To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and ...overall survival.
We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).
Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio HR, 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR 95% CI, 0.49 0.29-0.84 and 0.44 0.21-0.89, respectively; P=.009 and P=.02, respectively).
Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
Biological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of ...administration affects patients' treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients' appreciation. Thus, the Belgian Be-raise survey aimed to examine whether RA patient's experience of their current biological treatment coincided with the treating physician's perception. A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient's perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient. Completed questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored greater than or equal to 9) than that of the treating physician (35%), regardless of the route of administration (p< 0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician's perception of patient's satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p< 0.001).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the ...European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.
Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human ...Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility.
We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument.
Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming.
The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. The eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument.
Background
In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour-inducing medication can carry considerable ...risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan.
Methods
A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment.
Results
Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7–9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5–6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0–3.1).
Conclusions
In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required.
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