Claims for fertility interventions: a systematic assessment of statements on UK fertility centre websites.

OBJECTIVES: Fertility services in the UK are offered by over 200 Human Fertilisation and Embryology Authority (HFEA)-registered NHS and private clinics. While in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) form part of the National Institute for Health and Care Excellence (NICE) guidance, many further interventions are offered. We aimed to record claims of benefit for interventions offered by fertility centres via information on the centres' websites and record what evidence was cited for these claims. METHODS: We obtained from HFEA a list of all UK centres providing fertility treatments and examined their websites. We listed fertility interventions offered in addition to standard IVF and ICSI and recorded statements about interventions that claimed or implied improvements in fertility in healthy women. We recorded which claims were quantified, and the evidence cited in support of the claims. Two reviewers extracted data from websites. We accessed websites from 21 December 2015 to 31 March 2016. RESULTS: We found 233 websites for HFEA-registered fertility treatment centres, of which 152 (65%) were excluded as duplicates or satellite centres, 2 were andrology clinics and 5 were unavailable or under construction websites. In total, 74 fertility centre websites, incorporating 1401 web pages, were examined for claims. We found 276 claims of benefit relating to 41 different fertility interventions made by 60 of the 74 centres (median 3 per website; range 0 to 10). Quantification was given for 79 (29%) of the claims. 16 published references were cited 21 times on 13 of the 74 websites. CONCLUSIONS: Many fertility centres in the UK offer a range of treatments in addition to standard IVF procedures, and for many of these interventions claims of benefit are made. In most cases, the claims are not quantified and evidence is not cited to support the claims. There is a need for more information on interventions to be made available by fertility centres, to support well-informed treatment decisions.

The measurement of patients' expectations for health care: a review and psychometric testing of a measure of patients' expectations.

BACKGROUND: There is recognition of the importance of measuring patients' experiences, expectations and satisfaction. OBJECTIVES: To assess the literature on the concept and measurement of patients' expectations for health care, and to develop and test a measure of patients' expectations, using adult patients in community, general practice and hospital outpatient departments in Greater London, Norwich and Essex, UK. DATA SOURCES: Major electronic databases including the British Nursing Index, EMBASE, MEDLINE, PsycINFO and the Applied Social Sciences Index and Abstracts were searched between 2000 and 2009. REVIEW METHODS: Narrative review, semi-structured exploratory study and surveys of GP patients and hospital outpatients immediately before and after their surgery/clinic visit to measure their pre-visit expectations for their health care and their post-visit experiences (expectations met and satisfaction with visit) (site specific). RESULTS: A total of 20,439 titles and 266 abstracts were identified, of which 211 were included in the review. Most research designs were weak, with small or selected samples, and a theoretical frame of reference was rarely stated. The origin of questions about expectations was often absent, questions were frequently untested and those with reported reliability or validity data had generally mixed results. In the survey data the expectations measures met acceptability criteria for reliability; all exceeded the threshold of α = 0.70, in each mode of administration and sample type. Items and subscales also correlated at least moderately with those variables that they were expected to be associated with, supporting their validity. The item means within subscales were generally similar between samples and all-item-total correlations exceeded the acceptability threshold. Descriptive findings revealed that most patients ideally expected cleanliness, information about where to go, convenient and punctual appointments and helpful reception staff, the doctor to be knowledgeable, clear and easy to understand, to be involved in treatment decisions and to experience a reduction in symptoms/problems. Expectations least likely to be met included being seen on time and choice of hospital/doctor (items requested by the ethics committee). Other items that had low met expectations included helpfulness of reception staff, doctor being respectful and treating with dignity (hospital sample), doctor knowledgeable (hospital), being given reassurance, receiving advice about health/condition, information about cause and management of condition and information about benefits/side effects of treatment, being given an opportunity to discuss problems, and the three items on outcome expectancies. Previous consultations/experiences of health services and health-care staff/professionals most commonly influenced expectations. Overall, pre-visit realistic expectations were lower than patients' ideals or hopes. Most post-visit experiences indicated some unmet expectations (e.g. cause and management of health/condition, benefits/side effects of treatments) and some expectations that were exceeded. Generally, GP patients reported higher pre-visit expectations and post-visit met expectations. Correlations between subscale domains were strongest between the structure and process of health care, doctor-patient communication style and doctor's approach to giving information, all common indicators of the quality of health care, supporting the validity of the measures. The post-visit experiences subscale significantly predicted single-item summary ratings of overall met expectations and satisfaction. GP rather than hospital patients were also independently predictive of expectations met. Other predictors were having no/little anxiety/depression, older age (satisfaction) and fewer effects of health on quality of life (met expectations). LIMITATIONS: The surveys in clinics were based on convenience, not random sampling methods. CONCLUSIONS: These findings have implications for establishing the quality of health services and informing their improvement. Awareness of the patient's met and unmet expectations should enable staff to understand the patient's perspective and improve communication. This study examined the perspective of the patient only; it is not possible to examine the extent to which any expectations might have been unrealistically too high or too low. This is a challenge for future research. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the National Co-ordinating Centre for Research Methodology (NCCRM).

Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability.

Signal transduction pathways regulate gene expression in part by modulating the stability of specific mRNAs. For example, the mitogen-activated protein kinase (MAPK) p38 pathway mediates stabilization of tumor necrosis factor alpha (TNF-alpha) mRNA in myeloid cells stimulated with bacterial lipopolysaccharide (LPS). The zinc finger protein tristetraprolin (TTP) is expressed in response to LPS and regulates the stability of TNF-alpha mRNA. We show that stimulation of RAW264.7 mouse macrophages with LPS induces the binding of TTP to the TNF-alpha 3' untranslated region. The p38 pathway is required for the induction of TNF-alpha RNA-binding activity and for the expression of TTP protein and mRNA. Following stimulation with LPS, TTP is expressed in multiple, differentially phosphorylated forms. We present evidence that phosphorylation of TTP is mediated by the p38-regulated kinase MAPKAPK2 (MAPK-activated protein kinase 2). Our findings demonstrate a direct link between a specific signal transduction pathway and a specific RNA-binding protein, both of which are known to regulate TNF-alpha gene expression at a posttranscriptional level.

The 3' untranslated region of tumor necrosis factor alpha mRNA is a target of the mRNA-stabilizing factor HuR.

Posttranscriptional regulation is important for tumor necrosis factor alpha (TNF-alpha) expression in monocytes and macrophages, and an AU-rich element (ARE) in the 3' untranslated region (UTR) of TNF-alpha mRNA is implicated in control of its translation and mRNA stability. Regulation of mRNA turnover is thought to be mediated by trans-acting proteins, which bind the ARE and stabilize or destabilize the transcript. However, with the exception of the destabilizing factor tristetraprolin, the identity and function of the proteins binding the TNF-alpha mRNA ARE have not been established. To identify other proteins involved in the posttranscriptional control of TNF-alpha, the subcellular location of TNF-alpha mRNA was determined in the macrophage-like cell line RAW 264.7. TNF-alpha mRNA was located in the pellet following centrifugation of cytoplasm at 100,000 x g (P100 fraction). This fraction also contained proteins which formed two distinct ARE-specific complexes with the TNF-alpha mRNA 3' UTR in electrophoretic mobility shift assays (EMSAs). A protein present in these two complexes was purified and identified by peptide mass mapping and tandem mass spectrometry as HuR. In EMSAs both complexes were supershifted by an anti-HuR antibody, while Western blotting also demonstrated the presence of HuR in the P100 extract. A HeLa cell tetracycline-regulated reporter system was used to determine the effect of HuR on mRNA stability. In this system, overexpression of HuR resulted in stabilization of an otherwise unstable reporter-mRNA containing the TNF-alpha ARE. These results demonstrate that the TNF-alpha ARE is a target of the mRNA-stabilizing factor HuR.

Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade.

A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3' untranslated region (3' UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric beta-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as beta-globin-Cox-2 transcripts were partially stabilized by phosphomimetic mutant forms of hsp27. A short (123-nucleotide) fragment of the Cox-2 3' UTR was necessary and sufficient for the regulation of mRNA stability by the p38 cascade and interacted with a HeLa protein immunologically related to AU-rich element/poly(U) binding factor 1.