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- Owolabi, Mayowa O., et al.
(författare)
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Gaps in Guidelines for the Management of Diabetes in Low- and Middle-Income Versus High-Income Countries : A Systematic Review
- 2018
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Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:5, s. 1097-1105
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE The extent to which diabetes (DM) practice guidelines, often based on evidence from high-income countries (HIC), can be implemented to improve outcomes in low-and middle-income countries (LMIC) is a critical challenge. We carried out a systematic review to compare type 2 DM guidelines in individual LMIC versus HIC over the past decade to identify aspects that could be improved to facilitate implementation. RESEARCH DESIGN AND METHODS Eligible guidelines were sought from online databases and websites of diabetes associations and ministries of health. Type 2 DM guidelines published between 2006 and 2016 with accessible full publications were included. Each of the 54 eligible guidelines was assessed for compliance with the Institute of Medicine (IOM) standards, coverage of the cardiovascular quadrangle (epidemiologic surveillance, prevention, acute care, and rehabilitation), translatability, and its target audiences. RESULTS Most LMIC guidelines were inadequate in terms of applicability, clarity, and dissemination plan as well as socioeconomic and ethical-legal contextualization. LMIC guidelines targeted mainly health care providers, with only a few including patients (7%), payers (11%), and policy makers (18%) as their target audiences. Compared with HIC guidelines, the spectrum of DM clinical care addressed by LMIC guidelines was narrow. Most guidelines from the LMIC complied with less than half of the IOM standards, with 12% of the LMIC guidelines satisfying at least four IOM criteria as opposed to 60% of the HIC guidelines (P < 0.001). CONCLUSIONS A new approach to the contextualization, content development, and delivery of LMIC guidelines is needed to improve outcomes.
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| 3. |
- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 6. |
- Horwich, A, et al.
(författare)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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| 9. |
- Oldenburg, J., et al.
(författare)
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Controlled, cross-sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand
- 2015
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 21:2, s. 171-179
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Tidskriftsartikel (refereegranskat)abstract
- In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12-35years were assigned to 1 of 5 groups: primary prophylaxis started at age <2years (group 1); secondary prophylaxis started at age 2 to <6years (group 2), 6 to <12years (group 3), or 12-18years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n=118). All prophylaxis groups had better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of prophylaxis. Ankles were the most affected joints. In group 1 patients currently aged 27-35years, the median of maximum ankle scores was 0.0; corresponding values in groups 4 and 5 were 17.0 and 18.0, respectively [medians of mean index joint scores: 0.0 (group 1), 8.1 (group 2) and 13.8 (group 4)]. Gilbert scores revealed outcomes less pronounced than MRI scores. MRI scores identified pathologic joint status with high sensitivity. Prophylaxis groups had lower annualized joint bleeds and MRI scores vs. the on-demand group. Primary prophylaxis demonstrated protective effects against joint deterioration compared with secondary prophylaxis.
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| 10. |
- Oldenburg, J., et al.
(författare)
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Potential biomarkers of haemophilic arthropathy : correlations with compatible additive magnetic resonance imaging scores
- 2016
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 22:5, s. 760-764
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although biomarkers are useful diagnostic tools to assess joint damage in osteoarthritis and rheumatoid arthritis, few data exist for biomarkers of haemophilic arthropathy. Aim: To evaluate the association between biomarkers and compatible additive magnetic resonance imaging (MRI) scores in patients with severe haemophilia A. Methods: Patients aged 12–35 years with no history of factor VIII (FVIII) inhibitors were enrolled in a controlled, cross-sectional, multinational investigation. Patients received primary or secondary prophylaxis or on-demand treatment with FVIII and underwent MRI on four joints (two ankles, two knees). Soluble biomarkers of cartilage and bone degradation, inflammation, and angiogenesis were assessed (serum levels of C-terminal telopeptides of type I collagen [CTX-I], cartilage oligomeric matrix protein [COMP], chondroitin-sulphate aggrecan turnover 846 epitope [CS846], tissue inhibitor of metalloproteinase 1 [TIMP-1]; plasma levels of vascular endothelial growth factor [VEGF], matrix metalloproteinases 3 and 9 [MMP3, MMP9]). Relationships between biomarkers and MRI scores were evaluated using Spearman rank correlation. Results: Biomarkers were assessed in 117 of 118 per-protocol patients. Mean and median CTX-I, COMP, TIMP-1, MMP3, MMP9, and VEGF values were within normal ranges (reference range not available for CS846 in healthy volunteers). No correlations between biomarkers and MRI scores were found, with the exception of CS846, which showed significant correlation in a subgroup of 22 on-demand patients (r = 0.436; P = 0.04). Conclusions: Compatible additive MRI scores showed no clear correlations with any of the potential biomarkers for haemophilic arthropathy in the overall population. CS846 levels were significantly correlated with MRI scores in patients treated on demand.
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