68 research outputs found

    The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review

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    Migrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit

    Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

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    Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

    The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review

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    The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110–2,340), migrant type (170–1,192), TB incidence in source country (19–336) and screening setting (220–1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion: Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA

    Optimization of a Low Cost and Broadly Sensitive Genotyping Assay for HIV-1 Drug Resistance Surveillance and Monitoring in Resource-Limited Settings

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    Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX

    Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

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    A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

    Validation of Epidermal AMBRA1 and Loricrin (AMBLor) as a prognostic biomarker for non-ulcerated AJCC stage I/II cutaneous melanoma

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    Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of metastasis. Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. Results: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant ,with a hazard ratio of 3.469 (95% confidence interval 1.403–8.580, P = 0.007) and an overall NPV of 96.5%. Conclusions These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence

    Implementation outcome instruments for use in physical healthcare settings: a systematic review

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    BACKGROUND: Implementation research aims to facilitate the timely and routine implementation and sustainment of evidence-based interventions and services. A glaring gap in this endeavour is the capability of researchers, healthcare practitioners and managers to quantitatively evaluate implementation efforts using psychometrically sound instruments. To encourage and support the use of precise and accurate implementation outcome measures, this systematic review aimed to identify and appraise studies that assess the measurement properties of quantitative implementation outcome instruments used in physical healthcare settings. METHOD: The following data sources were searched from inception to March 2019, with no language restrictions: MEDLINE, EMBASE, PsycINFO, HMIC, CINAHL and the Cochrane library. Studies that evaluated the measurement properties of implementation outcome instruments in physical healthcare settings were eligible for inclusion. Proctor et al.'s taxonomy of implementation outcomes was used to guide the inclusion of implementation outcomes: acceptability, appropriateness, feasibility, adoption, penetration, implementation cost and sustainability. Methodological quality of the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Psychometric quality of the included instruments was assessed using the Contemporary Psychometrics checklist (ConPsy). Usability was determined by number of items per instrument. RESULTS: Fifty-eight publications reporting on the measurement properties of 55 implementation outcome instruments (65 scales) were identified. The majority of instruments assessed acceptability (n = 33), followed by appropriateness (n = 7), adoption (n = 4), feasibility (n = 4), penetration (n = 4) and sustainability (n = 3) of evidence-based practice. The methodological quality of individual scales was low, with few studies rated as 'excellent' for reliability (6/62) and validity (7/63), and both studies that assessed responsiveness rated as 'poor' (2/2). The psychometric quality of the scales was also low, with 12/65 scales scoring 7 or more out of 22, indicating greater psychometric strength. Six scales (6/65) rated as 'excellent' for usability. CONCLUSION: Investigators assessing implementation outcomes quantitatively should select instruments based on their methodological and psychometric quality to promote consistent and comparable implementation evaluations. Rather than developing ad hoc instruments, we encourage further psychometric testing of instruments with promising methodological and psychometric evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 CRD42017065348
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