Search

Superabsorbent polymers (SAPs) are a promising admixture that can provide internal curing to freshly cast concrete and enhance concrete properties. Although many reviews have explored aspects of SAPs, the links among SAPs' chemical and physical properties, internal curing behaviors, concrete performance, and their large-scale applications are often weakly elucidated. This paper provides an additional review of the chemical structures and physical dimensions of SAPs and their effects on the internal curing kinetic behavior as well as on concrete properties, such as workability, strength, and durability. In addition, different approaches to introducing SAP particles into concrete mixtures are also summarized. Case studies on the use of SAPs in the concrete industry are introduced to provide a better understanding of the greatest potential of SAPs in field applications. The results confirm that the utilization of SAPs in concrete mixtures provides multiple benefits such as improved water curing, reduced shrinkage, and enhanced workability. Selecting the appropriate SAPs is crucial and involves considering factors like absorption rate, durability, and stability. However, achieving uniform distribution of dry SAPs in concrete poses challenges. Further research is required to gain a deeper understanding of the impact of SAPs on transport properties and frost durability. Additionally, the absence of a standard makes it difficult to maintain consistent water-to-cement ratios. These findings provide a theoretical foundation for using SAPs to enhance concrete performance while also highlighting future research directions and challenges. In this article, scientists, engineers, and contractors will find a comprehensive explanation encompassing laboratory investigations, field implementation, and relevant guidance. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA. Methods The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). Results Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients. Conclusion CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients. Trial registration Clinicaltrials.gov, http://clinicaltrials.gov , NCT01500278 [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterised by persistent inflammation of the synovial joints as well as other tissues and organs. Left untreated, it can lead to joint damage, disability and even increased mortality. The disease is driven by inflammatory cytokines that contribute to the chronic inflammation seen in RA. Interleukin-6 (IL-6) is a key pathological cytokine and a target for treatments aiming to alleviate local and systemic inflammation. Despite advances in understanding RA and the introduction of new treatments, achieving sustained remission remains challenging. This review explores the role of IL-6 in RA pathogenesis, its potential as a treatment target and the significance of personalised medicine in RA management. IL-6 has a dual signalling mechanism, classical and trans-signalling, which influences various intracellular pathways. While several targeted therapies have emerged, no single mechanism-based therapy is universally effective due to the diversity and complexity of the disease. Different approaches to targeting IL-6 have been tested, including biologic blockade of receptors or ligands, and inhibition of IL-6 signalling. IL-6 receptor inhibitors have been validated as RA therapeutics, either alone or in combination with other treatments. Tocilizumab, the first approved IL-6 inhibitor, blocks both soluble and membrane-bound IL-6 receptors, reducing the inflammatory cascade. Clinical trials confirm the efficacy and safety of tocilizumab and its role as a treatment option for patients unresponsive to conventional therapies. The benefits of IL-6 inhibition extend beyond reduced joint inflammation to the amelioration of comorbidities like anaemia, cardiovascular disease, depression and osteoporosis. Tailoring treatment to patients' profiles and comorbidities is essential for optimal outcomes. A 'treat-to-profile' approach, focusing on a holistic view of the patient, could improve personalised medicine strategies. Biosimilars – lower-cost alternatives to biologics – further enhance the accessibility and cost-effectiveness of treatment. IL-6 inhibitors present a valuable treatment option for RA management, particularly for patients with specific comorbidities. Plain language summary: What have we learnt from the inhibition of IL-6 in RA and identifying the clinical opportunities for patient outcomes? Rheumatoid arthritis (RA) is a condition where joints become swollen and painful due to long-term (chronic) inflammation. If left untreated, it can cause severe joint damage, disability and even increase the risk of death. The disease is driven by cytokines, which are proteins in the body that help control the immune system and can cause inflammation. One important cytokine is interleukin-6 (IL-6), and scientists are studying ways to block its effects to help people with RA. This review looks at how IL-6 works in RA and how blocking it might help. Despite new treatments, it is still hard to fully control RA. Researchers are trying to find better ways to personalise treatments based on the symptoms of individual patients. One drug called tocilizumab stops IL-6 from working by attaching to its receptor. A receptor is a part of a cell that receives signals from substances like cytokines. When IL-6 attaches to its receptor, it triggers inflammation. Tocilizumab stops IL-6 from attaching to its receptor, reducing pain and inflammation in people with RA. This drug not only helps the joints but may also improve other problems like anaemia, heart disease and even depression that often come with RA. The review suggests that treating RA should involve looking at the person's overall health, not just the joints. IL-6 blockers might be particularly useful for patients with other health issues or for those who have not responded well to other treatments. Biosimilars, which are similar to the original IL-6 blocking drug but less expensive, have expanded the treatment options. Combining personalised treatments with more affordable options could help improve the lives of people with RA. Overall, IL-6 blockers seem to be a promising way to help people with RA, especially when used in a personalised approach that considers the whole person and their overall health. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs or bDMARDs. Methods Data from three completed phase III studies—RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR) and RA-BEACON (bDMARD-IR)—and one completed long-term extension study (RA-BEYOND) were analysed up to 6.5 years [340 weeks (RA-BEAM) and 336 weeks (RA-BUILD and RA-BEACON)]. Low disease activity (LDA) [Simplified Disease Activity Index (SDAI) ≤11], clinical remission (SDAI ≤3.3) and physical function [Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5] were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. Results At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Conclusion Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated. Trial registration United States National Library of Medicine clinical trials database www.clinicaltrials.gov ; RA-BEYOND; NCT01885078. [ABSTRACT FROM AUTHOR]