Vitamin D Deficiency Eradication: A National Priority

Vitamin D Deficiency Eradication: A National Priorit

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Modification of mesoporous silicas

Mesoporous silicas were post-synthetically modified with organometallic complexes in order to produce well defined supported meal centres.The first part of this thesis describes the synthesis of mesoporous silicas MCM-41(A), MCM-41(B) and A1MCM-41 using surfactant templates, MESLC using liquid crystal templates and KMES from an aged gel mixture. The mesoporous materials were characterised by a combination of methods (PXRD, IR spectrometry, MAS NMR, TEM and BET surface area measurements) which resulted in the identification of porous silicas with a hexagonal lattice of pores of 22 - 36 Å and internal surface areas of 848 - 1646 m2g-1. The second part of this thesis describes the post-synthetic modification of mesoporous silicas with the organometallic species trimethylgallium, diethylzinc, Pd(allyl)cp, Pd(CH3CN)2(NO2)Cl and Pd(PPh3)3. MCM-41(A) was modified with trimethylgallium in a direct and indirect vapour phase reaction. MCM-41(B), KMES and MESLC were modified with trimethylgallium via vapour phase reactions. The interaction of trimethylgallium with mesoporous silicas was monitored by EXAFS and led to the loss of one methyl group and surface attachment of diemthylgallium via two silanol groups for MCM-41(A) at 100°C, and MCM-41(B) and KMES at 200°C, and via two silanol groups for MESLC at 200°C. The modification of MCM-41(A), MCM-41(B), KMES and MESLC by diethylzinc resulted in the loss of one ethyl group and interaction of the monoethylzinc species with the silica surface via three silanol groups for MCM-41(A), MCM-41(B) and KMES, and via two silanol groups for MESLC.MCM-41(A), KMES AND MESLC were modified by Pd(allyl)cp leading to the formation of Pd-cp subunits attached to the silica surface via two silanol groups for MCM-41(A) and KMES, and via one silanol group for MESLC. MCM-41(A) was also modified with Pd(CH3CN)2(NO2)Cl leading to the loss of two acetonitrile groups and the anchoring of a Pd(NO2)Cl subunit to the surface of the silica via two silanol groups.</p

Priming with caffeic acid enhances the potential and survival ability of human adipose-derived stem cells to counteract hypoxia

The therapeutic effectiveness of stem cells after transplantation is hampered by the hypoxic milieu of chronic wounds. Prior research has established antioxidant priming as a thorough plan to improve stem cell performance. The purpose of this study was to ascertain how caffeic acid (CA) priming affected the ability of human adipose-derived stem cells (hASCs) to function under hypoxic stress. In order to study the cytoprotective properties of CA, hASCs were primed with CA in CoCl2 hypoxic conditions. Microscopy was used to assess cell morphology, while XTT, Trypan Blue, X-gal, LDH, Live Dead, scratch wound healing, and ROS assays were used to analyze viability, senescence, cell death, proliferation, and reactive oxygen species prevalence in the cells. According to our findings, CA priming enhances hASCs' ability to survive and regenerate in a hypoxic microenvironment more effectively than untreated hASCs. Our in-vitro research suggested that pre-treatment with CA of hASCs could be a unique way to enhance their therapeutic efficacy and ability to survive in hypoxic microenvironments

Childhood Takayasu arteritis: disease course and response to therapy

Abstract Background Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome. Methods A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit. Outcome: disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death. Analysis: logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens. Results Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease (p = 0.02). No additional outcome predictor was identified. Conclusions Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity

Health-related quality of life in children with inflammatory brain disease

Abstract Objective To quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning. Methods This was a multicenter, observational cohort study of children (< 18 years of age) diagnosed with inflammatory brain disease (IBrainD). Patients were included if they had completed at least one Health Related Quality of Life Questionnaire (HRQoL). HRQoL was measured using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL) Generic Core Scales, which provided a total score out of 100. Analyses of trends were performed using linear regression models adjusted for repeated measures over time. Results In this study, 145 patients were included of which 80 (55%) were females. Cognitive dysfunction was the most common presenting symptoms (63%), and small vessel childhood primary angiitis of the CNS was the most common diagnosis (33%). The mean child’s self-reported PedsQL total score at diagnosis was 68.4, and the mean parent’s proxy-reported PedsQL score was 63.4 at diagnosis. Child’s self-reported PedsQL scores reflected poor HRQoL in 52.9% of patients at diagnosis. Seizures or cognitive dysfunction at presentation was associated with statistically significant deficits in HRQoL. Conclusion Pediatric IBrainD is associated with significantly diminished health-related quality of life. Future research should elucidate why these deficits occur and interventions should focus on improving HRQoL in the most affected subdomains, in particular for children presenting with seizures and cognitive dysfunction