26 research outputs found
Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer
Background
Selective cyclooxygenase inhibitors may retard the progression of cancer, but they
have enhanced thrombotic potential. We report on cardiovascular adverse events in
patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer.
Methods
All serious adverse events that were cardiovascular thrombotic events were reviewed
in 2434 patients with stage II or III colorectal cancer participating in a randomized,
placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative
tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated
prematurely owing to worldwide withdrawal of rofecoxib. To examine possible
persistent risks, we examined cardiovascular thrombotic events reported up to 24
months after the trial was closed.
Results
The median duration of active treatment was 7.4 months. The 1167 patients receiving
rofecoxib and the 1160 patients receiving placebo were well matched, with a median
follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months
(27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events,
16 occurred in the rofecoxib group during or within 14 days after the treatment
period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards
model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet
Trialistsâ Collaboration end point (the combined incidence of death from
cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction;
and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative
risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic
events, six in the rofecoxib group, were reported within the 2 years after trial
closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94;
P = 0.24). Four patients in the rofecoxib group and two in the placebo group died
from thrombotic causes during or within 14 days after the treatment period, and
during the follow-up period, one patient in the rofecoxib group and five patients in
the placebo group died from cardiovascular causes.
Conclusions
Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular
events among patients with a median study treatment of 7.4 monthsâ duration.
(Current Controlled Trials number, ISRCTN98278138.
Reanalysis and Simulation Suggest a Phylogenetic Microarray Does Not Accurately Profile Microbial Communities
The second generation (G2) PhyloChip is designed to detect over 8700 bacteria and archaeal and has been used over 50 publications and conference presentations. Many of those publications reveal that the PhyloChip measures of species richness greatly exceed statistical estimates of richness based on other methods. An examination of probes downloaded from Greengenes suggested that the system may have the potential to distort the observed community structure. This may be due to the sharing of probes by taxa; more than 21% of the taxa in that downloaded data have no unique probes. In-silico simulations using these data showed that a population of 64 taxa representing a typical anaerobic subterranean community returned 96 different taxa, including 15 families incorrectly called present and 19 families incorrectly called absent. A study of nasal and oropharyngeal microbial communities by Lemon et al (2010) found some 1325 taxa using the G2 PhyloChip, however, about 950 of these taxa have, in the downloaded data, no unique probes and cannot be definitively called present. Finally, data from Brodie et al (2007), when re-examined, indicate that the abundance of the majority of detected taxa, are highly correlated with one another, suggesting that many probe sets do not act independently. Based on our analyses of downloaded data, we conclude that outputs from the G2 PhyloChip should be treated with some caution, and that the presence of taxa represented solely by non-unique probes be independently verified
Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences
The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & NemĂ©sio 2007; Donegan 2008, 2009; NemĂ©sio 2009aâb; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported
by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on
18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based
researchers who signed it in the short time span from 20 September to 6 October 2016
Reanalysis and simulation suggest the phylogenetic microarray does not accurately profile microbial communities
The second generation (G2) PhyloChip is designed to detect over 8700 bacteria and archaeal and has been used over 50 publications and conference presentations. Many of those publications reveal that the PhyloChip measures of species richness greatly exceed statistical estimates of richness based on other methods. An examination of probes downloaded from Greengenes suggested that the system may have the potential to distort the observed community structure. This may be due to the sharing of probes by taxa; more than 21% of the taxa in that downloaded data have no unique probes. In-silico simulations using these data showed that a population of 64 taxa representing a typical anaerobic subterranean community returned 96 different taxa, including 15 families incorrectly called present and 19 families incorrectly called absent. A study of nasal and oropharyngeal microbial communities by Lemon et al (2010) found some 1325 taxa using the G2 PhyloChip, however, about 950 of these taxa have, in the downloaded data, no unique probes and cannot be definitively called present. Finally, data from Brodie et al (2007), when re-examined, indicate that the abundance of the majority of detected taxa, are highly correlated with one another, suggesting that many probe sets do not act independently. Based on our analyses of downloaded data, we conclude that outputs from the G2 PhyloChip should be treated with some caution, and that the presence of taxa represented solely by non-unique probes be independently verified
VICTOR : a phase III placebo-controlled trial of rofecoxib in colorectal cancer patients following surgical resection
Background: The cyclo-oxygenase-2 inhibitor, rofecoxib (R) was hypothesised to improve survival in cancer patients who had undergone surgery for colorectal cancer (CRC). This trial recruited from April 2002 until September 2004 when R was withdrawn over concerns about its cardiovascular safety (CVS). This report provides preliminary efficacy results. Methods: Recruited patients had undergone Ro resection of a stage II/III CRC and completion of adjuvant therapy (radiotherapy/chemotherapy/both/neither) less than 12 weeks previously. Excluded patients were those with active peptic ulceration, gastro-intestinal bleeding and those receiving long-term NSAID therapy (except low dose aspirin). 7,000 patients were planned to receive 25mg R daily or an identical placebo (P) for 2 or 5 years, with the goal of detecting a reduction in risk of death - hazard ratio (HR) 0.82. After the trial's premature closure, a modified protocol of the post- treatment follow-up phase and revised statistical analysis plan permitted the detection of a reduction (HR=0.75) in risk of death with 87% power, type I error 0.05, with one pre-planned event-driven interim analysis. Overall survival (OS) and disease-free survival (DFS) were both measured from randomisation, with DFS defined as the time to recurrence or death from any cause. Results: 1,167 of 1,217 patients randomised to R and 1,160 0f 1,217 randomised to P received treatment with median durations of 7.4 months and 8.2 months respectively. Median follow-up was 3.0 and 3.1 years in the two arms (R vs P), with 177 vs 191 deaths and 291 vs 316 DFS events. This pre-planned Kaplan-Meier and log- rank analysis demonstrated that the R patients had slightly longer OS than the P patients, HR 0.94 (95% CI 0.77-1.16; p=0.57). Similarly DFS was slightly higher in the R patients, HR 0.91 (95% CI 0.78-1.07; p=0.25). 19 patients in each arm died without recurrence of CRC. Conclusions: In this study of short treatment duration treatment with R is unlikely to result in a substantial improvement in OS but a small protective effect against recurrence is suggested
Two examples of probe sharing between OTUs.
<p>On the left are shown the 56 probes that represent the OTU 6350. Probes shared with OTU 6368 are shown in the red shape, while those shared with OTU 6366 are shown in blue. The intersection of the red and blue shapes shows probes shared by all three OTUs (centre circle). All 14 and 17 probes (100% of the probe sets) for 6368 and 6366, respectively, can be found in the probe set for OTU 6350. On the right is illustrated how the complete 22 probe, probe set for OTU 5451 can be assembled from probes representing other OTUs.</p
Results of the ISPMA analyses for the 64 OTU âsampleâ.
<p>The number of OTUs representing each family is proportional to the font size in this âWordleâ image. The families shown âpre-analysesâ (top) are represented by one (smaller text), or two (larger text) OTUs. After analyses, using a 95% detection threshold, however, some families are âincreasedâ in their OTU numbers by an order of magnitude. Families shown in red in the input sample are not present in the output set, families in green font in the output set are not present in the input sample. The inset table also shows the outputs at 90 and 92% detection thresholds.</p
Reanalysis of some of the Texas Aerosol data by Brodie et al [<b>3</b>].
<p>Observed and expected distribution of correlation coefficients for pairwise comparisons of intensity of detected OTUs within the classes Actinobacteria, Bacilli, Clostridia, Alpha-, Beta- and Gamma- Proteobacteria and the expected distribution of independent probe sets (black).</p