Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling

This article is made available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/Introduction: Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis. Methods: Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case.National Institute for Health Research Health Technology Assessment (NIHR HTA) Programm

Protention and retention in biological systems

This paper proposes an abstract mathematical frame for describing some features of cognitive and biological time. We focus here on the so called "extended present" as a result of protentional and retentional activities (memory and anticipation). Memory, as retention, is treated in some physical theories (relaxation phenomena, which will inspire our approach), while protention (or anticipation) seems outside the scope of physics. We then suggest a simple functional representation of biological protention. This allows us to introduce the abstract notion of "biological inertia".Comment: This paper was made possible only as part of an extended collaboration with Francis Bailly (see references), a dear friend and "ma\^itre \'a penser", who contributed to the key ideas. Francis passed away in february 2008: we continue here our inspiring discussions and joint wor

The influence of competing root symbionts on below-ground plant resource allocation

1. Plants typically interact with multiple above- and below-ground organisms simultaneously, with their symbiotic relationships spanning a continuum ranging from mutualism, such as with arbuscular mycorrhizal fungi (AMF), to parasitism, including symbioses with plant-parasitic nematodes (PPN). 2. Although research is revealing the patterns of plant resource allocation to mutualistic AMF partners under different host and environmental constraints, the root ecosystem, with multiple competing symbionts, is often ignored. Such competition is likely to heavily influence resource allocation to symbionts. 3. Here, we outline and discuss the competition between AMF and PPN for the finite supply of host plant resources, highlighting the need for a more holistic understanding of the influence of below-ground interactions on plant resource allocation. Based on recent developments in our understanding of other symbiotic systems such as legume–rhizobia and AMF-aphid-plant, we propose hypotheses for the distribution of plant resources between contrasting below-ground symbionts and how such competition may affect the host. 4. We identify relevant knowledge gaps at the physiological and molecular scales which, if resolved, will improve our understanding of the true ecological significance and potential future exploitation of AMF-PPN-plant interactions in order to optimize plant growth. To resolve these outstanding knowledge gaps, we propose the application of well-established methods in isotope tracing and nutrient budgeting to monitor the movement of nutrients between symbionts. By combining these approaches with novel time of arrival experiments and experimental systems involving multiple plant hosts interlinked by common mycelial networks, it may be possible to reveal the impact of multiple, simultaneous colonizations by competing symbionts on carbon and nutrient flows across ecologically important scales

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

Background: Mycoplasma genitalium is a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations in M. genitalium among the sexually-active British general population. / Methods: The third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16–74 years in Britain conducted during 2010–12. Urine test results for M. genitalium were available for 4507 participants aged 16–44 years reporting >1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA and parC genes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively. / Results: 94% (66/70) of specimens were re-confirmed as M. genitalium positive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) for parC genes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and in parC (encoding ParC D87N/D87Y) in 3.3% (0.9%–11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%–73.3%) vs 10.6% (4.6%–22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%–66.8%) vs 5.0% (1.4%–16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms. / Conclusions This study highlights challenges in M. genitalium management and control. Macrolide resistance was present in one in six specimens from the general population in 2010–2012, but no participants with AMR M. genitalium reported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended

Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic considerations

Background Writing therapy to improve physical or mental health can take many forms. The most researched model of therapeutic writing (TW) is unfacilitated, individual expressive writing (written emotional disclosure). Facilitated writing activities are less widely researched. Data sources Databases including: MEDLINE, EMBASE, PsychINFO, Linguistics and Language Behavior Abstracts, AMED, and CINHAL were searched from inception to March 2013. Review methods Four TW practitioners provided expert advice. Study procedures were conducted by one reviewer and checked by a second. Randomised controlled trials (RCTs) and non-randomised comparative studies were included. Quality was appraised using the Cochrane risk of bias tool. Unfacilitated and facilitated TW studies were analysed separately under ICD-10 chapter headings. Meta-analyses were performed where possible using Revman 5.2. Costs were estimated from an NHS perspective and three cost-consequence case studies were prepared. Realist synthesis followed RAMESES guidelines. Objectives To review the clinical and cost-effectiveness of TW for people with long-term health conditions (LTCs) compared to no writing, or other controls, reporting any relevant clinical outcomes. To conduct a realist synthesis to understand how TW might work, and for whom. Results From 14,658 unique citations, 284 full text papers were reviewed and 64 studies (58 RCTs) were included in the final effectiveness reviews. Five studies examined facilitated TW, these were extremely heterogeneous with unclear or high risk of bias, but suggested that facilitated TW interventions may be beneficial in individual LTCs. Unfacilitated expressive writing was examined in 59 studies of variable, or unreported, quality. Overall there was very little or no evidence of any benefit reported in the following conditions (number of studies): HIV (six); breast cancer (eight); gynaecological and genitourinary cancers (five); mental health (five); asthma (four); psoriasis (three); chronic pain (four). In inflammatory arthropathies (six) there was a reduction in disease severity (n= 191, standardised mean difference (SMD) - 0.61 [95% confidence intervals (95% CI) -0.96, -0.26]) in the short term on meta-analysis of four studies. For all other LTCs there was either no, or sparse, data with no, or inconsistent, evidence of benefit. Meta-analyses conducted across all the LTCs provided no evidence that unfacilitated EW had any effect on depression at short term (n= 1,563, SMD -0.06, 95% CI -0.29 to 0.17, substantial heterogeneity), or long term (n= 778, SMD-0.04 95% CI -0.18 to 0.10, little heterogeneity) follow up, or on anxiety, physiological or biomarker-based outcomes. One study reported costs, none reported cost-effectiveness, twelve reported resource use; meta-analysis suggested reduced medication use but no impact on health centre visits. Estimated costs of intervention were low, but there was insufficient evidence to judge cost-effectiveness. Realist review findings suggested that facilitated TW is a complex intervention and group interaction contributes to the perception of benefit. It was unclear from the available data who might benefit most from facilitated TW. Limitations Difficulties with developing realist review programme theory meant that mechanisms operating during TW remain obscure. Conclusions Overall there is little evidence to support the effectiveness or cost-effectiveness of unfacilitated expressive writing interventions in people with LTCs. Further research focussed on facilitated TW in people with LTCs could be informative.The National Institute for Health Research Health Technology Assessment programme

Estimating the Prevalence of Sexual Function Problems: The Impact of Morbidity Criteria

Establishing the clinical significance of symptoms of sexual dysfunction is challenging. To address this, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced two new morbidity criteria (duration and symptom severity) to the existing criteria of distress. This study sought to establish the impact of these three criteria on the population prevalence of sexual function problems. The data come from a national probability survey (Natsal-3) and are based on 11,509 male and female participants aged 16-74, reporting at least one sexual partner in the past year. The key outcomes were: proportion of individuals reporting proxy measures of DSM-5 problems, and the proportion of those meeting morbidity criteria. We found that among sexually active men, the prevalence of reporting one or more of four specific sexual problems was 38.2%, but 4.2% after applying the three morbidity criteria; corresponding figures for women reporting one or more of three specific sexual problems, were 22.8% and 3.6%. Just over a third of men and women reporting a problem meeting all three morbidity criteria had sought help in the last year. We conclude that the DSM-5 morbidity criteria impose a focus on clinically significant symptoms

Is chlamydia screening and testing in Britain reaching young adults at risk of infection? Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

In the context of widespread opportunistic chlamydia screening among young adults, we aimed to quantify chlamydia testing and diagnosis among 16-24 year olds in Britain in relation to risk factors for prevalent chlamydia infection

Screening for gonorrhoea using samples collected through the English National Chlamydia Screening Programme and risk of false positives: a national survey of Local Authorities

OBJECTIVES: To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England. DESIGN AND SETTING: During May-July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15-24 years. MAIN OUTCOME MEASURES: (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%. RESULTS: 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450-4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17-67%. CONCLUSIONS: Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed