Effectiveness of tapentadol prolonged release (PR) compared with oxycodone/naloxone PR for the management of severe chronic low back pain with a neuropathic component: a randomized, controlled, open‐label, phase 3b/4sStudy

[Abstract] OBJECTIVE: To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. METHODS: Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). RESULTS: For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). CONCLUSIONS: The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component

Moxibustion for ulcerative colitis: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicine (CAM) is increasingly used for treatment of inflammatory bowel disease (IBD). Acupuncture-type treatments are among the most popular options. Several studies have reported that moxibustion is effective in ulcerative colitis (UC). The objective of this review was to assess the clinical evidence for or against moxibustion as a treatment for UC.</p> <p>Methods</p> <p>We searched the literature using 18 databases from their inception to February 10, 2010, without language restrictions. We included randomized clinical trials (RCTs), in which human patients with UC were treated with moxibustion. Studies were included if they were placebo-controlled or controlled against a drug therapy or no treatment group. The methodological quality of all RCTs was assessed using the Cochrane risk of bias.</p> <p>Results</p> <p>In total, five RCTs were included. All were of low methodological quality. They compared the effects of moxibustion with conventional drug therapy. Three tested moxibustion against sulfasalazine and two against sulfasalazine plus other drugs. A meta-analysis of five RCTs showed favorable effects of moxibustion on the response rate compared to conventional drug therapy (n = 407; risk ratio = 1.24, 95% CI = 1.11 to 1.38; P < 0.0001; heterogeneity: I²= 16%).</p> <p>Conclusions</p> <p>Current evidence is insufficient to show that moxibustion is an effective treatment of UC. Most of included trials had high risk of bias. More rigorous studies seem warranted.</p

Estimating required information size by quantifying diversity in random-effects model meta-analyses

<p>Abstract</p> <p>Background</p> <p>There is increasing awareness that meta-analyses require a sufficiently large information size to detect or reject an anticipated intervention effect. The required information size in a meta-analysis may be calculated from an anticipated <it>a priori </it>intervention effect or from an intervention effect suggested by trials with low-risk of bias.</p> <p>Methods</p> <p>Information size calculations need to consider the total model variance in a meta-analysis to control type I and type II errors. Here, we derive an adjusting factor for the required information size under any random-effects model meta-analysis.</p> <p>Results</p> <p>We devise a measure of diversity (<it>D</it>²) in a meta-analysis, which is the relative variance reduction when the meta-analysis model is changed from a random-effects into a fixed-effect model. <it>D</it>²is the percentage that the between-trial variability constitutes of the sum of the between-trial variability and a sampling error estimate considering the required information size. <it>D</it>²is different from the intuitively obvious adjusting factor based on the common quantification of heterogeneity, the inconsistency (<it>I</it>²), which may underestimate the required information size. Thus, <it>D</it>²and <it>I</it>²are compared and interpreted using several simulations and clinical examples. In addition we show mathematically that diversity is equal to or greater than inconsistency, that is <it>D</it>²≥ <it>I</it>², for all meta-analyses.</p> <p>Conclusion</p> <p>We conclude that <it>D</it>²seems a better alternative than <it>I</it>²to consider model variation in any random-effects meta-analysis despite the choice of the between trial variance estimator that constitutes the model. Furthermore, <it>D</it>²can readily adjust the required information size in any random-effects model meta-analysis.</p

Evaluation of tracheal stenosis: comparison between computed tomography virtual tracheobronchoscopy with multiplanar reformatting, flexible tracheofiberoscopy and intra-operative findings

The aim of the study was to evaluate and compare various helical CT display modes [virtual endoscopy (VE)] and multiplanar reformations (MPR), conventional flexible tracheobronchoscopy (FT) and intra-operative (IO) findings in patients with tracheal stenosis and to analyze the advantage of MPR and VE in diagnosis and treatment planning and in postoperative follow-up. Thirty-seven patients with tracheal stenosis underwent standard neck and chest CT followed by MPR and VE. Results were correlated with the results of FT and IO findings. Thirty-three of the 37 stenoses were correctly graded and measured adequately using VE. Complete correlation among CT, fiberoptic tracheoscopy, and surgery of stenosis grading, stenosis length and length of planned resection segment of the trachea was noted between 33 of 37 patients with tracheal stenosis. Correlation between VE and IO was noted in 35 of 37 patients and between FT and VE was noted in 33 of 37 patients with tracheal stenosis. The sensitivity of VE was 94–97%, specificity was 100% with comparison to IO findings. The sensitivity and accuracy of MPR was 86–89% and specificity was 100% with comparison to FT findings. The results of the study indicate that VE is an excellent, consistent, and objective technique. VE with MPR is very useful in diagnostic evaluation and treatment planning in patients with tracheal stenosis

Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence

<p>Abstract</p> <p>Background</p> <p>The beta-2-Adrenergic receptor (<it>ADRB2</it>) gene on chromosome 5q33.1 is an important immunoregulatory factor. We and others have previously implicated chromosomal region 5q31-33 for contribution to the genetic susceptibility to Graves disease (GD) in East-Asian populations. Two recent studies showed associations between the single nucleotide polymorphism (SNP) rs1042714 in the <it>ADRB2 </it>gene and GD. In this study, we aimed to fully investigate whether the <it>ADRB2 </it>gene conferred susceptibility to GD in Chinese population, and to perform a meta-analysis of association between <it>ADRB2 </it>and GD.</p> <p>Methods</p> <p>Approximately 1 kb upstream the transcription start site and the entire coding regions of the <it>ADRB2 </it>gene were resequenced in 48 Han Chinese individuals to determine the linkage disequilibrium (LD) patterns. Tag SNPs were selected and genotyped in a case-control collection of 1,118 South Han Chinese subjects, which included 428 GD patients and 690 control subjects. A meta-analysis was performed with the data obtained in the present samples and those available from prior studies.</p> <p>Results</p> <p>Fifteen SNPs in the <it>ADRB2 </it>gene were identified by resequencing and one SNP was novel. Ten tag SNPs were investigated further to assess association of <it>ADRB2 </it>in the case-control collection. Neither individual tag SNP nor haplotypes showed association with GD in Han Chinese population (P > 0.05). Our meta-analysis of the <it>ADRB2 </it>SNP rs1042714 measured heterogeneity between the ethnic groups (I²= 53.1%) and no association to GD was observed in the overall three studies with a random effects model (OR = 1.13, 95% CI, 0.95 to 1.36; P = 0.18). However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I²= 5.9%).</p> <p>Conclusion</p> <p>Our study indicated that the <it>ADRB2 </it>gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population. This inconsistency resulted largely from between-ethnicity heterogeneity.</p

Recent evolution of the NF-κB and inflammasome regulating protein POP2 in primates

<p>Abstract</p> <p>Background</p> <p>Pyrin-only protein 2 (POP2) is a small human protein comprised solely of a pyrin domain that inhibits NF-κB p65/RelA and blocks the formation of functional IL-1β processing inflammasomes. Pyrin proteins are abundant in mammals and several, like POP2, have been linked to activation or regulation of inflammatory processes. Because <it>POP2 </it>knockout mice would help probe the biological role of inflammatory regulation, we thus considered whether <it>POP2 </it>is common in the mammalian lineage.</p> <p>Results</p> <p>BLAST searches revealed that <it>POP2 </it>is absent from the available genomes of not only mice and rats, but those of other domestic mammals and New World monkeys as well. <it>POP2 </it>is however present in the genome of the primate species most closely related to humans including <it>Pan troglodytes </it>(chimpanzees), <it>Macaca mulatta </it>(rhesus macaques) and others. Interestingly, chimpanzee POP2 is identical to human POP2 (huPOP2) at both the DNA and protein level. Macaque POP2 (mqPOP2), although highly conserved is not identical to the human sequence; however, both functions of the human protein are retained. Further, <it>POP2 </it>appears to have arisen in the mammalian genome relatively recently (~25 mya) and likely derived from retrogene insertion of <it>NLRP2</it>.</p> <p>Conclusion</p> <p>Our findings support the hypothesis that the NLR loci of mammals, encoding proteins involved in innate and adaptive immunity as well as mammalian development, have been subject to recent and strong selective pressures. Since POP2 is capable of regulating signaling events and processes linked to innate immunity and inflammation, its presence in the genomes of hominids and Old World primates further suggests that additional regulation of these signals is important in these species.</p

Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography

Background: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol. Methods: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis. Results: In women aged 39–75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15–0.28) and it increased to 0.30 (95% CI 0.18–0.42) with deattenuation. In women aged 40–69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2–22.7%), deattenuation increased this to 29.7% (95% CI 17.8–41.5%). Conclusions: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography