733 research outputs found
Omalizumab, an Anti-IgE mAb, Receives Approval for the Treatment of Chronic Idiopathic/Spontaneous Urticaria
Omalizumab, an anti-IgE mAb, has recently been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of chronic idiopathic urticaria. Saini et al. (2014) (this issue) report on ASTERIA I, a 40-week randomized, double-blinded, placebo-controlled phase III trial evaluating omalizumab for the treatment of this disease
Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ÎI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-ÎČ and IFN-α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-Îł-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ÎI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate.info:eu-repo/semantics/publishedVersio
Development and validation of an algorithm to accurately identify atopic eczema patients in primary care electronic health records from the UK
Electronic health records hold great promise for clinical and epidemiologic research. Undertaking atopic eczema (AE) research using such data is challenging due to its episodic and heterogeneous nature. We sought to develop and validate a diagnostic algorithm that identifies AE cases based on codes used for electronic records used in the UK Health Improvement Network (THIN). We found that at least one of 5 diagnosis codes plus two treatment codes for any skin-directed therapy were likely to accurately identify patients with AE. To validate this algorithm, a questionnaire was sent to the physicians of 200 randomly selected children and adults. The primary outcome, the positive predictive value (PPV) for a physician-confirmed diagnosis of AE, was 86% (95%CI 80-91%). Additional criteria increased the PPV up to 95% but would miss up to 89% of individuals with physician-confirmed AE. The first and last entered diagnosis codes for individuals showed good agreement with the physician-confirmed age at onset and last disease activity; the mean difference was 0.8 years (95% CI -0.3,1.9) and -1.3 years respectively (95%CI -2.5, -0.1). A combination of diagnostic and prescription codes can be used to reliably estimate the diagnosis and duration of AE from the THIN primary care electronic health records in the UK
Persistence and Effectiveness of Non-Biologic Systemic Therapies for Moderate-Severe Psoriasis in Adults: a Systematic Review
BACKGROUND: The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized. OBJECTIVES: To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ℠3 months. METHODS: MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771. RESULTS: Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ℠75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA. CONCLUSIONS: The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used
What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis?:A systematic review
Randomized controlled pilot trial with ionâexchange water softeners to prevent eczema (SOFTER trial)
Background
Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may prevent eczema. We evaluated the feasibility of a parallel-group assessor-blinded pilot randomized controlled trial to test whether installing a domestic ion-exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy.
Methods
Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion-exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end-points were around feasibility, the primary end-point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end-points were evaluated including frequency of parent-reported doctor-diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study.
Results
One hundred and forty-nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end-point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty-six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO3. At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference â15% (95% CI â38, 8.3%), with most assessments (â„96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor-diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference â12% (95% CI â44, 20%).
Conclusion
A randomized controlled trial of water softeners for the prevention of atopic eczema in high-risk infants is feasible and acceptable
Protocol for an outcome assessor-blinded pilot randomised controlled trial of an ion-exchange water softener for the prevention of atopic eczema in neonates, with an embedded mechanistic study : the softened water for eczema prevention (SOFTER) trial
Introduction
Atopic eczema affects 20% of UK children, and environmental factors are important in its aetiology. Several observational studies suggest an increased risk of atopic eczema in children living in hard water areas. The Softened Water for Eczema Prevention pilot trial tests the feasibility of installing domestic ion-exchange water softeners around the time of birth to reduce the risk of atopic eczema in children with a family history of atopy. A further aim is to explore the pathophysiological mechanisms for this in an embedded mechanistic study.
Methods and analysis
Multicentre parallel group assessor-blinded randomised controlled pilot trial. Participants are newborn babies (n=80) living in a hard water (>250âmg/L calcium carbonate) area at risk of developing atopic eczema because of a family history of atopy. Participants will be randomised prior to birth in a 1:1 ratio. The intervention group will have an ion-exchange water softener installed prior to birth. The control group will receive their usual domestic hard water supply. Follow-up will be until 6âmonths of age. Data will be collected at birth (baseline), 1, 3 and 6 months of age. The main outcome is the proportion of eligible families screened who are willing and able to be randomised. Several secondary feasibility and clinical endpoints will also be evaluated, alongside mechanistic outcomes. Data will be analysed on an intention-to-treat basis. There will be no hypothesis testing for the clinical outcomes. Study acceptability will be evaluated through semistructured interviews.
Ethics and dissemination
This study has been reviewed and given a favourable opinion by the North WestâLiverpool East Research Ethics Committee (Ref: 17/NW/0661). The results of the study will be reported at international conferences and in peer-reviewed scientific journals. We will send participating families a summary of the pilot trial results
Biodiesel production from used cooking oil using a novel surface functionalised TiO2 nano-catalyst
A novel, efficient and recyclable mesoporous TiO2/PrSO3H solid acid nano-catalyst was synthesised by the post-synthetic grafting of propyl sulfonic acid groups onto a mixed phase of a TiO2 support. The synthesised nano-catalyst was characterised using FTIR, SEM, TEM, XPS, N2 adsorptionâdesorption isotherms, XRD, DSC, TGA, and CHNS analysis. The percentage of loading for propyl sulfonic acid on the TiO2 support was calculated using CHNS analysis and TGA. The catalytic performance of TiO2/PrSO3H on the production of the fatty acid methyl esters (FAME) via simultaneous esterification and transesterification reactions from used cooking oil (UCO) has been studied. The effects of different process parameters showed that 98.3% of FAME can be obtained after 9 hrs of reaction time with 1:15 molar ratio of oil to methanol, 60 °C reaction temperature and 4.5 wt% catalyst loading. It was also found that the one-pot post-surface functionalisation strategy with hydrophilic functional groups (-SO3H) enhanced the acid strengths of the nano-catalyst providing more acid sites for the reactants, and improving the accessibility of methanol to the triglycerides (TG)/free fatty acids (FFAs) by increasing the pore volumes/sizes of the nano-catalyst. The solid acid nano-catalyst was re-used in four consecutive runs without significant loss of catalytic efficiency. Finally, the synthesised biodiesel fuel satisfied ASTM and EN standards
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