence interval, 1.0 to 1.5; p=0.02). Subgroups had similar rates of stroke, intracranial hemorrhage and reinfarction, but intravenous atenolol use was associated with more heart failure, shock, recurrent ischemia and pacemaker use than oral atenolol use. CONCLUSIONS: Although atenolol appears to improve outcomes after thrombolysis for myocardial infarction, early intravenous atenolol seems of limited value. The best approach for most patients may be to begin oral atenolol once stable.     

The absence of a procoagulant effect after TNK-t-PA: a comparison with streptokinase and rt-PA

A limitation of current fibrinolytic drugs is the procoagulant activity induced by their administration. TNK is a mutant of tissue plasminogen activator (t-PA) with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and slow plasma clearance, which is administered in a single intravenous bolus. In this study we investigated the procoagulant effect of TNK-t-PA compared to streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40 mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with contraindications to thrombolysis (control group). All patients received a similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn before the start of treatment (time 0) and after 2 hours. Thrombin formation was assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The four patient groups did not differ significantly in age, sex, time to treatment, infarct location, and TAT values at time 0 (mean value +/- standard error of the mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK and controls). In conclusion, our data suggest that, in patients with acute myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions, is devoid of procoagulant effects, evaluated 2 hours after its administration.     

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding

OBJECTIVE: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. METHODS: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. RESULTS: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. CONCLUSION: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.     

Intravenous diltiazem and acute renal failure after cardiac operations

BACKGROUND: Perioperative administration of intravenous diltiazem to patients undergoing cardiac procedures has been shown to decrease the incidence of ischemia and arrhythmias. However, after adopting this practice in our cardiac surgery program, we perceived an increased incidence of postoperative renal dysfunction. METHODS: A directed record review of postoperative renal function was conducted for consecutive patients undergoing cardiac operation for the time periods before and after adoption of prophylactic intravenous diltiazem (0.1 mg.kg-1.h-1 for 24 hours). The two groups were compared using chi 2 and two-sample t tests. The risk of development of postoperative renal failure was modeled with logistic regression. RESULTS: Diltiazem-treated patients (n = 271) were similar to the control patients (n = 143) in terms of age (64 versus 61 years; p = 0.14), ejection fraction (0.46 versus 0.47; p = 0.61), baseline serum creatinine level (1.2 versus 1.1 mg/dL; p = 0.27), prevalence of comorbid conditions, and surgical characteristics. The prevalence of left main coronary artery disease was lower in the diltiazem group than the control group (39% versus 52%; p = 0.01). During the 7-day postoperative period, the average peak serum creatinine level was higher in the diltiazem group (1.7 +/- 0.9 mg/dL; mean +/- 1 standard deviation) than the control group (1.5 +/- 0.5 mg/dL; p = 0.003). The incidence of acute renal failure requiring dialysis was 4.4% in the diltiazem group versus 0.7% in the control group (p = 0.04). There was no difference in length of hospitalization or mortality. The risk of acute renal failure was strongly associated with intravenous diltiazem (adjusted odds ratio [AOR] 6.3; p = 0.08), age (AOR 2.5 per 10 years; p = 0.07), baseline serum creatinine (AOR 4.8 per 1 mg/dL; p = 0.02), the presence of left main coronary disease (AOR 5.3; p = 0.02), and the presence of cerebrovascular disease (AOR 4.5; p = 0.05). CONCLUSIONS: Our retrospective analysis suggests that prophylactic use of intravenous diltiazem in patients undergoing cardiac operations was associated with increased renal dysfunction. Further studies of the risk and benefits of intravenous diltiazem in this setting should be undertaken.     

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Description of a series of 35 patients

Subsequent to the implementation of a severity marker stamp in case notes, an audit was performed in 86 admissions with acute asthma to a specialist centre over a 12 month period. Compared to previous audit the documentation of severity markers was significantly better (PEFR: 52% vs 83% p = 0.001, Respiratory rate: 44% vs 81% p = 0.001, ABG: 72% vs 80% p = 0.04, air entry: 58% vs 86% p = 0.001, speech: 27% vs 86% p = 0.001, exhaustion: 4% vs 86% p = 0.001). In contrast to the previous audit where no patient received FiO2 > 0.35, 66% of the cases in the repeat audit received FiO2 0.60 (p = 0.001). The mean duration of admission was five days and showed highest partial correlation (r = 0.6) to the time in hours for the pulse to fall to 80/min. Multiple linear regression showed that this was the only variable best predicting the duration of admission (R2 = 0.3). Admission pulse rate (p = 0.04) and serum K+ (p = 0.04) best discriminated between patients admitted for over and under five days. Logistic regression identified only the admission pulse as significant in calculating the odds of the patient staying in the hospital for > 5 days.     

Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate analysis of prognostic factors and evaluation of therapeutic modalities]

Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at Keio University Hospital between July 1981 and June 1996 were reviewed retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old, with an average age of 62.7. The primary lesion was located in the lateral wall in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14 (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21 patients (23.1%). The patients were divided into two groups according to the initial main treatment of the primary lesion without regard to chemotherapy: 72 patients (79.1%) who received curative radiotherapy with or without salvage surgery, and 14 patients (15.4%) who underwent curative surgery with or without preoperative and/or postoperative radiation. The remaining 5 patients were treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%) received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by the Kaplan-Meier method as univariate analysis, and compared by the generalized Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five-year survival rates according to stage (UICC classification, 1987) were as follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30 cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p = 0.0274); and (3) location of primary lesion (p = 0.0400). The results of multivariate analysis by Cox's proportional hazards model identified T stage as a significant independent prognostic factor. Evaluation of the therapeutic modalities led to the following conclusions. (1) Differences in the initial treatments of the primary lesion were not reflected in the outcome. (2) Salvage surgery for residual or recurrent tumor contributed to improving the survival. The superior wall type, in particular, seemed to be a good indication for salvage surgery. (3) Although the limitations of radiotherapy are not defined clearly, we have to determine the indications for radical resection of tumors resistant to radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but there were no significant differences in survival between the group that underwent NAC and the other group in any other subset analyses. (5) Among the patients who underwent NAC, the responder (CR + PR) group showed a better five-year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but the difference was not significant.     

Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients

BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.     

Final results of complete hormone blockade versus monotherapy in prostatic metastatic cancer. PSA implications

Of 102 patients with metastatic prostate cancer, 52 were treated with orchidectomy and 50 with CHB; 22 of these received a LHRH analog + Flutamide and 28 orchidectomy + Flutamide. No differences were seen in either arm in terms of age (69.9 vs 70.2 years) or initial PSA (493.3 vs 486.5 ng/ml) variables. After three months treatment, CHB achieved a decrease of PSA higher than monotherapy (52.9 vs 34.5 ng/ml) p<0.01 as well as minimum PSA level during follow-up (41.2 vs 17.5 ng/ml) (p<0.001). Initial clinical response rates were higher in the group treated with complete blockade (42.3% vs 52%) (p=n.s.). Overall, no significant differences were seen between the actuarial curves of biological progression, clinical progression and survival, with expected mean values of 13 vs 12, 14 vs 15 and 34 vs 28 months, respectively. However, when survival was considered as a function of bone disease dissemination, a greater survival rate was seen in patients with minimal M1 disease (p<0.05), and there were no differences between the M2 and M3 arms.     

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.     

Nonsteroidal antiinflammatory drugs are associated with both upper and lower gastrointestinal bleeding

We retrospectively evaluated antiinfective therapy for methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) endocarditis in 54 patients who had 57 treatment courses for the disease. Three treatments were assessed: 27 nafcillin-treated courses of MSSA endocarditis, 18 vancomycin-treated courses of MSSA endocarditis, and 11 vancomycin-treated courses of MRSA endocarditis. At baseline, patients with MSSA treated with vancomycin had more chronic conditions (p<0.01), a lower frequency of intravenous drug use (p<0.01), a lower hematocrit concentration (p<0.05), and a higher serum creatinine concentration (p<0.05) than the nafcillin group. Vancomycin-treated patients had a higher complication rate during therapy (p<0.05) and a longer duration in an intensive care unit (p<0.01) than the nafcillin group. The trend was for a higher complete response rate in the nafcillin group (74% vs 50%, p=0.12), but no difference in mortality (22% vs 28%, p=0.73). Patients with MRSA infection treated with vancomycin had higher mortality than those with MSSA who received that drug (55% vs 28%, p=0.24). Patients with vancomycin-treated MSSA endocarditis may have a poorer outcome than those who receive nafcillin, but this may be influenced by different or more severe clinical features.     

Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation

Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.     

Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral Research Center Group

BACKGROUND: The purpose of this randomized double-blind, placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC classes II, III, and IV.C.2) who had been diagnosed with major depressive disorder (DSM-III-R). METHOD: During a 7-week trial, patients were treated with fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly supportive group psychotherapy. In addition, subjects were rated on the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in the study, 25 were administered fluoxetine and 22 were given placebo. RESULTS: Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment. By endpoint, patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13 (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs. 23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17 score > or = 24). Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally mild and transient. The most frequently noted effects reported by subjects treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in decreasing order of frequency. CONCLUSION: This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression.     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.     

The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia

Sixty-six adults with refractory acute lymphocytic leukemia received salvage therapy with the 'hyper-CVAD' regimen, consisting of eight courses of alternating intensive chemotherapy with growth factor support, followed by oral maintenance chemotherapy. Their outcome was compared with 63 prognostically similar historical control patients treated with high-dose Ara-C plus mitoxantrone with or without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (29 of 66 (44%) vs 24 of 63 (38%)). There were more patients in the current study with primary resistant disease (10 of 66 (15%) vs one of 63 (2%), P = 0.006), and conversely fewer patients with secondary resistance (19 of 66 (29%) vs 28 of 63 (44%), P = 0.06). Recovery of granulocyte counts above 500/microl was significantly faster in the current study when compared to high-dose Ara-C-treated patients who were given GM-CSF (20 vs 25 days, P = 0.04). Survival was prolonged in the hyper-CVAD-treated patients, with most of the benefit seen in first salvage patients (42 vs 20 weeks, P = 0.016). When only first salvage patients were considered, there was a significant difference in disease-free survival in favor of hyper-CVAD (52 vs 20 weeks, P = 0.008). The hyper-CVAD regimen is a more effective and less toxic salvage regimen for relapsed acute lymphocytic leukemia than high-dose Ara-C-based regimens.     

Ineffectiveness of on-site intravenous lines: is prehospital time the culprit?

The purpose of the present study was to test the association between on-site intravenous fluid replacement and mortality in patients with severe trauma. The effect of prehospital time on this association was also evaluated. The design was that of an observational quasi-experimental study comparing 217 patients who had on-site intravenous fluid replacement (IV group) with an equal number of matched patients for whom this intervention was not performed (no-IV group). The patients were individually matched on their Prehospital Index obtained at the scene and were included in the study if they had an on-site Prehospital Index score > 3 and were transported alive to the hospital. The outcome measure of interest was mortality because of injury. The patients in the IV group had a significantly lower mean age (37 vs. 45 years; p < 0.001) and higher incidence of injuries to the head or neck (46 vs. 32%; p = 0.004), chest (34 vs. 17%; p < 0.001), and abdomen (28 vs. 12%; p < 0.001). The IV group also had a higher proportion of patients injured by motor vehicle crashes (41 vs. 27%; p = 0.003), firearms (9 vs. 2%; p = 0.001), and stabbing (20 vs. 9%; p = 0.001). The rate of extremity injuries (38 vs. 59%; p < 0.001) and falls (12 vs. 40%; p < 0.001) was lower for the IV group. In addition, the mean Injury Severity Score was significantly higher for the IV group (15 vs. 9; p < 0.001). The mortality rates for the IV and no-IV groups were 23 and 6% (p < 0.001). Logistic regression analysis showed that after adjusting for patient age, gender, Injury Severity Score, mechanism of injury, and prehospital time, the use of on-site intravenous fluid replacement was associated with a significant increase in the risk of mortality (adjusted odds ratio = 2.3; 95% confidence interval = 1.02-5.28; p = 0.04). To further evaluate the effect of prehospital time on the association between on-site IV use and mortality, the analysis was repeated separately for the following time strata: 0 to 30 minutes, 31 to 60 minutes, and >60 minutes. The adjusted odds ratios (95% confidence interval) for these strata were 1.05 (0.08-14.53; p = 0.97), 3.38 (0.84-13.62; p = 0.08), and 8.40 (1.27-54.69; p = 0.03). These results show that for prehospital times of less than 30 minutes, the use of on-site intravenous fluid replacement provides no benefit, and that for longer times, this intervention is associated with significant increases in the risk of mortality. The results of this observational study have shown that the use of on-site intravenous fluid replacement is associated with an increase in mortality risk and that this association is exacerbated by, but is not solely the result of, increased prehospital times. Our findings are consistent with the hypothesis that early intravenous fluid replacement is harmful because it disrupts the normal physiologic response to severe bleeding. Although this evidence is against the implementation of on-site intravenous fluid replacement for severely injured patients, further studies including randomized controlled trials are required to provide a definitive answer to this question.     

Decision making by elderly patients with cancer and their caregivers

Compared to patients undergoing elective or urgent coronary artery bypass grafting (CABG), those undergoing emergency CABG (EM-CABG) have a higher morbidity and mortality. The use of heparin-bonded circuits (HBC) has been shown to improve clinical outcomes in nonemergent CABG patients. It is not known, however, whether the improved hemostasis and attenuation of the inflammatory response to cardiopulmonary bypass, conferred by HBC, can overcome the high incidence of comorbid risk factors in (EM-CABG) patients and improve their outcomes. A retrospective analysis of 206 consecutive patients undergoing EM-CABG over 4 years (1993-1997) at one institution was performed. Eighty-one patients were treated with conventional non-heparin-bonded circuits (NHBC) with full anticoagulation protocol (FAP, activated clotting time [ACT] > 480 sec); 125 patients were treated with HBC and a lower anticoagulation protocol (LAP, ACT > 280 seconds). Outcomes and results were collected prospectively and are presented as mean +/- SD. Preoperative risk profiles were similar in both treatment groups. Postoperatively, compared with the NHBC group, patients treated with HBC/LAP required fewer homologous donor units (4.1 +/- 10.7 vs 8.2 +/- 13.6 units, p = 0.005), were less likely to require inotropic support (18.6% vs 38.3%, p = 0.005), and had a lower incidence of perioperative myocardial infarction (MI, 3.2% vs 12.3%, p = 0.04) and pulmonary complications (4.0% vs 12.3%, p = 0.04). The use of HBC/LAP resulted in a decreased incidence of postoperative complications (12.8% vs 28.4%, p = 0.01, odds ratio 0.37 with 95% confidence interval [CI] 0.18-0.76). This resulted in a shorter duration of ventilatory support (30.5 +/- 54.0 vs 72.8 +/- 16.7 hours, p = 0.009), ICU stay (38.2 +/- 36.5 vs 91.5 +/- 68.7 hours, p = 0.009), hospital stay (8.0 +/- 7.1 vs 11.0 +/- 8.9 days, p = 0.008), and therefore cost. In conclusion, the use of HBC/LAP in EM-CABG resulted in a reduction of homologous transfusion and postoperative complications associated with decreased hospital stays and cost.     

Comparisons of oral propafenone and sotalol as an initial treatment in patients with symptomatic paroxysmal atrial fibrillation

The main goal of this study is to evaluate the safety and efficacy of propafenone versus sotalol as an initial choice of treatment in patients with symptomatic paroxysmal atrial fibrillation (AF), according to a double-blind randomized system. In the oral propafenone group (n = 41), 2 patients (5%) discontinued therapy because of gastrointestinal discomfort in 1 and dizziness in the other. Thirty-one (79%) of the 39 patients who continued the treatment had effective response to oral propafenone (>75% reduction of symptomatic arrhythmic attacks) on a mean dose of 663 +/- 99 mg/day with a decrease in attack frequency from 10 +/- 3 to 2 +/- 1 times per week. In the oral sotalol group (n = 38), 4 patients (11%) discontinued treatment because of dizziness in 2 and symptomatic bradycardia in 2. Twenty-six of the 34 patients (76%) who continued the treatment had effective response to oral sotalol on a mean dose of 200 +/- 57 mg/day with a decrease in attack frequency from 11 +/- 3 to 2 +/- 1 times per week. Comparisons of the results between propafenone and sotalol groups showed a similar incidence of intolerable (2 of 41 vs 4 of 38, p = 0.42) and tolerable side effects (10 of 39 vs 8 of 34, p = 1.0). The attack frequency at baseline (11 +/- 3 vs 10 +/- 4 times per week, p = 0.23) and after treatment (3 +/- 1 vs 3 +/- 2 times per week, p = 0.85) did not differ significantly between the 2 groups. The incidence of effective response to drugs was also similar (31 of 39 vs 26 of 34, p = 0.78). Furthermore, the decrease of symptom scores (-32 +/- 8% vs -29 +/- 7%, p = 0.18) and percentage decrease of ventricular rate (-15 +/- 4% vs -18 +/- 4%, p = 0.10) during AF were also similar between the 2 groups. In conclusion, oral propafenone and sotalol are equally effective and safe in preventing attacks and alleviating symptoms of paroxysmal AF.     

Update on medical imaging in cancerology]

OBJECTIVE: To compare the rates of phlebitis of peripheral intravenous lines left in place for 72 hours versus rates of those left in place 96 hours. DESIGN: A prospective, nonrandomized study. SETTING: A university teaching hospital with 375 beds. PATIENTS: Consecutive adult patients who received peripheral intravenous lines and were admitted to the wards. MEASUREMENTS: The phlebitis rates were monitored by the i.v. Team for 1 month according to a predetermined definition for phlebitis: palpable cord or at least two of the following: tenderness, warmth, erythema, and induration. RESULTS: A total of 2503 peripheral lines were evaluable. The overall phlebitis rate was 6.8%. The phlebitis rates for lines left in for 72 and 96 hours were not significantly different (3.3% vs 2.6%, p = 1.000) by Fisher's Exact Test and survival analysis. It was estimated that in 1 month approximately 300 intravenous lines potentially could be prolonged beyond 72 hours; 215 lines were changed at 72 hours despite no signs of inflammation, 61 lines were kept till 96 hours, and 19 lines were kept beyond 96 hours. CONCLUSIONS: Phlebitis rate for our peripheral intravenous catheters at 96 hours was not significantly different from that at 72 hours. If intravenous cannulas and lines were prolonged to 96 hours, a potential cost saving of $61,200 per year could be realized.