The efficacy of systemic glucocorticosteroids for pain in rheumatoid arthritis: a systematic literature review and meta-analysis

Background: Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain.Methods: A systematic literature review of randomised controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences (MDs) were meta-analysed. Heterogeneity (I², tau statistics) and bias (funnel plot, Eggers test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562). Results: 18903 titles, 880 abstracts and 226 full texts were assessed. Thirty three RCTs suitable for the meta-analysis included 2658 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD= -0.65 (15 studies, 95% CI, -0.82, -0.49, p3 to 6 months, and -6mm (95% CI, -10mm, -2mm) at >6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from 5 RCTs suggested improvement also in fatigue during GC treatment.Discussion. Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other than anti-inflammatory GCs should be considered to reduce the long-term burden of pain in RA

Burden of typhoid and paratyphoid fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.)

Influence of Solubilizing Group Removal Rate on the Morphology and Crystallinity of a Diketopyrrolopyrrole-Based Compound

info:eu-repo/semantics/publishe

Impact of thermal annealing on the semicrystalline nanomorphology of spin-coated thin films of regioregular poly(3-alkylthiophene)s as observed by high-resolution transmission electron microscopy and grazing incidence X-ray diffraction

The impact of thermal annealing on the growth of crystalline nanodomains of poly(3-alkylthiophene) (P3AT) in thin films (15–20 nm thick) was investigated as a function of length of alkyl side chain by combined low-dose high-resolution transmission electron microscopy (HR-TEM) and grazing incidence X-ray diffraction (GIXD). Statistical analysis of the data yields the characteristic dimensions of the face-on oriented P3AT nanocrystals, i.e., average stem length l$_c$ along backbones and lateral dimension perpendicular to the stems l$_a$ along side chains. The following trends were identified: (i) in as-spin-coated films, the proportion of face-on oriented nanocrystals increases with the number of carbon atoms in the side chain, (ii) annealing favors the lateral in-plane growth of the nanocrystals along the side chain direction (a$_{P3AT}$ axis), (iii) for a given P3AT, the proportion of face-on oriented domains increases with annealing temperature, (iv) lateral growth along the a$_{P3AT}$ axis is most efficient for the longer octyl side chains, and (v) thermal annealing induces only modest lamellar thickening which is limited by the poor slide diffusion of $\pi$-stacked P3AT chains as opposed to lateral growth favored by weak van der Waals interactions between layers of $\eta$-alkyl side chains. The increase in the population of face-on oriented crystallites, observed when the length of the side chain increases, coincides with a corresponding decrease in the field effect mobility in annealed P3AT thin films

Polymorphism in bulk and thin films : the curious case of dithiophene-DPP(Boc)-dithiophene

Polymorphism is an interesting phenomenon critical to our understanding of structure-property relationships in solid-state functional materials. We report the synthesis and structural characterization of two polymorphic forms of a DPP-Boc derivative, DPP4T-α and DPP4T-β, as well as the study of their optical properties. Thin film studies have been carried out to identify the specific polymorphic form that exists in contact with the substrate and also to obtain a better understanding of the interface morphology with respect to crystal packing. The two polymorphs, DPP4T-α and DPP4T-β, have been structurally characterized using single crystal/powder X-ray diffraction data with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of the type and nature of intermolecular interactions in the supramolecular architectures. DPP4T-α crystallizing in a space group P2/c with Z′ = 0.5 interlinked via C- H···O/π and π···π interactions forms 2D herringbone sheets. In the polymorph DPP4T-β with space group P1 and Z′ = 1, the crystal packing is stabilized by CH···π and π···π interactions forming a columnar network. From considerations of density and from lattice energy calculations, it can be concluded that the α-form is more stable in bulk. In thin films the β-form was found to be more stable. This work gives a unique example where the polymorphism could be identified and separated both in the bulk and in thin films. This study on the structural effects of polymorphism is useful for further development of DPP-based materials and also for targeted design of other functional materials

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)