Multicenter Controlled Clinical Trial Research Articles

Introduction of endovascular aneurysm repair into community practice: Initial results with a new Food and Drug Administration-approved device

Purpose: The purpose of this study was to determine the outcome of endovascular aneurysm repair in a defined geographic region during the first 2 years after Food and Drug Administration approval of a new endovascular device. Method: Clinical results of all attempted endovascular aneurysm repairs from 1999 to 2001 with the AneuRx stent graft in the northern California/Nevada region were reviewed. All cases performed in 23 hospitals by 21 endovascular treatment teams were included on an intent-to-treat basis. Community physician training, proctoring, and assistance in case selection was provided by the manufacturer, with outcome monitored by external physician observers and clinical vascular specialists. Results in 22 community hospitals were compared with concurrent results in the regional university hospital training center and with results from the controlled, multicenter AneuRx clinical trial. Results: Endovascular aneurysm repair was attempted in 257 patients by 20 endovascular teams working in 22 community hospitals. The mean number of cases per team was 13 ± 2 (range, 1 to 36). Patient age was 74.1 ± 6.5 years (89% men and 11% women), and 29% of patients were not candidates for open surgical repair because of multiple medical comorbidities. Mean aneurysm diameter was 5.7 ± 0.8 cm. The endoluminal stent graft was successfully deployed in 254 patients (98.8%). In two patients, iliac access could not be obtained, and in one case, the iliac limb was misdeployed and the patient underwent successful open surgical repair. The surgical conversion rate was two of 257 patients (0.8%). The 30-day mortality rate was 1.2%, with one patient dying of stroke, one of multisystem organ failure, and one of cerebral hemorrhage. No device-related deaths occurred. Secondary procedures were performed in 8% of patients. Primary graft patency rate was 98%, and secondary graft patency rate was 100%. Concurrent university training center experience with 100 patients with similar characteristics and aneurysm size was not statistically different (deployment success rate, 100%; 30-day mortality rate, 0%; surgical conversion rate, 0%; secondary procedure rate, 8%). No aneurysm ruptures and no late surgical conversions have been seen in either the community or university experience, with follow-up periods extending to 2 years. Conclusion: Early results of endovascular aneurysm repair introduced into community practice are favorable. Initial community experience, with clinical support from the manufacturer, does not appear to differ significantly from concurrent results in the university training center or from results reported from the multicenter controlled clinical trial with the same device. (J Vasc Surg 2002;36:226-33.)

Rare site for an intramuscular lipoma

Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403. 22 Bailey CJ. The diabetes prevention program: headline results. Br J Diabetes Vasc Dis 2001; 1: 62–64. 23 Harris MI. Impaired glucose tolerance—prevalence and conversion to NIDDM. Diabetic Med 1996; 13 (suppl): S9–S11. 24 Chen H-S, Shaw C-K, Tseng W-P, Chen H-I, Lee M-L. Prevalence of diabetes mellitus and impaired glucose tolerance in Aborigines and Chinese in eastern Taiwan. Diabetes Res Clin Practice 1997; 38: 199–205. 25 Chiasson J-L, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus: a multicenter controlled clinical trial. Ann Intern Med 1994; 121: 928–35. 26 Heine RJ, Nijpels G, Mooy JM. New data on the rate of progression of impaired glucose tolerance to NIDDM and predicting factors. Diabetic Med 1996; 13 (suppl): S12–S14. ARTICLES

Attitudes of maternal-fetal specialists concerning maternal-fetal surgery

Objective: We examined the attitudes of members of the Society for Maternal-Fetal Medicine regarding the clinical, scientific, ethical, and policy issues in maternal-fetal surgery. Study Design: A 43-question survey was distributed to all members of the Society for Maternal-Fetal Medicine. Two mailings and one electronic mail reminder were sent, each with instructions to submit the survey either via US mail or the Internet. The survey included questions in six categories: physician demographic data, experience with maternal-fetal surgery, views on innovative therapies, scientific validation of currently used and proposed procedures, ethical issues, and future directions in public policy. Results: Of the 1639 United States members sent questionnaires, 943 replied (response rate = 59%). Forty-seven percent had referred patients for open fetal surgery for nonlethal conditions, and 69% believed physicians were obligated to inform patients of this option. Seventy-eight percent believed that innovative therapies should be performed only under institutional review board–approved protocols. Although the majority of respondents believed that certain proposed benefits of open fetal surgery for myelomeningocele could offset the risks, the majority (56%) also indicated that the procedure has not been validated. Fifty-seven percent believed that a moratorium should be imposed on open fetal surgery for nonlethal conditions, such as myelomeningocele, until a multicenter-controlled clinical trial is completed. Conclusions: The use of maternal-fetal surgery for nonlethal conditions is highly controversial. The majority of maternal-fetal specialists we surveyed support further research before such procedures are integrated into clinical practice. (Am J Obstet Gynecol 2001;185:1052-8.)

Cerebrovascular arterial dissection in children and young adults

Dissection of the cervical and intracranial portions of the carotid and vertebrobasilar arteries may occur spontaneously or in association with trauma or other underlying risk factors. Astute recognition allows appropriate diagnostic and therapeutic protocols to be instituted. Dissection of extracranial carotid and vertebral arteries differ from their intracranial counterparts, both in terms of presentation and prognosis. Limited data are available regarding the most effective medical treatment of dissection in children and young adults. Interventional neuroradiology may offer a new approach in difficult cases. A multicenter controlled clinical trial is needed to assess the most effective treatment.

Melatonin Potentially Useful but Safety, Efficacy Remain Uncertain

MELATONIN users are the unwitting subjects in a large-scale uncontrolled experiment, according to specialists in sleep and biological rhythms attending a workshop on melatonin and sleep at the National Institutes of Health (NIH) in Bethesda, Md, in August. The scientists urged the NIH to support a multicenter controlled clinical trial to determine melatonin's efficacy and long-term safety. The widespread use of melatonin, the scientists said, highlights the pervasiveness of sleep disorders and the need for physicians to give more weight to sleep complaints. Although no medical catastrophes are known to be associated with melatonin, until solid evidence is in, they said, physicians should prescribe pharmacological and behavioral treatments of known value for sleep disorders, caution patients against the chronic use of melatonin, and monitor those who do take it. The workshop was sponsored by the Trans-NIH Sleep Research Coordinating Committee and the NIH Office for Dietary Supplements. Its spirited and

Pregnancy outcomes in the Diabetes Control and Complications Trial

OBJECTIVE: Our purpose was to examine the maternal and fetal outcomes of the 180 women with insulin-dependent diabetes mellitus who became pregnant during the Diabetes Control and Complications Trial. STUDY DESIGN: The Diabetes Control and Complications Trial was a multicenter controlled clinical trial that compared intensive with conventional therapy in insulin-dependent diabetes mellitus. Intensive therapy, with the aim of achieving normal glycemic control, was initiated in women originally assigned to conventional therapy who actively sought to become pregnant or who became pregnant. RESULTS: A total of 180 women completed 270 pregnancies between 1983 and 1993, with 191 total live births. The mean glycosylated hemoglobin level was significantly different between the treatment groups at conception (7.4% ± 1.3% in intensive vs 8.1% ± 1.7% in conventional therapy, p = 0.0001) but was similar during gestation (6.6% ± 0.8% and 6.6% ± 1.3%). Nine congenital malformations were identified (4.7%), eight of which occurred in women originally assigned to conventional therapy ( p = 0.06). There were 32 spontaneous abortions, 13.3% in the intensive and 10.4% in the women originally assigned to conventional treatment (not significant). There were no significant differences in outcome between the women with conventional treatment who initiated intensive therapy preconception and those who began it after conception. CONCLUSIONS: Timely institution of intensive therapy is associated with rates of spontaneous abortion and congenital malformation similar to those in the nondiabetic population. (AM J OBSTET GYNECOL 1996;174:1343-53.)

Long-term effect of nadolol or nadolol plus isosorbide-5-mononitrate on renal function and ascites formation in patients with cirrhosis

The association beta-blockers plus nitrates has been reported to impair renal function and renal sodium handling, leading to increased risk of development of ascites, or worsening of a preexisting ascites, or increase in the requirements of diuretic agents. In 81 patients with cirrhosis and esophageal varices, participating in a multicenter controlled clinical trial of prophylaxis of variceal bleeding comparing nadolol (NAD) plus isosorbide-5-mononitrate (I5M) with NAD alone, renal function, presence of ascites, and diuretic requirements were assessed at inclusion and after 6 months of follow-up. No significant variation in s-urea or s-creatinine was observed in either group. Three patients in the nadolol group and two in the NAD plus I5M developed ascites at 6 months ( P = .70), and a need to increase diuretic regimen was observed in four and three patients, respectively ( P = .76). Decrease in heart rate and in mean arterial pressure was similar in the two groups. There was a significant correlation between increase in s-creatinine and decrease in mean arterial pressure in the whole series ( P = .015). Only in patients treated with the association was there a significant larger proportion of patients ascitic who became anascitic, than of patients anascitic who became ascitic ( P = .03). In patients treated with the association, there was a significantly larger decrease in hepatic venous pressure gradient ( P = .05). It is concluded that patients treated with the association NAD plus I5M are not at increased risk of developing renal dysfunction or worsening of ascites compared with patients treated with NAD alone. Therefore, the presence of ascites should not be considered a contraindication to the use of this association in patients with cirrhosis and portal hypertension.

Acarbose improved glycemic control in type 2 diabetes

Source Citation Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. A...

Drug Utilization in Very Premature Infants in Neonatal Intensive Care Units

Neonatal drug utilization in very premature infants (gestational age (GA) 24-29 weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 +/- 1.2 (SD) weeks, b.w. 970 +/- 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and analgesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.

Krypton Laser Photocoagulation for Neovascular Lesions of Age-Related Macular Degeneration

The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K.

Krypton Laser Photocoagulation for Neovascular Lesions of Ocular Histoplasmosis

The Ocular Histoplasmosis Study-Krypton Laser is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with ocular histoplasmosis that have either choroidal neovascularization 1 to 199 micron from the center of the foveal avascular zone (FAZ) or choroidal neovascularization 200 micron or further from the FAZ center with blood and pigment extending within 200 micron of the FAZ center. Patients were assigned to photocoagulation (n = 143) or to observation only (n = 145). Recruitment of patients with such lesions has been stopped because more untreated eyes than treated eyes had experienced severe visual acuity loss. At one year after randomization, 24.8% (31/125) of untreated eyes, in contrast with 6.6% (8/121) of treated eyes, had lost six or more lines of visual acuity; by three years after randomization, the corresponding values were 24.6% (15/61) and 4.6% (3/64). The superiority of treatment was evident at every point in time after six months. There were no subgroups in which there was convincing evidence that treatment was harmful. Follow-up of all patients continues to assess long-term results of treatment.

Beneficial effects of S-adenosylmethionine in pregnant women with cholestasis: results of a multicenter controlled clinical trial

Beneficial effects of S-adenosylmethionine in pregnant women with cholestasis: results of a multicenter controlled clinical trial