Double-blind Randomized Trial Research Articles

The Second Vasovagal Pacemaker Study (VPSII)

The Second Vasovagal Pacemaker Study (VPSII): A double‐blind randomized controlled trial of pacemaker therapy for the prevention of syncope in patients with recurrent severe vasovagal syncope. Three previous small randomized trials have reported that pacemaker therapy is very beneficial for patients with severe recurrent vasovagal syncope. However these trials were not double blind and were thus at risk of bias in assessment of outcomes and of a ‘placebo‐effect’ of surgery. To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope. A double‐blind randomized trial of pacemaker therapy was performed. After implantation of a dual chamber pacemaker, 100 patients from 15 centres were randomized, double blind, to receive dual chamber pacing (DDD) with rate drop response or to have only sensing with no pacing (ODO). Patients were followed for up to 6 months and the primary outcome of the study was time to first recurrence of syncope. Results: Patients were well matched as to baseline characteristics. In the year prior to randomization patients had had a median of 4 episodes of syncope. No patients were lost to follow up. Of the patients randomized to ODO, 22 of 52 (42%) had recurrent syncope within 6 months, compared to 16 of 48 (33%) of the patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval 25%, 52%) for the ODO group and was 31% (95% confidence interval 17%, 43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% confidence interval −33%, 63%, p = 0.14 one‐sided). Lead dislodgement or repositioning occurred in 7 patients, one patient had vein thrombosis and another had pericardial tamponade leading to removal of the pacemaker system. One patient had infection involving the pacemaker generator. Conclusions: This double blind randomized trial does not confirm the results of earlier smaller unblinded randomized trials. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first line therapy for patients with recurrent vasovagal syncope.

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire

Objective In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. Design Double-blind randomized trial. Setting Healthy volunteers in a multicenter research environment. Patient(s) Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. Intervention(s) 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). Main outcome measure(s) Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone–binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. Result(s) Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. Conclusion(s) Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.

ACE Inhibitors vs. Diuretics for Hypertension: Round II

In the recent ALLHAT double-blind randomized trial, U.S. researchers found that a thiazide diuretic (chlorthalidone) was the most effective of several

5000 ppm toothpaste more effective than 1100 ppm in reversing root caries

Design Six-month double-blind randomised trial of 186 adults who each had to least one PRCL. Intervention Verbal and written instructions were given to participants to brush at least once a day with the allocated dentifrice. Toothbrushes and dentifrices were supplied. Outcome measure New lesions were assessed by a single examiner using fixed clinical criteria and an electric caries monitor (ECM). Results After 6 months, significantly more lesions in the 5000 ppm group had reversed (see Table 1). Non-cavitated lesions were more likely to harden. ECM scores in the 5000 ppm group tended to increase during the study. Conclusions The dentifrice containing 5000 ppm fluoride was found to be significantly better at remineralising PRCL than the one containing 1100 ppm fluoride. Acknowledgement This study was supported by a grant from Colgate Palmolive.

Preoperative transcervical analgesia for laparoscopic sterilization with Filshie clips.A double blind randomized trial

Preoperative transcervical analgesia for laparoscopic sterilization with Filshie clips.A double blind randomized trial

Valsartan/Hydrochlorothiazide is Effective in Hypertensive Patients Inadequately Controlled by Valsartan Monotherapy

Objective: This double-blind parallel-group randomized trial compared the efficacy and safety of fixed combination valsartan 160 mg/hydrochlorothiazide 12.5 mg (Val 160/HCTZ 12.5) once daily (o.d.) and Val 160/hydrochlorothiazide 25 mg (Val 160/HCTZ 25) o.d. vs Val 160 o.d. monotherapy in patients with mild-to-moderate essential hypertension not adequately controlled with valsartan monotherapy. Method: A total of 2002 patients whose BP was inadequately controlled with 4 weeks of Val 160 mg o.d. monotherapy were randomized to treatment for 8 weeks with Val 160 (n = 666), Val 160/HCTZ 12.5 (n = 670) or Val 160/HCTZ 25 (n = 666). Results: Active treatment significantly reduced BP in all groups over the 12 weeks of the study (p < 0.001). The greatest reductions were achieved with Val 160/HCTZ 25. Reductions were 10.8, 12.8 and 14.2 mmHg (sitting diastolic blood pressure) and 15.7, 19.4 and 21.8 mmHg (sitting systolic blood pressure), for the Val 160, Val 160/HCTZ 12.5 and Val 160/HCTZ 25 groups, respectively. Responder rates were high in all groups (49%, 62% and 68%). In elderly patients (≥65 years) responder rates of 70% were achieved with Val 160/HCTZ 25. All treatments were well tolerated, in all patient groups. Conclusions: The combination of Val 160 plus HCTZ 12.5 or HCTZ 25 provides effective and well-tolerated treatment in patients inadequately controlled after 4 weeks of monotherapy. In elderly patients a responder rate of 70% was achieved with Val 160/HCTZ 25.

Prevention of Acute Renal Failure in the Critically Ill

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.

Immuno therapy In Recurrent Spontaneous Abortion: Randomized and Non-Randomized Trials

Objective: The present study was conducted to evaluate the efficacy of immunotherapy with husband's lymphocytes in women with recurrent spontaneous abortion (RSA). Methods: A total of 205 women with three or more consecutive abortions were screened for known causes of recurrent spontaneous abortion. Only 105 women were registered for immunotherapy after excluding the women who had one or the other known cause of abortion. 73 women were registered for immunotherapy against husband's lymphocytes. 32 women were registered under double blind randomized trial. These women were negative for antipaternal cytotoxic antibodies against their husband's cells. Success rate of immunotherapy was same in both the groups. Results: Immunotherapy with husband cells in 73 RSA women was carried out in non-randomized trial. Our results show that the success rate was significantly higher (86%) when compared to other groups of the present study i.e. RSA women who declined to enter the trial (33%), dropouts (50%) and antipaternal cytotoxicity negative RSA women (30%). Antipaternal cytotoxic antibodies (APCA) were taken as the measure of immuno-potentiation. Our results indicate that APCA can be taken as a good indicator for selecting patients for immunotherapy and also to measure whether the RSA women is adequately immunized or not. We have also seen the effect of husband's cells in double blind randomized trial group (32 RSA women). The success rate was 85%, which is comparable to non-randomized trial group. Conclusions: Our results indicate the importance of immunotherapy with husband's lymphocytes in RSA women and also show that APCA can be considered as one of the important immuno-potentiating factor.

Carotid sinus nerve blockade during carotid surgery: A randomised controlled trial

Objectives: we investigated whether carotid sinus nerve infiltration with lignocaine reduced blood pressure lability during the first 24 h following carotid endarterectomy (CEA). Design: prospective randomised double-blind controlled trial. Materials: eighty patients undergoing CEA for significant symptomatic stenosis of the internal carotid artery. Methods: after initial dissection, 5ml of 1% lignocaine or normal saline placebo according to randomisation was infiltrated around the carotid sinus nerve. Blood pressure was measured by intra-arterial cannula during surgery and for four hours afterwards every 15 min, then manually, hourly for 18 h. Results: patients having excision of the carotid sinus nerve were grouped separately for analysis: 29 patients had lignocaine, 33 placebo and 17 excision (one early death with incomplete data was excluded). Mean systolic, diastolic and pulse pressures did not differ significantly between the three groups before carotid sinus nerve infiltration. After infiltration, those patients who had carotid sinus nerve excision, had significantly higher systolic [mean (SD) = 155 (16) mmHg] and diastolic [75 (9) mmHg] pressures than those receiving LA [systolic = 136 (15) mmHg, diastolic = 65 (10) mmHg] or placebo [systolic = 136 (19) mmHg, diastolic = 65 (9) mmHg], (p <0.005 ANOVA). Nerve excision also resulted in wider variability of blood pressure as defined by the mean of individual standard deviations (systolic = 25 mmHg, diastolic = 13 mmHg) compared to LA (systolic = 19 mmHg, diastolic = 12 mmHg) or placebo (systolic = 18 mmHg, diastolic = 10 mmHg) (p <0.05 ANOVA). Normotensive patients had significantly lower mean diastolic pressures (p <0.001 ANOVA) and variability (p <0.05) if they received lignocaine although this did not influence pulse pressure. Conclusions: lignocaine injection of the carotid sinus nerve has no benefit in those patients with existing treated hypertension and only marginal effects in normotensives. It is more important to preserve the carotid sinus nerve if possible.

The oncology nurse's role in educating patients on endocrine therapy for metastatic breast cancer--focus on fulvestrant.

Fulvestrant, an estrogen receptor downregulator, is an effective and a safe endocrine option for postmenopausal women with advanced breast cancer who progress or develop recurrent disease on prior endocrine therapy. The recommended dose is 250 mg given as a single 5-mL or 2 concurrent 2.5-mL monthly intramuscular injections. Common adverse events associated with fulvestrant are hot flashes, nausea, and mild injection site reactions. Applying warm or cold compresses to the injection site can minimize injection site reactions. In randomized double-blind clinical trials, the frequency of injection site reactions for fulvestrant are no different from the comparator (anastrozole) arm. Overall, fulvestrant has a safety profile similar to aromatase inhibitors. Advantages of this agent are its effectiveness in tamoxifen-resistant tumors and the lack of agonistic property, creating a favorable side-effect profile. One limitation is that there is no evidence regarding the safety and effectiveness of fulvestrant in premenopausal women. Among endocrine therapies used to treat breast cancer, fulvestrant is unique not only in its mechanism of action but also in its mode of administration. With oral therapies, the patient fills the prescription in a pharmacy and takes the medication home. In contrast, with monthly fulvestrant intramuscular injection, the patient will have increased contact with the nurse. The increased interaction between the patient and the nurse will affect the role of nurses providing patient education and monitoring.

Risperidone versus haloperidol in long-term hospitalized chronic patients in a double blind randomized trial: a post hoc analysis

Background: Patients who remain in hospital for an extended time pose a special therapeutic challenge. Objectives: The goal of this study was to examine whether the acute response of long-term hospitalized schizophrenic patients differs between haloperidol and risperidone based on a post hoc, sub-analysis of data from a large double blind pivotal trial. Method: Data on chronic schizophrenic patients who had been hospitalized for at least 60 days (median 351 days) prior to entering this 8-week randomized double blind controlled trial were examined. This included 75 patients treated with 4 mg of risperidone and 69 treated with 10 mg of haloperidol. Changes in symptoms were assessed with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinical Global Impression (CGI). Data were analyzed using analysis of variance. Results: The analyses revealed that patients receiving risperidone improved significantly more than those treated with haloperidol. Conclusions: Results suggest that the most often prescribed dose of risperidone, 4 mg, might be more effective for long-stay chronic schizophrenic patients than haloperidol 10 mg.

Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial

To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10–20 mg per day) or losartan (50–100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls ( P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169±11/94±8 mmHg (baseline) to 147±14/84±7 mmHg (post-treatment) ( P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.

Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo‐controlled study of effects on coagulation and fibrinolytic factors

Abstract. Gottsäter A, Rendell M, Hulthén UL, Berntorp E, Mattiasson I (University of Lund, University Hospital, Malmö, Sweden). Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo‐controlled study of effects on coagulation and fibrinolytic factors. J Intern Med 2001; 249: 237–246. Objectives. To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor‐1 (PAI‐1), tissue plasminogen activator (tPA) and resistance to activated protein C. Design. Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. Setting. Department of Endocrinology, University Hospital, Malmö, Sweden. Subjects. Fifty‐one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index ≥ 24 kg m−2 participated in part 1 and 46 participated in part 2. Intervention. Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. Measurements. At baseline and after 3 and 12 months. Results. During 0–3 months in the HRT group, FVII increased (P &lt; 0.01), whereas fibrinogen, AT III and total protein S all decreased (P &lt; 0.001 for all). Changes in variables were expressed as Δ‐values. After 3 months Δ‐values differed between groups for fibrinogen (P &lt; 0.05), AT III (P &lt; 0.001), total protein S (P &lt; 0.001), and PAI‐1 (P &lt; 0.001). During 0–12 months, fibrinogen, total protein S, tPA (P &lt; 0.01 for all) and AT III (P &lt; 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P &lt; 0.05) in total protein S after 3 and 12 months, and a decrease (P &lt; 0.01) in FVIII after 12 months. After 12 months Δ‐values differed for fibrinogen (P &lt; 0.05), AT III (P &lt; 0.05) and total protein S (P &lt; 0.001). Conclusions. Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow‐up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.

The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women

To evaluate the effects of a defined formula of Chinese medicinal herbs (CMH) on menopausal symptoms. A double-blind randomised placebo-controlled trial. Between August 1998 and April 1999, 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH (n = 28) or placebo (n = 27) taken twice daily as a beverage. The primary end-point was change in frequency of vasomotor events (hot flushes and night sweats). The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life (MENQOL) Questionnaire. There was a reduction in average weekly frequency of vasomotor events with CMH (-15%; 95% CI, -31% to +1%) and with placebo (-31%; 95% CI, -42% to -21%). The difference between groups favoured the use of placebo; however, this was not significant (P=0.09). Although significant reductions in scores for the various domains of the MENQOL Questionnaire were observed for both CMH and placebo, there were no significant differences between the two treatment groups for any domain. There was evidence for effect modification by previous use of natural therapies for the vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women, or in improving any of the four symptom domains in the MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by prior use of natural therapies. This finding has implications for future studies.

Vaginal oestradiol for the treatment of lower urinary tract symptoms in postmenopausal womena double-blind placebo-controlled study

A prospective randomised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency, urgency and/or urge incontinence recruited from a tertiary referral urogynaecology clinic. After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo. This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract.

Randomized Trial of Contrast Media Utilization in High-Risk PTCA

Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Use of addyzoa tm in management of male infertility — A prospective double blind randomized trial

International Journal of Gynecology & ObstetricsVolume 70, Issue S2 p. B74-B74 Sperm function Use of addyzoatm in management of male infertility — A prospective double blind randomized trial Arun Tewari, Arun TewariSearch for more papers by this authorJ. Malhotra, J. MalhotraSearch for more papers by this authorN. Malhotra, N. MalhotraSearch for more papers by this authorJ. Shah, J. ShahSearch for more papers by this author Arun Tewari, Arun TewariSearch for more papers by this authorJ. Malhotra, J. MalhotraSearch for more papers by this authorN. Malhotra, N. MalhotraSearch for more papers by this authorJ. Shah, J. ShahSearch for more papers by this author First published: 25 September 2010 https://doi.org/10.1016/S0020-7292(00)85144-9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume70, IssueS22000Pages B74-B74 RelatedInformation

Double blind randomized trial of sucralfate vs placebo during radical radiotherapy for head and neck cancers

This study sought to determine whether sucralfate prophylaxis during a course of high dose radiation therapy (RT) for head and neck cancer decreases acute side effects.Patients receiving curative intent RT for advanced head and neck cancers participated in a single institution double-blind randomized trial comparing sucralfate to placebo. Patients were stratified according to fractionation, use of concurrent chemotherapy, Karnofsky performance status (KPS), age, and pretreatment presence of a feeding gastrostomy. Patients were prospectively evaluated during weekly treatment checks, and analyzed with regard to time (measured in terms of dose) until development of the following: weight loss, mucositis, pain, nutritional intake, and need for a treatment break. After completion of RT, time until healing was similarly compared.Fifty-two patients received sucralfate and 50 received placebo. The mean (+/-SD) prescribed dose was 69 +/- 7 Gy. Sixty-nine patients received BID fractionation and 27 received concurrent chemotherapy. No difference was detected in any outcome measure in the direct comparison between the two groups. On multivariate analysis, weight loss >5% or >10% occurred more frequently in patients receiving chemotherapy (p < 0.01 and p = 0.05, respectively). Grade 3 mucositis was more common in patients receiving chemotherapy (p = 0.05) or BID fractionation (p = 0.04) or having a poor KPS (p = 0.02). Interval to healing was not associated with any of the pretreatment- or treatment-related factors. Sucralfate did not result in any additional toxicity.Prophylactic treatment with sucralfate during high-dose head and neck RT did not decrease acute treatment side effects. Other modalities should be investigated.

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial

Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia

Objective: The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates. Study Design: A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use. Results: Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0.82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups. Conclusions: Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks’ gestation. (Am J Obstet Gynecol 1999;180:1283-8.)