10,387 research outputs found
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Suture-method versus Through-the-needle Catheters for Continuous Popliteal-sciatic Nerve Blocks: A Randomized Clinical Trial.
BACKGROUND:The basic perineural catheter design has changed minimally since inception, with the catheter introduced through or over a straight needle. The U.S. Food and Drug Administration recently cleared a novel perineural catheter design comprising a catheter attached to the back of a suture-shaped needle that is inserted, advanced along the arc of its curvature pulling the catheter past the target nerve, and then exited through the skin in a second location. The authors hypothesized that analgesia would be noninferior using the new versus traditional catheter design in the first two days after painful foot/ankle surgery with a primary outcome of average pain measured with the Numeric Rating Scale. METHODS:Subjects undergoing painful foot or ankle surgery with a continuous supraparaneural popliteal-sciatic nerve block 5 cm proximal to the bifurcation were randomized to either a suture-type or through-the-needle catheter and subsequent 3-day 0.2% ropivacaine infusion (basal 6 ml/h, bolus 4 ml, lockout 30 min). Subjects received daily follow-up for the first four days after surgery, including assessment for evidence of malfunction or dislodgement of the catheters. RESULTS:During the first two postoperative days the mean ± SD average pain scores were lower in subjects with the suture-catheter (n = 35) compared with the through-the-needle (n = 35) group (2.7 ± 2.4 vs. 3.4 ± 2.4) and found to be statistically noninferior (95% CI, -1.9 to 0.6; P < 0.001). No suture-style catheter was completely dislodged (0%), whereas the tips of three (9%) traditional catheters were found outside of the skin before purposeful removal on postoperative day 3 (P = 0.239). CONCLUSIONS:Suture-type perineural catheters provided noninferior analgesia compared with traditional catheters for continuous popliteal-sciatic blocks after painful foot and ankle surgery. The new catheter design appears to be a viable alternative to traditional designs used for the past seven decades
Duration of adjuvant chemotherapy for stage III colon cancer
BACKGROUND
Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.
METHODS
We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.
RESULTS
After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).
CONCLUSIONS
Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.
Comparison of insulin detemir and insulin glargine in a Basal-Bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: A 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial
Objective: The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type I diabetes mellitus (T1DM).
Methods: This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged >= 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA(1c)) value <= 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA(1c)) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbAlc value <= 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines.
Results: Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m(2); duration of diabetes, 17.2 [11.4] years; HbA(1c), 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA(1c) did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA(1c) were -0.53% and -0.54%. In the 90 patients who completed the trial on once-dally detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA(1c) were-0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA(1c) value <= 7.0% without major hypo-glycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 rnmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events.
Conclusions: During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA(1c)). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia. (Clin Ther. 2009; 31:2086-2097) (C) 2009 Excerpta Medica Inc
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Background
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease
dipyridamole (ASA–ERDP) versus clopidogrel.
Methods
In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive
25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive
75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke.
The secondary outcome was a composite of stroke, myocardial infarction, or death
from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075),
followed by superiority testing, was planned.
Results
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke
occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving
clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The
secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for
ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events
among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365
[3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage
(hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major
hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%],
vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions
The trial did not meet the predefined criteria for noninferiority but showed similar rates
of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either
of the two treatments was superior to the other in the prevention of recurrent
stroke. (ClinicalTrials.gov number, NCT00153062.
Sample size for comparing negative binomial rates in noninferiority and equivalence trials with unequal follow-up times
We derive the sample size formulae for comparing two negative binomial rates
based on both the relative and absolute rate difference metrics in
noninferiority and equivalence trials with unequal follow-up times, and
establish an approximate relationship between the sample sizes required for the
treatment comparison based on the two treatment effect metrics. The proposed
method allows the dispersion parameter to vary by treatment groups. The
accuracy of these methods is assessed by simulations. It is demonstrated that
ignoring the between-subject variation in the follow-up time by setting the
follow-up time for all individuals to be the mean follow-up time may greatly
underestimate the required size, resulting in underpowered studies. Methods are
provided for back-calculating the dispersion parameter based on the published
summary results
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A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.
Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG
Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI
BACKGROUND:
Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR.
METHODS:
We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk.
RESULTS:
At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001).
CONCLUSIONS:
Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .)info:eu-repo/semantics/publishedVersio
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