Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews

Background Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS)is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain.ObjectivesTo provide an overview of evidence from Cochrane Reviews of theeffectiveness of TENS to reduce pain in adults with chronic pain(excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine)with a view to recommending strategies to reduce any uncertainty. Methods Search methods We searched the Cochrane Database of Systematic Reviews(CDSR), in the Cochrane Library, across all years up to Issue 11 of12, 2018. Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. Weincluded all Cochrane Reviews of randomised controlled trials(RCTs) assessing the effectiveness of TENS in people with chronic pain.We included reviews if they investigated the following: TENSversus sham; TENS versus usual care or no treatment/waiting list control;TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS deliveredusing different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judge-ments where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects;our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impressionof change.Main results We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achievedoverall high scores on the AMSTAR checklist. The evidence reportedwithin each review was consistently rated as very low quality.Using review authors’ assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD−1.58, 95%CI−2.08 to−1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants).However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD−0.85, 95% CI−1.36 to−0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham andno intervention data to be problematic since we would predict these different comparisons may be estimating different trueeffects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions.Authors’ conclusions We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were the reforeunable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability,health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic painNational Institute for Health Research,via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS

Improving the management of pain from advanced cancer in the community: study protocol for a pragmatic multi-centre randomised controlled trial

Introduction: For patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multi-centre randomised controlled trial to assess feasibility, acceptability, effectiveness and cost effectiveness for a multi-component intervention for pain management in patients with advanced cancer. Methods and Analysis: This trial will assess the feasibility of implementation and uptake of evidence based interventions, developed and piloted as part of the IMPACCT Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient rated pain, patient pain knowledge and experience, healthcare use, quality of life, and cost effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost effectiveness. Outcome assessment will be blinded and patient reported outcome measures collected via post at 6 and 12 weeks following randomisation. Ethics and Dissemination: This RCT has the potential to significantly influence NHS service delivery to community based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically and cost effective additions to standard community palliative care

Differential Adhesive Properties of Sequestered Asexual and Sexual Stages of Plasmodium falciparum on Human Endothelial Cells Are Tissue Independent

The protozoan parasite Plasmodium falciparum, responsible for the most severe form of malaria, is able to sequester from peripheral circulation during infection. The asexual stage parasites sequester by binding to endothelial cell receptors in the microvasculature of various organs. P. falciparum gametocytes, the developmental stages responsible for parasite transmission from humans to Anopheles mosquitoes, also spend the almost ten days necessary for their maturation sequestered away from the peripheral circulation before they are released in blood mainstream. In contrast to those of asexual parasites, the mechanisms and cellular interactions responsible for immature gametocyte sequestration are largely unexplored, and controversial evidence has been produced so far on this matter. Here we present a systematic comparison of cell binding properties of asexual stages and immature and mature gametocytes from the reference P. falciparum clone 3D7 and from a patient parasite isolate on a panel of human endothelial cells from different tissues. This analysis includes assays on human bone marrow derived endothelial cell lines (HBMEC), as this tissue has been proposed as a major site of gametocyte maturation. Our results clearly demonstrate that cell adhesion of asexual stage parasites is consistently more efficient than that, virtually undetectable of immature gametocytes, irrespectively of the endothelial cell lines used and of parasite genotypes. Importantly, immature gametocytes of both lines tested here do not show a higher binding efficiency compared to asexual stages on bone marrow derived endothelial cells, unlike previously reported in the only study on this issue. This indicates that gametocyte-host interactions in this tissue are unlikely to be mediated by the same adhesion processes to specific endothelial receptors as seen with asexual forms

Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. DISCUSSION: The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia

Pain self-management interventions for community-based patients with advanced cancer: a research programme including the IMPACCT RCT

Background Each year in England and Wales, 150,000 people die from cancer, of whom 110,000 will suffer from cancer pain. Research highlights that cancer pain remains common, severe and undertreated, and may lead to hospital admissions. Objective To develop and evaluate pain self-management interventions for community-based patients with advanced cancer. Design A programme of mixed-methods intervention development work leading to a pragmatic multicentre randomised controlled trial of a multicomponent intervention for pain management compared with usual care, including an assessment of cost-effectiveness. Participants Patients, including those with metastatic solid cancer (histological, cytological or radiological evidence) and/or those receiving anti-cancer therapy with palliative intent, and health professionals involved in the delivery of community-based palliative care. Setting For the randomised controlled trial, patients were recruited from oncology outpatient clinics and were randomly allocated to intervention or control and followed up at home. Interventions The Supported Self-Management intervention comprised an educational component called Tackling Cancer Pain, and an eHealth component for routine pain assessment and monitoring called PainCheck. Main outcome measures The primary outcome was pain severity (measured using the Brief Pain Inventory). The secondary outcomes included pain interference (measured using the Brief Pain Inventory), participants’ pain knowledge and experience, and cost-effectiveness. We estimated costs and health-related quality-of-life outcomes using decision modelling and a separate within-trial economic analysis. We calculated incremental cost-effectiveness ratios per quality-adjusted life-year for the trial period. Results Work package 1 – We found barriers to and variation in the co-ordination of advanced cancer care by oncology and primary care professionals. We identified that the median time between referral to palliative care services and death for 42,758 patients in the UK was 48 days. We identified key components for self-management and developed and tested our Tackling Cancer Pain resource for acceptability. Work package 2 – Patients with advanced cancer and their health professionals recognised the benefits of an electronic system to monitor pain, but had reservations about how such a system might work in practice. We developed and tested a prototype PainCheck system. Work package 3 – We found that strong opioids were prescribed for 48% of patients in the last year of life at a median of 9 weeks before death. We delivered Medicines Use Reviews to patients, in which many medicines-related problems were identified. Work package 4 – A total of 161 oncology outpatients were randomised in our clinical trial, receiving either supported self-management (n = 80) or usual care (n = 81); their median survival from randomisation was 53 weeks. Primary and sensitivity analyses found no significant treatment differences for the primary outcome or for other secondary outcomes of pain severity or health-related quality of life. The literature-based decision modelling indicated that information and feedback interventions similar to the supported self-management intervention could be cost-effective. This model was not used to extrapolate the outcomes of the trial over a longer time horizon because the statistical analysis of the trial data found no difference between the trial arms in terms of the primary outcome measure (pain severity). The within-trial economic evaluation base-case analysis found that supported self-management reduced costs by £587 and yielded marginally higher quality-adjusted life-years (0.0018) than usual care. However, the difference in quality-adjusted life-years between the two trial arms was negligible and this was not in line with the decision model that had been developed. Our process evaluation found low fidelity of the interventions delivered by clinical professionals. Limitations In the randomised controlled trial, the low fidelity of the interventions and the challenge of the study design, which forced the usual-care arm to have earlier access to palliative care services, might explain the lack of observed benefit. Overall, 71% of participants returned outcome data at 6 or 12 weeks and so we used administrative data to estimate costs. Our decision model did not include the negative trial results from our randomised controlled trial and, therefore, may overestimate the likelihood of cost-effectiveness. Conclusions Our programme of research has revealed new insights into how patients with advanced cancer manage their pain and the challenges faced by health professionals in identifying those who need more help. Our clinical trial failed to show an added benefit of our interventions to enhance existing community palliative care support, although both the decision model and the economic evaluation of the trial indicated that supported self-management could result in lower health-care costs. Future work There is a need for further research to (1) understand and facilitate triggers that prompt earlier integration of palliative care and pain management within oncology services; (2) determine the optimal timing of technologies for self-management; and (3) examine prescriber and patient behaviour to achieve the earlier initiation and use of strong opioid treatment. Trial registration Current Controlled Trials ISRCTN18281271. Funding This project was funded by the National Institute for Health Research Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 15. See the NIHR Journals Library website for further project information

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research