Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction.</p> <p>Methods</p> <p>One hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle.</p> <p>Results</p> <p>Among 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups.</p> <p>Conclusions</p> <p>Etoricoxib is more effective than celecoxib and placebo for using as preemptive analgesia for acute postoperative pain control in patients underwent arthroscopic anterior cruciate ligament reconstruction.</p> <p>Trial registration number</p> <p>NCT01017380</p

The Predatory Ecology of Deinonychus and the Origin of Flapping in Birds

Most non-avian theropod dinosaurs are characterized by fearsome serrated teeth and sharp recurved claws. Interpretation of theropod predatory ecology is typically based on functional morphological analysis of these and other physical features. The notorious hypertrophied ‘killing claw’ on pedal digit (D) II of the maniraptoran theropod Deinonychus (Paraves: Dromaeosauridae) is hypothesized to have been a predatory adaptation for slashing or climbing, leading to the suggestion that Deinonychus and other dromaeosaurids were cursorial predators specialized for actively attacking and killing prey several times larger than themselves. However, this hypothesis is problematic as extant animals that possess similarly hypertrophied claws do not use them to slash or climb up prey. Here we offer an alternative interpretation: that the hypertrophied D-II claw of dromaeosaurids was functionally analogous to the enlarged talon also found on D-II of extant Accipitridae (hawks and eagles; one family of the birds commonly known as “raptors”). Here, the talon is used to maintain grip on prey of subequal body size to the predator, while the victim is pinned down by the body weight of the raptor and dismembered by the beak. The foot of Deinonychus exhibits morphology consistent with a grasping function, supportive of the prey immobilisation behavior model. Opposite morphological trends within Deinonychosauria (Dromaeosauridae + Troodontidae) are indicative of ecological separation. Placed in context of avian evolution, the grasping foot of Deinonychus and other terrestrial predatory paravians is hypothesized to have been an exaptation for the grasping foot of arboreal perching birds. Here we also describe “stability flapping”, a novel behaviour executed for positioning and stability during the initial stages of prey immobilisation, which may have been pivotal to the evolution of the flapping stroke. These findings overhaul our perception of predatory dinosaurs and highlight the role of exaptation in the evolution of novel structures and behaviours

Palaeoclimate: Lags within the Younger Dryas

A slowing Atlantic overturning circulation during the last deglacial warming caused abrupt cooling in the Northern Hemisphere. Lake sediment records suggest that hydrological change in Europe lagged the temperature drop by almost 200 years.Peer Reviewe

REDUCTION IN THE RATE OF EGFR DECLINE WITH SEMAGLUTIDE VS PLACEBO: A POST HOC POOLED ANALYSIS OF SUSTAIN 6 AND PIONEER 6

Background and Aims The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated that once-weekly (OW) subcutaneous (s.c.) semaglutide may have beneficial effects on kidney function. SUSTAIN 6 and the more recent PIONEER 6 CVOT (oral semaglutide) had similar designs and subject populations; both evaluated the effects of semaglutide compared with placebo on important macro- and microvascular outcomes. This post hoc analysis of pooled data from the two trials evaluated the effects of semaglutide vs placebo on kidney function, assessed by estimated glomerular filtration rate (eGFR) slope. Method Data for 6,480 subjects from SUSTAIN 6 (OW s.c. semaglutide 0.5 and 1.0 mg or placebo, n=3,297; median follow-up 2.1 years) and PIONEER 6 (oral semaglutide once-daily 14 mg or placebo, n=3,183; median follow-up 1.3 years) were pooled into two groups: semaglutide and placebo. Annual change in eGFR was compared between semaglutide and placebo in patients with eGFR data at baseline, both overall and by baseline eGFR subgroup (≥30–\u3c60 or ≥60 mL/min/1.73 m2). Data were analysed using a linear random regression model with individual intercept and time slope. Estimated treatment difference (ETD) between annual rates of eGFR slope (from baseline to timepoint of interest) was calculated at Year 1 and Year 2 (Year 2 data predominantly from SUSTAIN 6); interaction p-values indicated differences between subgroups. Results In the overall treatment population, the annual rate of eGFR change was 0.60 mL/min/1.73 m2 (95% confidence interval [CI]: 0.31;0.90; p\u3c0.0001) lower with semaglutide vs placebo in Year 1. In the subgroup with an eGFR ≥60 mL/min/1.73 m2 at baseline, the ETD for semaglutide vs placebo at Year 1 was 0.48 mL/min/1.73 m2/year (95% CI: 0.13;0.82). Whereas, at Year 1, the subgroup with eGFR ≥30–\u3c60 mL/min/1.73 m2 had an ETD of 1.07 mL/min/1.73 m2/year (95% CI: 0.46;1.68) (Table). Accordingly, a numerically larger difference in ETD was observed in the eGFR ≥30–\u3c60 mL/min/1.73 m2 vs the eGFR ≥60 mL/min/1.73 m2 subgroup (not statistically significant; pinteraction=0.21). Conclusion Semaglutide was associated with a significantly smaller decline in renal function compared with placebo in subjects across stages of impaired kidney function at baseline. Although benefits were observed in the overall population, the findings indicate that the primary benefit may be observed in those with established chronic kidney disease

Effects of Semaglutide on CKD Outcomes: A Post Hoc Pooled Analysis from the SUSTAIN 6 and PIONEER 6 Trials

BACKGROUND The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a benefit on kidney disease with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo (PBO) in subjects with type 2 diabetes (T2D) at high CV risk. The PIONEER 6 CVOT reported CV safety with oral once-daily (OD) semaglutide in a similar cohort. This post hoc analysis evaluated the potential benefit of semaglutide vs PBO on chronic kidney disease (CKD) outcomes. METHODS Data from 6,480 subjects (SUSTAIN 6: N=3,297; median follow-up, 2.1 years; mean baseline [BL] estimated glomerular filtration rate [eGFR], 76 mL/min/1.73 m2; PIONEER 6: N=3,183; median follow-up, 1.3 years; mean BL eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 and 1.0 mg s.c. OW, 14 mg oral OD) or PBO. Time to onset of persistent eGFR reduction (≥30, ≥40, ≥50, ≥57% [corresponding to doubling of serum creatinine]) was evaluated overall and by BL eGFR subgroup (≥30–\u3c60, ≥60 mL/min/1.73 m2). Analyses used a Cox proportional-hazards model with treatment group and eGFR subgroup and interaction between both as fixed factors stratified by trial. RESULTS In the overall population, hazard ratios (HRs) for onset of persistent eGFR reductions with semaglutide vs PBO were not statistically significantly different from 1, but estimated HRs were \u3c1.0, favoring semaglutide. Estimated HRs for semaglutide vs PBO in the eGFR ≥30–\u3c60 mL/min/1.73 m2 subgroup were generally lower than in the overall population; semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs PBO (p=0.03; Figure). No significant interactions between treatment and eGFR subgroup were observed. CONCLUSION This analysis of semaglutide CVOTs supports the possibility of a smaller magnitude of eGFR decline with semaglutide vs PBO and suggests a potential kidney disease benefit of semaglutide vs PBO in people with T2D and established CKD