Summary Background Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to ...assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. Methods In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov , numbers NCT01597245 and NCT01646177. Findings Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; effect size 87·4% (97·5% CI 82·9–91·8) vs placebo; 48·1% (41·2–55·0) vs etanercept) and 336 (87·3%; 80·0% (74·4–85·7) vs placebo; 33·9% (27·0–40·7) vs etanercept) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; 75·1% (69·5–80·8) vs placebo; 35·9% (28·2–43·6) vs etanercept) and 325 (84·2%; 76·9% (71·0–82·8) vs placebo; 30·8% (23·7–37·9) vs etanercept) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p<0·0001 vs placebo or etanercept). In the ixekizumab every 2 weeks group, sPGA 0/1 was achieved by 292 (response rate 83·2%; effect size 80·8% (97·5% CI 75·6–86·0) vs placebo; 47·2% (39·9–54·4) vs etanercept) and 310 (80·5%; 73·8% (67·7–79·9) vs placebo; 38·9% (31·7–46·1) vs etanercept) patients; in the ixekizumab every 4 weeks group by 253 (72·9%; 70·5% (64·6–76·5) vs placebo; 36·9% (29·1–44·7) vs etanercept) and 291 (75·4%; 68·7% (62·3–75·0) vs placebo; 33·8% (26·3–41·3) vs etanercept) patients; in the placebo group by four (2·4%) and 13 (6·7%) patients; and in the etanercept group by 129 (36·0%) and 159 (41·6%) patients (all p<0·0001 vs placebo or etanercept). In combined studies, serious adverse events were reported in 14 (1·9%) of 734 patients given ixekizumab every 2 weeks, 14 (1·9%) of 729 given ixekizumab every 4 weeks, seven (1·9%) of 360 given placebo, and 14 (1·9%) of 739 given etanercept; no deaths were noted. Interpretation Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies. These studies show that selectively neutralising interleukin 17A with a high affinity antibody potentially gives patients with psoriasis a new and effective biological therapy option. Funding Eli Lilly and Co.
In this report, we present an acid-sensitive drug delivery vehicle, termed polyketal nanoparticles, which are designed to target therapeutics to the acidic environments of tumors, inflammatory ...tissues, and phagosomes. The polyketal nanoparticles are formulated from poly(1,4-phenyleneacetone dimethylene ketal) (PPADK), a new hydrophobic polymer which contains ketal linkages in its backbone. The polyketal nanoparticles undergo acid-catalyzed hydrolysis into low molecular weight hydrophilic compounds and should therefore release encapsulated therapeutics at an accelerated rate in acidic environments. Importantly, the polyketal nanoparticles do not generate acidic degradation products after hydrolysis, as with polyester-based biomaterials. Dexamethasone-loaded nanoparticles, 200−600 nm in diameter, were fabricated with PPADK via an emulsion procedure using chloroform and water. The hydrolysis half-life of PPADK was measured to be 102 h at pH 7.4 and 35 h at pH 5.0. PPADK was synthesized by a new polymerization strategy based on the acetal exchange reaction. This new delivery system should find numerous applications in the field of drug delivery because of its ease of synthesis and excellent degradation properties.
In this article, we outline several key concepts to help develop your operating room team. This is an evolutionary process with numerous benefits to the team members, surgeon, and most importantly ...the patients. We outline strategies for engaging and preparing your team members so that the operating room runs more efficiently. We also outline the do's and don'ts of building trust amongst team members which is critical to transforming into a high functioning team.
Background:
Adolescent idiopathic scoliosis (AIS) has evidence-based, nonoperative treatments proven to be effective with early diagnosis and prompt treatment. The purpose of this study was to ...identify potential disparities in access to nonoperative treatment for AIS. Specifically, we sought to determine the interaction of socioeconomic factors on a major curve magnitude and recommend treatment at the initial presentation.
Methods:
A retrospective review of AIS patients who underwent surgery at a single tertiary pediatric hospital between January 1, 2013 and December 31, 2018 was conducted. Patients were divided into 2 groups for comparison: patients with public insurance (PUB) and those with private insurance (PRV). Primary variables analyzed were patient race, Area Deprivation Index (ADI), major curve magnitude, and treatment recommendation at the initial presentation. Univariate and multivariate analyses were conducted to identify the predictors of the major curve magnitude at presentation.
Results:
A total of 341 patients met the inclusion criteria; PUB and PRV groups consisted of 182 (53.4%) and 159 (46.6%) children, respectively. Overall, the major curve magnitude at presentation was significantly higher in PUB compared with PRV patients (50.0° vs. 45.1°;
P
=0.004) and higher in Black patients compared to White patients (51.8 vs. 47.0,
P
=0.042). Surgery was recommended for 49.7% of the PUB group and 43.7% of the PRV group. A lesser number of PUB patients had curve magnitudes within the range of brace indications (≤40°) compared to PRV patients (22.5% vs. 35.2%, respectively;
P
=0.010). The odds of having an initial major curve magnitude <40 degrees were 67% lower among Black patients with public insurance compared to Black patients with private insurance (OR=0.33; 95% CI: 0.13–0.83;
P
=0.019).
Conclusion:
This study demonstrated disparity in access to nonoperative treatment for pediatric scoliosis. Black patients with public insurance were the most at-risk to present with curve magnitudes exceeding brace indications. Future work focused on understanding the reasons for this significant disparity may help to promote more equitable access to effective nonoperative treatment for adolescent idiopathic scoliosis.
Level of Evidence:
III.
The SAGE Handbook of Historical Geography provides an international and in-depth overview of the field with chapters that examine the history, present condition and future significance of historical ...geography in relation to recent developments and current research.
Highly Specific Detection of Oxytocin in Saliva Rana, Muhit; Yildirim, Nimet; Ward, Nancy E ...
International journal of molecular sciences,
03/2023, Letnik:
24, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Oxytocin is a peptide neurophysin hormone made up of nine amino acids and is used in induction of one in four births worldwide (more than 13 percent in the United States). Herein, we have developed ...an antibody alternative aptamer-based electrochemical assay for real-time and point-of-care detection of oxytocin in non-invasive saliva samples. This assay approach is rapid, highly sensitive, specific, and cost-effective. Our aptamer-based electrochemical assay can detect as little as 1 pg/mL of oxytocin in less than 2 min in commercially available pooled saliva samples. Additionally, we did not observe any false positive or false negative signals. This electrochemical assay has the potential to be utilized as a point-of-care monitor for rapid and real-time oxytocin detection in various biological samples such as saliva, blood, and hair extracts.
Minerals and trace elements (MTEs) are micronutrients involved in hundreds of biological processes. Deficiency in MTEs can negatively affect athletic performance. Approximately 50% of athletes have ...reported consuming some form of micronutrient supplement; however, there is limited data confirming their efficacy for improving performance. The aim of this study was to systematically review the role of MTEs in exercise and athletic performance. Six electronic databases and grey literature sources (MEDLINE; EMBASE; CINAHL and SportDISCUS; Web of Science and clinicaltrials.gov) were searched, in accordance with PRISMA guidelines. Results: 17,433 articles were identified and 130 experiments from 128 studies were included. Retrieved articles included Iron (
= 29), Calcium (
= 11), Magnesium, (
= 22), Phosphate (
= 17), Zinc (
= 9), Sodium (
= 15), Boron (
= 4), Selenium (
= 5), Chromium (
= 12) and multi-mineral articles (
= 5). No relevant articles were identified for Copper, Manganese, Iodine, Nickel, Fluoride or Cobalt. Only Iron and Magnesium included articles of sufficient quality to be assigned as 'strong'. Currently, there is little evidence to support the use of MTE supplementation to improve physiological markers of athletic performance, with the possible exception of Iron (in particular, biological situations) and Magnesium as these currently have the strongest quality evidence. Regardless, some MTEs may possess the potential to improve athletic performance, but more high quality research is required before support for these MTEs can be given. PROSPERO preregistered (CRD42018090502).
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