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Results for “Randomized trial”

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At least 631 records · Page 35Linked to original sources

PubMed1994

Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation.

The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.

Acyclovir↗

PubMed2005

Prolonged conservative treatment or 'early' surgery in sciatica caused by a lumbar disc herniation: rationale and design of a randomized trial [ISRCT 26872154].

BACKGROUND: The design of a randomized multicenter trial is presented on the effectiveness of a prolonged conservative treatment strategy compared with surgery in patients with persisting intense sciatica (lumbosacral radicular syndrome). METHODS/DESIGN: Patients presenting themselves to their general practitioner with disabling sciatica lasting less than twelve weeks are referred to the neurology outpatient department of one of the participating hospitals. After confirmation of the diagnosis and surgical indication MRI scanning is performed. If a distinct disc herniation is discerned which in addition covers the clinically expected site the patient is eligible for randomization. Depending on the outcome of the randomization scheme the patient will either be submitted to prolonged conservative care or surgery. Surgery will be carried out according to the guidelines and between six and twelve weeks after onset of complaints. The experimental therapy consists of a prolonged conservative treatment under supervision of the general practitioner, which may be followed by surgical intervention in case of persisting or progressive disability. The main primary outcome measure is the disease specific disability of daily functioning. Other primary outcome measures are perceived recovery and intensity of legpain. Secondary outcome measures encompass severity of complaints, quality of life, medical consumption, absenteeism, costs and preference. The main research question will be answered at 12 months after randomization. The total follow-up period covers two years. DISCUSSION: Evidence is lacking concerning the optimal treatment of lumbar disc induced sciatica. This pragmatic randomized trial, focusses on the 'timing' of intervention, and will contribute to the decision of the general practictioner and neurologist, regarding referral of patients for surgery.

Humans↗

PubMed2003

A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia.

AIMS: The present study aimed to compare the efficacy of levo-alpha-acetylmethadol (LAAM) and methadone, as measured by retention in treatment and heroin use, in a randomized trial conducted under naturalistic conditions. SETTING: This study is the first randomized trial comparing LAAM with methadone in the primary care setting. Participants were recruited through 29 medical practitioners working in specialist and generalist settings in Australia. PARTICIPANTS: Existing methadone maintenance patients, aged 18 years and over and able to give informed consent, were randomized to receive either LAAM or methadone. A total of 93 patients participated. INTERVENTION: After being trained in the use of LAAM, existing methadone prescribers were then able to determine an individually tailored treatment regimen for each patient. The trial was an open-label study. Methadone and LAAM dosing was supervised through local community pharmacies. Participation in ancillary services (e.g. counselling) was optional for all patients. The treatment period for the trial was 12 months. MEASUREMENTS: Baseline, 3-, 6- and 12-month interviews were conducted. Outcome measures were retention in treatment, self-reported heroin use and serious adverse events. FINDINGS: There were no significant differences between LAAM and methadone on retention in treatment, nor heroin use. There was a trend for LAAM patients to have lower heroin use than methadone patients. Of the seven serious adverse events in the LAAM group, three were not drug-related. There were two dosing errors. CONCLUSIONS: This study demonstrates (a) the efficacy of LAAM as a treatment for heroin dependence, and (b) the capacity for LAAM to be effectively delivered in primary care settings by trained general practitioners and pharmacists. The next challenge is to resolve outstanding safety concerns with LAAM.

Adult↗

PubMed1996

A retrospective quality analysis of 102 randomized trials in four leading urological journals from 1984-1989.

The objective of the present study was to analyse critically the quality of the reporting in 102 randomized trials from four leading urological journals from 1984 to 1989 on the basis of an evaluation system we have developed. This comprises 21 principal parameters selected in terms of their significance for the validity of the studies. These parameters were evaluated by two readers independently of each other as to whether they were specified, not specified, could not be evaluated or were not applicable. The study score of each paper resulted from the sum of all specified criteria. In the 102 studies, out of 21 criteria 69.1% and 69.8% (investigators A and B, respectively) were reported; 29.8% and 29.4%, respectively were not reported, 0.4% and 0.1%, respectively, could not be evaluated and 0.7% did not apply. Such important principal parameters as the sample size (6.9% and 7.8%, respectively), statistical power (11.8%), method of randomization (22.5% and 23.5%, respectively), patient blinding (30.4%), investigator blinding (33.3%), loss to follow-up (34.8% and 35.3%, respectively) and rate of discontinuation (36.0% and 37.7%, respectively) were mentioned least often. The study score of all investigations ranged from 20.5 (97.6%) to 9.0 (42.9%) points. Most (60/59% and 62/61%, respectively) attained values between 16 (76.2%) and 13 (61.9%). Accordingly, randomized trials in urological journals show similar deficits to those in internal medicine, surgery and intensive care medicine. A particular problem is that they concern the most important techniques for systematic reduction of inadvertent errors (bias), and thus doubt is cast upon the hardcore of controlled studies. If it is possible for many authors to mention individual criteria completely, this should also apply (and in particular) to the most critical parameters. In our opinion, the 21 criteria selected for an evaluation system constitute a practical compromise between the 3 and 38 criteria alternatively suggested by other authors. Moreover, use of a comprehensive check list should be the precondition for acceptance of papers for publication.

Publishing↗

PubMed1998

Protocol for prospective collaborative overviews of major randomized trials of blood-pressure-lowering treatments. World Health Organization-International Society of Hypertension Blood Pressure Lowering Treatment Trialists' Collaboration.

OBJECTIVE: To conduct prospectively planned overviews (meta-analyses) of the ongoing randomized trials of blood-pressure-lowering drugs. These overviews should provide reliable data about the effects of newer classes of blood-pressure-lowering drugs (such as angiotensin converting enzyme inhibitors and calcium antagonists) on major causes of cardiovascular mortality and morbidity for a variety of patient groups. METHODS: A registry of major ongoing or planned randomized trials (with more than 1000 patient-years of follow-up for each randomized group) of blood-pressure-lowering agents has been established. The principal investigators of each of these studies have been invited to collaborate in the project and to provide, upon completion of the study, a limited data set for inclusion in the overview analyses. The principal comparisons will be of newer versus older classes of blood-pressure-lowering drugs in treating patients with hypertension and of newer blood-pressure-lowering treatments versus untreated or less treated control conditions for a variety of other groups of patients with a high risk of cardiovascular events. Separate analyses will be conducted for the main drug classes and for major subgroups of patients defined by characteristics such as age, gender, blood pressure, diabetes, and history of renal disease, coronary heart disease or cerebrovascular disease. The principal study outcomes are stroke, major coronary heart disease events, heart failure, total cardiovascular deaths, total cardiovascular events and total mortality. RESULTS: In total 36 trials of blood-pressure-lowering treatments potentially eligible for inclusion in this project have been identified and agreement to collaborate has been confirmed by the investigators in 30 trials, with collaboration pending for six recently identified studies. The first round of analyses will be conducted in 1999 and will be based on total cardiovascular events observed among a total of about 64,000 patients, involving about 240,000 patient-years of follow-up. The second round of analyses will be conducted in 2003 on data from at least 195,000 patients and 899,000 patient-years of follow-up. By that time it is estimated that a total of about 8000 strokes, 12,000 coronary heart disease events and 23,000 cardiovascular events in total will have occurred. This should provide good statistical power to detect even modest cause-specific differences in the incidence of the main study outcomes. CONCLUSIONS: The combination of trial results in prospectively planned, systematic overviews both reduces random errors and avoids biases. As a consequence, this project should provide more reliable information about the effects of newer blood-pressure-lowering drugs than would any one study alone. The use of data from individual patients in these overviews will facilitate investigation of the separate effects of various drug regimens in treating members of major patient subgroups.

Antihypertensive Agents↗

PubMed1994

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.

PURPOSE: To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS: One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS: GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION: (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.

Adolescent↗

PubMed2004

NSABP-32: Phase III, randomized trial comparing axillary resection with sentinal lymph node dissection: a description of the trial.

The NSABP-32 trial is a randomized, phase III clinical trial to compare sentinel node (SN) resection to conventional axillary dissection in clinically node-negative breast cancer patients. The primary aims of the trial are to determine if removal of only SNs provides survival and regional control equivalent to those of axillary dissection, while diminishing the magnitude of surgically related side effects. In order to ensure consistency of the outcomes for this trial, a standardized method of SN surgery has been utilized for all cases. A secondary aim of the B32 trial is to evaluate whether patients with "occult" metastases in the SNs have worse survival. Accrual is taking place at 73 institutions in North America, and 217 surgeons are enrolling patients.

Axilla↗

PubMed2004

[Prospective randomized trial of RFA and chemotherapy for unresectable small hepatocellular carcinoma].

OBJECTIVE: To study the clinical safety and effect on local recurrence in unresectable small hepatocellular carcinoma treated by radiofrequency ablation (RFA) with and without chemotherapy through a prospective randomized trial. METHODS: Thirty-eight unresectable small hepatocellular carcinoma patients with diameter </= 3 cm were selected, of which 27 patients have been followed up for 1 year. Through a prospective randomized trial, 12 patients were in the RFA group and 15 patients in the RFA combined with systemic chemotherapy group. RFA was given image-guided. The regimen of systemic chemotherapy: EADM 50 mg on day 1, 3; CDDP 40 mg on day 1, 3 and FUDR 500 mg on day 1, 2, 3. After RFA treatment, liver function, WBC count and complications were observed on day 1, 4, 7; CT scan was performed in 1, 6, 12 months. The safety and local recurrence were analyzed. RESULTS: There was no local recurrence of the tumor in the two groups 1 month after RFA treatment. The 6- and 12-month local recurrence rates were significantly lower in the combined group than that in RFA group alone (P < 0.01). There were no severe complications in the two groups, and nor was there any significant difference in liver function and WBC count. CONCLUSION: RFA combined with systemic chemotherapy is safe, and it can reduce the local recurrence of unresectable small hepatocellular carcinoma </= 3 cm in diameter.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Can randomized trial outcomes for carotid endarterectomy be achieved in community-wide practice?

The benefit of carotid endarterectomy (CEA) is dependent upon achieving procedural outcomes comparable to those observed in randomized trials. We have extensively examined outcomes of the procedure in the community with a complete medical record (hospital chart) review of over 20,000 Medicare patients undergoing CEA in 10 states. In patients with comparable indications, overall risk of stroke or death of 6.9% in our Medicare studies was comparable to the 6.5% combined event rate in the North American Symptomatic Carotid Endarterectomy Trial. In asymptomatic patients, however, the overall Medicare study result of 3.8% was inferior to the benchmark perioperative combined event rate of 1.5% achieved in the Asymptomatic Carotid Atherosclerosis Study. Our data demonstrated that the randomized trial benchmarks could be achieved or even exceeded at a statewide level. Our studies also documented that evidence-based processes that can reduce perioperative stroke and death (eg, perioperative antiplatelet therapy, patching) are underutilized in the community. Overall process and outcomes assessment show considerable room for improvement. All surgeons performing CEA should use a system-based approach to ensure that all evidence-based processes are employed for patients undergoing CEA and should use indication stratification to document their own outcomes for the procedure.

Aged↗

PubMed2004

Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (non-nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial.

PURPOSE: Tumor volume (TV) is one of the main reported factors determining the outcome of treatment in head-and-neck carcinomas. In this study, the prognostic impact of TV was explored in the context of a randomized trial with the patients assigned to receive standard radiotherapy (RT) alone or RT plus platinum compounds (RT alone, RT plus cisplatin, or RT plus carboplatin). METHODS AND MATERIALS: The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied. Taking into account the magnification factor of the scan and CT slice thickness, a computer with specifically designed software calculated the TV in cubic centimeters. RESULTS: The median overall survival for the whole group of patients was 21.6 months (95% confidence interval, 13.0-30.2) and the 3-year survival rate was 40%. The addition of platinum compounds to RT (Groups 2 and 3) significantly improved the survival rate (RT alone vs. RT plus cisplatin, hazard ratio 0.36, p = 0.002; RT alone vs. RT plus carboplatin, hazard ratio 0.53, p = 0.029). In univariate analysis, the most significant parameters for survival were treatment group, total gross tumor volume (TGTV), complete response, nodal GTV, primary GTV, and performance status. In multivariate analysis, treatment group, TGTV, gender, and primary site were independent prognostic factors for survival. A prognostic threshold of 22.8 cm(3) was detected for TGTV. Patients with a TGTV of <22.8 cm(3) were more likely to achieve a complete response and had a median survival of 45.3 months, and those with a TGTV >22.8 cm(3) had a median survival of 12.3 months (log-rank test, p = 0.0102). CONCLUSION: The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3) derived. Our data indicated that locally advanced head-and-neck carcinomas should not be treated by standard (once-daily) RT alone. Tumor size and disease subsite should be taken into account in future randomized trials to increase their statistical power.

Adult↗

PubMedDate not supplied

Exercise and regional bone mineral density in postmenopausal women: a meta-analytic review of randomized trials.

By using the meta-analytic approach, the purpose of this study was to examine the effects of exercise on regional bone mineral density in postmenopausal women. A total of 11 randomized trials yielding 40 outcome measures and a total of 719 subjects (370 exercise, 349 nonexercise) met the criteria for inclusion: (1) randomized trials; (2) exercise as a primary intervention in postmenopausal women; (3) changes in regional bone mineral density reported; (4) comparative nonexercise group included; (5) studies published in English-language journals between January 1975 and December 1995. Across all designs and categories, treatment effect changes in bone density, weighted by sample size, ranged from -17.10 to 17.30% (mean, 0.27%; 95% confidence interval, 0.16-0.37%). When analyzed separately, sample weighted decreases of approximately -0.51 and -0.86% were found for exercise and nonexercise groups, respectively. Larger effects were observed when groups that did not measure bone density specific to the site loaded and groups that received some type of supplementation (calcium or hormone replacement therapy) were deleted from the model (mean change, 0.76%; 95% confidence interval, 0.6-0.93). Both aerobic and strength training enhanced regional bone mineral density (mean change: aerobic, 1.62% and 95% confidence interval, 1.12-2.12; strength, 0.65% and 95% confidence interval, 0.48-0.83). In conclusion, meta-analytic review of included studies suggests that exercise may slow the rate of bone loss in postmenopausal women. However, it is premature to form strong conclusions regarding the effects of exercise on regional bone mineral density in postmenopausal women. A need exists for additional, well designed studies on this topic before a recommendation can be made regarding the efficacy of exercise as a nonpharmacologic therapy for maintaining and/or increasing regional bone mineral density in postmenopausal women.

Absorptiometry, Photon↗

PubMed2004

Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases.

PURPOSE: Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classes I and II for patients with brain metastases is derived from a database made up primarily of patients with unresected and multiple metastases. An analysis of a previously published randomized trial was performed to determine the applicability of these RPA prognostic classes in the setting of resection of single metastases to the brain. PATIENTS AND METHODS: Ninety-five patients with single metastases to the brain that were treated with complete surgical resection entered this study. Patients were randomly assigned to treatment with postoperative whole brain radiotherapy (WBRT) (n = 49 patients) or no further brain treatment (n = 46 patients). All patients entered on this study had a Karnofsky performance status of > or =70. Therefore, although the RTOG RPA has 3 classes, only patients with RPA classes I (n = 26) or II (n = 69) were eligible for this study analysis. RESULTS: For RPA class I, the median survival was 10.9 months versus 9.8 months for class II patients (P = 0.45). Multivariate analysis showed that only postoperative WBRT, independent of RPA class I or II, lessened the risk of brain tumor recurrence (P < 0.0001). CONCLUSION: This analysis of a randomized trial evaluating postoperative WBRT in the treatment of single metastases to the brain showed no difference in survival between RPA class I or II patients. In addition, the use of postoperative WBRT after complete surgical resection of single brain metastases results in substantially better control of disease in the brain independent of RPA classes I or II.

Adult↗

PubMed2006

Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy.

OBJECTIVE: The objective of this randomized trial was to compare three different steroid regimens in treating type 1 reactions in leprosy in routine clinical practice. DESIGN: The study design was a multicentre, double-blind, randomized, controlled, parallel group trial in patients with acute reversal reactions. The trial was conducted in six leprosy treatment centres in India. A total of 334 participants with acute type 1 reaction were recruited to the trial and randomized to one of three prednisolone regimens: high dose (60 mg per day) or low dose (30 mg per day) both tapered over 20 weeks, and short duration (60 mg per day tapered over 12 weeks). The main outcome measure was the proportion of patients failing to respond to treatment and requiring additional steroids. RESULTS: At the end of 12 months, 46% on the short course required additional steroids compared with 31% on the low dose and 24% on the high dose regimen. CONCLUSIONS: The two 20-week regimens were significantly better than the 12-week regimen. The high dose 20-week regimen was marginally and non-significantly better than the low dose regimen, but the high dose regimen contained 50% more steroid. Reactions in leprosy persist over many months and require long courses of steroids.

Adult↗

PubMed2000

Survival of hip replacements. A comparison of a randomized trial and a registry.

At the authors' hospital, 410 primary total hip replacements were performed on 372 patients between September 1, 1985, and May 31, 1989. All hips were assigned randomly to receive a Charnley prosthesis with an ogee flanged cup or a Spectron prosthesis with a metal backed cup. Eleven-year survivor analysis, using revision as the end point definition of failure, revealed a survival rate of 93.2% +/- 5.8% for the Charnley replacement and 95.9% +/- 3.0% for the Spectron. If each component of the systems was analyzed (concerning aseptic loosening), the ogee cup and the Spectron stem had 100% survival. The survivorship for all 410 hips was 94.5% +/- 3.4%. If the end point definition of failure was expanded to include patient dissatisfaction, the survival rate decreased to 86.3% +/- 4.9%. These survival rates were compared with the rates obtained by the Swedish National Hip Registry. The national cohort included all patients in Sweden who were treated surgically with a Charnley (14,053 patients) or Spectron (metal backed cup) prosthesis (726 patients) between September 1, 1985, and May 31, 1989. Eleven-year survivor analysis revealed a national survival rate of 92.1% +/- 0.7% for the Charnley replacement and 88.6% +/- 6.1% for the Spectron. The analyses from the Swedish Registry are based on more than 160,000 primary operations and 11,500 revisions. Despite the enormous amount of data, there are drawbacks, and registries never can replace the prospective, randomized trial. One reason is the Swedish National Registry is unable to discriminate between the individual cup and stem components when analyzing the cause of revision, and no clinical or radiographic information is collected. A potential drawback for the randomized trial is performance bias because surgeons from specialized centers might perform better than the general orthopaedic surgeon.

Adult↗

PubMed2003

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women.

Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.

Antineoplastic Agents, Hormonal↗

PubMed2001

Low body weight and type of protease inhibitor predict discontinuation and treatment-limiting adverse drug reactions among HIV-infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort.

OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomized trial (RAS, n = 318) and an observational cohort (OBC, n = 505) were used to document reasons for discontinuation and TLADR. Risk factors for discontinuation of the initial PI/developing TLADR were assessed in Cox models. RESULTS: A total of 43 (RAS) and 48% (OBC) discontinued the initial PI therapy within less than 2 years. In both populations TLADR were the most common reason for discontinuation. The incidence of TLADR in RAS was: 8.5 (indinavir), 66.0 (ritonavir), 15.6 (saquinavir hard gel) per 100 person-years of follow-up (P < 0.001). Body weight and type of PI initiated were independent risk factors for treatment discontinuation and TLADR in both groups. In OBC, the risk of developing TLADR increased by 12% per 5 kg lower body weight when starting the PI regimen [the relative hazard (RH) was 1.12 (95% confidence interval: 1.05-1.19) per 5 kg lighter], and starting ritonavir was associated with a three- to sixfold higher risk of TLADR relative to other PI regimens. Very similar results were documented in RAS [RH for body weight was 1.18 (1.07-1.29)]. CONCLUSIONS: Nearly half of the patients stopped treatment with the initial PI, most commonly as a result of adverse drug reactions. Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort.

Adult↗

PubMed1989

Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials.

The use of adrenocorticoids to reduce the morbidity associated with laryngotracheitis (croup) remains controversial despite ten published reports of randomized trials involving 1,286 patients. To determine whether, viewed in aggregate, these studies demonstrate a significant benefit of steroid treatment for this disorder, a meta-analysis of the nine methodologically satisfactory trials was performed. Clinical improvement 12 and 24 hours posttreatment and incidence of endotracheal intubation were evaluated. For each end point, an estimate of the overall effect was obtained by calculating a typical odds ratio and 95% confidence interval. This analysis indicates that the use of steroids in children hospitalized with croup is associated with a significantly increased proportion of patients showing clinical improvement 12 hours (odds ratio = 2.25, 95% confidence interval = 1.66, 3.06) and 24 hours (odds ratio = 3.19, 95% confidence interval = 1.70, 5.99) posttreatment and a significantly reduced incidence of endotracheal intubation (odds ratio = 0.21, 95% confidence interval = 0.05, 0.84). Higher initial doses of steroid (greater than or equal to 125 mg of cortisone or greater than or equal to 100 mg of hydrocortisone) were associated with a larger proportion of patients improved 12 hours posttreatment than was seen with lower doses. These results support the use of steroids in the treatment of hospitalized children with croup and, in the absence of a randomized clinical trial of sufficient size, provide the most reliable estimate of the impact of steroid therapy on the morbidity associated with croup. In addition, the results of this meta-analysis may be used to estimate the number of subjects who would be required to conduct a randomized clinical trial of steroids for the treatment of croup.

Child, Preschool↗

PubMed1994

A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer.

The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high-dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗