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StatementThe authors have withdrawn their manuscript owing to a reporting error that we have identified in the conduct of this updated systematic review. On 7thMarch 2022 we made changes to the original protocol published in F1000, to highlight the need to keep up with the evolving landscape of Covid-19 and Covid-19 research and focus on comparative, controlled studies. The revisions included also changes in data extraction and analysis that would be needed to do so. These changes were done in consultation with members of the Long COVID Support Group. However, we omitted to publicize these changes in an accessible, modified version of our protocol, and/or by updating our preregistered PROSPERO record (CRD42020211131) and F1000 publication, prior to commencing and completing these stages of the process. In this manuscript, which reports the revised analyses, we have consequently also omitted to explicitly describe these changes as important deviations from the published protocol. Additionally, following rapid, sustained, and continuous growth in the conduct and reporting of eligible primary studies, it has become clear that, with or without the changes described above, we do not have sufficient capacity or resources to transition our baseline systematic review to being regularly updated using a living systematic review approach. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Research objective\ud To determine if Muscle Response Testing (MRT) can be used to distinguish lies from truths using blind test patients.\ud \ud Design\ud A prospective study of diagnostic test accuracy was carried out using MRT to distinguish lies from truth.\ud \ud Methods\ud Twenty practitioners who routinely practised MRT were paired with 20 blind test patients (TPs). TPs were asked to speak simple true and false statements about visual stimuli presented subliminally (at 20 ms). In the subliminal phase, pairs performed 20 MRTs and 20 Intuitive Guesses (IG), consisting of 2 blocks of 10 statements each. In the Supraliminal Phase, the same picture-statement pairs were repeated. The order of stimuli presentation was randomly assigned so that each pair was presented with a unique series of stimuli.\ud \ud Results\ud In the Subliminal Phase, MRT accuracy (as percent correct) was found to be 48.5% (95% CI 42.8–54.2), which was no different from IG accuracy (47.8%; 95% CI 43.2–52.3; p = 0.68) or chance (50.0%; p = 0.59), and no different from MRT accuracy during the supraliminal phase (59.0%; 95% CI 50.4–67.6; p = 0.05). However, supraliminal MRT accuracy was significantly different from chance (p = 0.04), indicating that the pairs could perform MRT proficiently.\ud \ud Conclusion\ud The main reason for finding no effect is suspected to be due to an inadequate subliminal methodology, a process which is quite complex. Other explanations of results include: (1) MRT is not a valid test when the TP is blind, (2) Blinding TPs during MRT will produce ambiguous or unpredictable results, or (3) Nonconscious beliefs cannot be elicited using subliminal stimuli. Future research may wish to focus on exploring these possibilities. More specifically, subsequent studies may wish to use different methods to blind TPs, and establish whether MRT can be used to detect nonconscious processes, a generally held consensus among MRT practitioners.

Background and Objectives The growth of trials conducted over the internet has increased, but with little practical guidance for their conduct, and it is sometimes challenging for researchers to adapt the conventions used in face-to-face trials and maintain the validity of the work. The aim of the study is to systematically explore existing self-recruited online randomized trials of self-management interventions and analyze the trials to assess their strengths and weaknesses, the quality of reporting, and the involvement of lay persons as collaborators in the research process. Study Design and Settings The Online Randomized Controlled Trials of Health Information Database was used as the sampling frame to identify a subset of self-recruited online trials of self-management interventions. The authors cataloged what these online trials were assessing, appraised study quality, extracted information on how trials were run, and assessed the potential for bias. We searched out how public and patient participation was integrated into online trial design and how this was reported. We recorded patterns of use for registration, reporting, settings, informed consent, public involvement, supplementary materials, and dissemination planning. Results The sample included 41 online trials published from 2002 to 2015. The barriers to replicability and risk of bias in online trials included inadequate reporting of blinding in 28/41 (68%) studies; high attrition rates with incomplete or unreported data in 30/41 (73%) of trials; and 26/41 (63%) of studies were at high risk for selection bias as trial registrations were unreported. The methods for (23/41, 56%) trials contained insufficient information to replicate the trial, 19/41 did not report piloting the intervention. Only 2/41 studies were cross-platform compatible. Public involvement was most common for advisory roles (n = 9, 22%), and in the design, usability testing, and piloting of user materials (n = 9, 22%). Conclusion This study catalogs the state of online trials of self-management in the early 21st century and provides insights for online trials development as early as the protocol planning stage. Reporting of trials was generally poor and, in addition to recommending that authors report their trials in accordance with CONSORT guidelines, we make recommendations for researchers writing protocols, reporting on and evaluating online trials. The research highlights considerable room for improvement in trial registration, reporting of methods, data management plans, and public and patient involvement in self-recruited online trials of self-management interventions.

Muscle response testing (MRT) is an assessment method used by 1 million practitioners worldwide, yet its usefulness remains uncertain. The aim of this study, one in a series assessing the accuracy of MRT, was to determine whether emotionally arousing stimuli influence its accuracy compared to neutral stimuli.To assess diagnostic test accuracy 20 MRT practitioners were paired with 20 test patients (TPs). Forty MRTs were performed as TPs made true and false statements about emotionally arousing and neutral pictures. Blocks of MRT alternated with blocks of intuitive guessing (IG).MRT accuracy using emotionally arousing stimuli was different than when using neutral stimuli. However, MRT accuracy was found to be significantly better than IG and chance. Similar to previous studies in this series, this study failed to detect any characteristic that consistently influenced MRT accuracy.Using emotionally arousing stimuli had no effect on MRT accuracy compared to using neutral stimuli. This study would have been strengthened by adding personally relevant lies instead of impersonal stimuli. A limitation of this study is its lack of generalizability to other applications of MRT. This study shows that a simple yet robust methodology for assessing MRT as a diagnostic tool can be implemented effectively.Einleitung: Die Muskelreaktionstestung (MT) ist eine Untersuchungsmethode, die weltweit von einer Million Praktikern angewendet wird, deren Nutzen jedoch unklar ist. Mit der vorliegenden Studie (die zu einer Serie von Studien zur Bewertung der MT gehörte) sollte untersucht werden, ob emotional erregende Reize die Testgenauigkeit im Vergleich zu neutralen Reizen beeinflussen. Me­thoden: Zur Bestimmung der diagnostischen Testge­nauigkeit wurden 20 MT-Praktiker und 20 Testpersonen (TPs) gepaart und 40 MTs durchgeführt, bei denen die TPs wahre und falsche Aussagen über emotional erregende und neutrale Abbildungen machten. Dabei wurden ab­wechselnd Blöcke mit MT und Blöcke mit intuitivem Raten (“intuitive guessing”) verwendet. Ergebnisse: Die Genauigkeit der MT fiel bei Verwendung emotional erregender Reize anders aus als bei Verwendung neutraler Reize. Allerdings war die Genauigkeit der MT signifikant höher als bei intuitivem Raten und rein zufälliger Auswahl. Ähnlich wie in den vorherigen Studien dieser Serie fand sich auch in dieser Studie kein Merkmal mit einheitlichen Auswirkungen auf die MT-Genauigkeit. Schlussfolgerung: Die Verwendung emotional erregender Reize hatte im Vergleich zu neutralen Reizen keinen Einfluss auf die Genauigkeit der MT. Die Aussagekraft der Studie wäre höher gewesen, wenn individuell relevante Lügen anstelle von unpersönlichen Reizen verwendet worden wären. Eine Einschränkung der Studie besteht in ihrer fehlenden Verallgemeinerbarkeit auf andere MT-Anwendungen. Die Studie zeigt, dass sich die MT als diagnostisches Instrument mit einer einfachen, jedoch robus­ten Methode wirksam beurteilen lässt.

BackgroundWhile it is now apparent clinical sequelae (often called Long Covid) may persist after acute Covid-19, their nature, frequency, and aetiology are poorly characterised. This study aims to regularly synthesise evidence on Long Covid characteristics, to inform clinical management, rehabilitation, and interventional studies to improve long term outcomes.MethodsA living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on Covid-19, LitCOVID, and Google Scholar were searched up to 17th March 2021. Published studies including at least 100 people with confirmed or clinically suspected Covid-19 at 12 weeks or more post-onset were included. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence with 95% confidence intervals (CIs).ResultsThirty-nine studies were included: 32 cohort, six cross-sectional, and one case-control. Most showed high or moderate risk of bias. None were set in low-income countries, limited studies included children. Studies reported on 10,951 people (48% female) in 12 countries. Most followed-up post hospital discharge (78%, 8520/10951). The longest mean follow-up was 221.7 (SD: 10.9) days post Covid-19 onset. An extensive range of symptoms with wide prevalence was reported, most commonly weakness (41%; 95% CI 25% to 59%), malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%), and breathlessness (25%; 95% CI 18% to 34%). Other frequent symptoms included musculoskeletal, neurological, and psychological. 37% (95% CI 18% to 60%) of people reported reduced quality of life.ConclusionLong Covid is a complex condition with heterogeneous symptoms. The nature of the studies precludes a precise case definition or evaluation of risk factors. There is an urgent need for prospective, robust, standardised controlled studies into aetiology, risk factors, and biomarkers to characterise Long Covid in different at-risk populations and settings.Systematic review registrationThe protocol was prospectively registered on the PROSPERO database (CRD42020211131).Section 1: What is already known?A significant number of people continue to describe ongoing symptoms long after the acute phase of Covid-19, often referred to as Long Covid.Long Covid is a heterogeneous condition with an uncertain prevalence, for which there is currently no precise case definition.Section 2: What are the new findings?This ‘living’ systematic review provides a comprehensive summary of peer-reviewed published evidence on persistent symptoms of Covid-19 and will be regularly updated as new evidence emerges.The breadth of reported symptoms suggests a complex, heterogeneous condition affecting both those who were hospitalised and those managed in the community.Our review identifies weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% confidence interval 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%) as the most common symptoms.Section 3: What do the new findings imply?The current evidence base of the clinical spectrum of Long Covid is limited, based on heterogenous data, and vulnerable to biases, hence caution should be used when interpreting or generalising the results.Our review identifies areas where further Long Covid research is critically needed to help characterise Long Covid in different populations and define its aetiology, risk factors, and biomarkers, as well as the impact on variants of concern and vaccination on long term outcomes.

Making good public health decisions requires integrating relevant local knowledge about your population with national guidance and best research evidence. However, public health research evidence is more diverse than clinical research and needs to be sought in a much wider range of information sources. Furthermore, evidence comes from a range of different study types, which adds a further challenge when assessing the quality of the research. This chapter has two aims. The first is to help you find research evidence efficiently, so that you can access the best, most relevant research evidence for your research query. The second is to help you make sense of research through the technique of critical appraisal, which is the systematic assessment of research evidence. Finding and appraising evidence is an essential skill in the process of improving the health of the population.

This chapter aims to: describe the methodological and communication challenges in investigating allegations of environmentally related disease clusters; provide public health practitioners with a structured and systematic approach to preparing for, and responding effectively and appropriately to, such allegations.

Although the majority of people with Covid-19 will experience mild to moderate symptoms and will recover fully, there is now increasing evidence that a significant proportion will experience persistent symptoms for months after the acute phase of the illness. These symptoms include, among others, fatigue, problems breathing, lack of smell and taste, headaches, and depression and anxiety. It is also clear the virus has lasting fluctuating multiorgan sequelae, including affecting not only the respiratory system but also the heart, liver, and nervous system. We present a protocol for a living systematic review that aims to synthesize the evidence on the prevalence and characteristics of post-acute COVID-19. The living systematic review will be updated regularly, approximately every 6 months, as new evidence emerges. We will include studies that follow up at least 100 people with Covid-19 at 12 or more weeks post Covid-19 onset, with no restrictions regarding country, setting, or language. We will use descriptive statistics and, for outcomes reported in two or more studies, we will use meta-analyses to estimate prevalence with 95% confidence intervals (CIs) using the exact method. Heterogeneity between estimates will be assessed using the I2 statistic. Our findings will also be presented as infographics to facilitate transcription to lay audiences. Ultimately, we aim to support the work of policy makers, practitioners, and patients when planning rehabilitation for those recovering from Covid-19. The protocol has been registered with PROSPERO ( CRD42020211131, 25/09/2020).

BACKGROUND The prevalence and consequences of obesity among children and adolescents remain a leading global public health concern, and evidence-based, multidisciplinary lifestyle interventions are the cornerstone of treatment. Mobile electronic devices are widely used across socioeconomic categories and may provide a means of extending the reach and efficiency of health care interventions. OBJECTIVE We aimed to synthesize the evidence regarding mobile health (mHealth) for the treatment of childhood overweight and obesity to map the breadth and nature of the literature in this field and describe the characteristics of published studies. METHODS We conducted a systematic scoping review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, by searching nine academic databases in addition to gray literature for studies describing acceptability, usability, feasibility, effectiveness, adherence, or cost-effectiveness of interventions assessing mHealth for childhood obesity treatment. We also hand searched the reference lists of relevant articles. Studies aimed at the prevention of overweight or obesity were excluded, as were studies in which mHealth was not the primary mode of treatment delivery for at least one study arm or was not independently assessed. A random portion of all abstracts and full texts was double screened by a second reviewer to ensure consistency. Data were charted according to study characteristics, including design, participants, intervention content, behavior change theory (BCT) underpinning the study, mode of delivery, and outcomes measured. RESULTS We identified 42 eligible studies assessing acceptability (n=7), usability (n=2), feasibility or pilot studies (n=15), treatment effect (n=17), and fidelity (n=1). Change in BMI z-scores or percentiles was most commonly measured, among a variety of dietary, physical activity, psychological, and usability or acceptability measures. SMS, mobile apps, and wearable devices made up the majority of mobile interventions, and 69% (29/42) of the studies specified a BCT used. CONCLUSIONS Pediatric weight management using mHealth is an emerging field, with most work to date aimed at developing and piloting such interventions. Few large trials are published, and these are heterogeneous in nature and rarely reported according to the Consolidated Standards of Reporting Trials for eHealth guidelines. There is an evidence gap in the cost-effectiveness analyses of such studies. CLINICALTRIAL

Background The Self-Management Open Online Trials in Health (SMOOTH) survey reports methods as well as researcher preferences in online trials and explores to what extent public and participant involvement in online trials occurs. This survey queried researchers’ experience in online trials and their perceived value of public and patient research involvement. The preparation, consideration, and publication of research involvement require the use of resources by the authors. The survey explores whether authors consider resources to be sufficient or useful to improve online trials about self-management of health. Objective To identify the present state of public research involvement in online trials concerning health self-management and to explore the needs of researchers when contemplating the building and writing up an online trials protocol. Methods The ORCID database of online trials was used to survey corresponding authors concerning trial methods and preferences including the frequency, format, and quality of citizen involvement in online trials about health self-management. Results Blended trials were reported as online trials. Remote recruitment and communications were less common than local recruitment even when participants signed up online. Research volunteers helped more with recruitment and as advisors than with trial design, analysis, or outcome setting. Forty-seven percent of Corresponding authors report that an online trial was the best way of answering their research question. Conclusions Detailed reporting of online methods and volunteer researcher involvement was hindered by role confusion between research volunteers and trial participants. Respondents were responsive to the development of protocol and reporting suggestions but were not in favor of adopting complex new frameworks that require extensive time, training, space, and funding.

Rationale, aims and objectives Evidence-based practice (EBP) is widely promoted, but does EBP produce better patient outcomes? We report a natural experiment when part of the internal medicine service in a hospital was reorganized in 2003 to form an EBP unit, the rest of the service remaining unchanged. The units attended similar patients until 2012 permitting comparisons of outcomes and activity. Methods We used routinely collected statistics (2004-11) to compare the two different methods of practice and test whether patients being seen by the EBP unit differed from standard practice (SP) patients. Data were available by doctor and year. To check for differences between the EBP and SP doctors prior to reorganization, we used statistics from 2000 to 2003. We looked for changes in patient outcomes or activity following reorganization and whether the EBP unit was achieving significantly different results from SP. Data across the periods were combined and tested using Mann-Whitney test. Results No statistically significant differences in outcomes were detected between the EBP and the SP doctors prior to reorganization. Following the unit's establishment, the mortality of patients being treated by EBP doctors compared with their previous performance dropped from 7.4% to 6.3% (P Conclusion The EBP unit was associated with better patient outcomes and more efficient performance than achieved by the same physicians previously or by SP concurrently.

Clinical Bottom Line Water intake is a cost effective, non-invasive and low-risk intervention to reduce or prevent headache pain. Rationale: Chronic mild dehydration may trigger headache. Increased water intake could help. A small trial shows modest benefit; however, a larger methodologically sound randomized controlled trial is needed to confirm efficacy. Critically Appraised Paper Spigt, M., Weerkamp, N., Troost, J., van Schayck, C. P., & Knottnerus, J. A. (2012). ‘A randomized trial on the effects of regular water intake in patients with recurrent headaches.’ Family practice, 29(4), 370–5. Doi: 10.1093/fampra/cmr112 Clinical scenario Patients from primary care registered as ‘headache’, ‘tension headache’ and/or ‘migraine’ for more than one year who suffer at least two episodes of moderately intense headache or more than four mildly intense episodes of headache per month with a daily fluid intake of less than 2.5 litres per day. PICO (M) Patient/Problem = Headache > 1 year with 2 moderately intense or 4 mildly intense episodes per month Intervention = 1.5 litres water per day + stress control and sleep hygiene Comparison/Control = stress control and sleep hygiene Outcome = Reduce or eliminate headache Methodology = Therapy RCT Table 1: Final Search Terms TRIP Data Base: hits = 517 used filter Extended Primary research 4 found 1 paper applicable; 'Water intake '[MeSH Terms] AND 'Headache '[All Fields]'; Best match to PICO, (2012) RCT Selection Criterion and Overall Results 102 headache patients in16 primary care clinics were randomized into control (n = 50) and intervention groups (n = 52) Inclusion criteria = two > episodes of moderately intense headache or five > mildly intense headaches per month and total fluid intake > 2.5 litres per day, Follow-up @ 3 months. 79% intervention and 66% of controls completed RCT. Drinking more water resulted in a statistically significant improvement of 4.5 (confidence interval: 1.3–7.8) points on Migraine-Specific Quality of Life (MSQOL). 47% in the intervention (water) group self-reported improvement (6 > on a 10-point scale) against 25% in controls. Drinking water did not reduce headache days. Comments The transparency from the author of this critically appraised paper enables others to use this study as a teaching tool and to learn from the shortcomings in the trial. The study was underpowered and contains methodological shortcomings. Participants were partially un-blinded during the trial increasing the risk for bias. Only the subjective measures are statistically significant and attrition was significant. The intervention is low risk and of negligible cost. A methodologically sound RCT is recommended to evaluate if the intervention has beneficial effects.

Introductions Although DMT is primarily used in the diagnosis of neuromusculoskeletal (NMS) disorders, previous studies have attempted to use other forms of manual muscle testing (MMT) to detect conditions other than NMS. For instance, muscle response testing (MRT) was used to distinguish lies (a known stressor) from truth. Therefore, it is hypothesised that DMT might be used to detect deceit as well, and the aim of this study was to investigate if grip strength via dynamometric muscle testing (DMT) could be used to distinguish lies from truth. Methods A prospective study of diagnostic test accuracy was carried out. Twenty participants, aged 18–65 years, with healthy hands, were recruited. Participants were given a visual stimulus and followed an auditory instruction to lie or to tell the truth about the stimulus, before recording grip strength with a dynamometer. Testing proceeded in this manner until 20 DMTs were performed, 10 by each hand. We analysed the accuracy of grip strength for detecting lies. Results The mean grip strength after true statements was found to be 24.9 kg (95% CI 20.3 to 29.6), and after false statements, 24.8 (95% CI 20.2 to 29.5), which were not statistically different (p = 0.61). Conclusion DMT via hand-held grip strength dynamometry failed to distinguish lies from truth. These results seem to suggest that strength as measured by DMT is not impacted by deceit. A limitation of this study is it is not generalisable to other types or applications of MMT or MRT or to other target conditions.

BACKGROUND: The use of public engagement and self-management in online clinical trials is growing with benefits, boundaries and minimal methodological guidance. This analysis explores whether running self-recruited online trials can provide trustworthy and useful answers to research questions. AIM: To systematically explore existing self-recruited online randomized controlled trials of self-management interventions and analyze the trials to assess their strengths and weaknesses, the quality of trials reporting and to report how participants were involved in the research process. METHODS: The Online Randomized Controlled Trials of Health Information Database (ORCHID) will be used as a sampling framework to identify a subset of self-management self-recruited interventions. The trials will be used to explore the qualities of self-recruited online randomized controlled trials and to evaluate how useful they are for obtaining trustworthy answers to questions about health self-management and citizen research involvement. This research employs participatory action research where researchers and participants work as collaborators. SUMMARY: This analysis can provide an overall view of effective methods for online trials and to provide insights into integration for online trials development as early as the protocol planning stage.

de Epidemiologi´a Cli´nica, CASPe, CIBER-ESP, Hospital Universitario Donostia, San Sebastia´n, Guipu´zcoa, Espan˜aSenior Clinical Research Fellow, Department of Primary Care Health Sciences, Founder and former Director of the International Programme in Evidence Based Health Care,Oxford University, Oxford, Reino Unido

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of drinking extra water or other non-caloric beverages for promoting weight loss or preventing weight gain.

BackgroundTotal pancreatectomy and islet autotransplantation (TP/IAT) is a treatment option in a subset of patients with chronic pancreatitis. A systematic review of the literature was performed to evaluate the outcome of this procedure, with an attempt to ascertain when it is indicated.MethodsMEDLINE (1950 to present), Embase (1980 to present) and the Cochrane Library were searched to identify studies of outcomes in patients undergoing TP/IAT. Cohort studies that reported the outcomes following the procedure were included. The MOOSE guidelines were used as a basis for this review.ResultsFive studies met the inclusion criteria. The techniques reported for pancreatectomy and islet cell isolation varied between studies. TP/IAT was successful in reducing pain in patients with chronic pancreatitis. Comparing morphine requirements before and after the procedure, two studies recorded significant reductions. Concurrent IAT reduced the insulin requirement after TP; the rate of insulin independence ranged from 46 per cent of patients at 5 years' mean follow-up to 10 per cent at 8 years. The impact on quality of life was poorly reported. The studies reviewed did not provide evidence for optimal timing of TP/IAT in relation to the evolution of chronic pancreatitis.ConclusionThis systematic review showed that TP/IAT had favourable outcomes with regard to pain reduction. Concurrent IAT enabled a significant proportion of patients to remain independent of insulin supplementation.

Background: Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe. Methods: We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM. Results: One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering. Conclusions: All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.

Water intake is a cost effective, non-invasive and low-risk intervention to reduce or prevent headache pain.Chronic mild dehydration may trigger headache. Increased water intake could help. A small trial shows modest benefit; however, a larger methodologically sound randomized controlled trial is needed to confirm efficacy.Spigt, M., Weerkamp, N., Troost, J., van Schayck, C. P.,Knottnerus, J. A. (2012). 'A randomized trial on the effects of regular water intake in patients with recurrent headaches.' Family practice, 29(4), 370-5. Doi: 10.1093/fampra/cmr112 CLINICAL SCENARIO: Patients from primary care registered as 'headache', 'tension headache' and/or 'migraine' for more than one year who suffer at least two episodes of moderately intense headache or more than four mildly intense episodes of headache per month with a daily fluid intake of less than 2.5 litres per day.Patient/Problem = Headache 1 year with 2 moderately intense or 4 mildly intense episodes per month Intervention = 1.5 litres water per day + stress control and sleep hygiene Comparison/Control = stress control and sleep hygiene Outcome = Reduce or eliminate headache Methodology = Therapy RCT Table 1: Final Search Terms TRIP Data Base: hits = 517 used filter Extended Primary research 4 found 1 paper applicable 'Water intake '[MeSH Terms] AND 'Headache '[All Fields]' Best match to PICO, (2012) RCT SELECTION CRITERION AND OVERALL RESULTS: 102 headache patients in16 primary care clinics were randomized into control (n = 50) and intervention groups (n = 52) Inclusion criteria = two episodes of moderately intense headache or five mildly intense headaches per month and total fluid intake 2.5 litres per day, Follow-up @ 3 months. 79% intervention and 66% of controls completed RCT. Drinking more water resulted in a statistically significant improvement of 4.5 (confidence interval: 1.3-7.8) points on Migraine-Specific Quality of Life (MSQOL). 47% in the intervention (water) group self-reported improvement (6 on a 10-point scale) against 25% in controls. Drinking water did not reduce headache days.The transparency from the author of this critically appraised paper enables others to use this study as a teaching tool and to learn from the shortcomings in the trial. The study was underpowered and contains methodological shortcomings. Participants were partially un-blinded during the trial increasing the risk for bias. Only the subjective measures are statistically significant and attrition was significant. The intervention is low risk and of negligible cost. A methodologically sound RCT is recommended to evaluate if the intervention has beneficial effects.

Background: Obesity is a global epidemic. Behavioral change approaches towards improving nutrition, increasing physical activity level, improving sleep, and reducing sitting time are recommended as best practices in adolescent obesity management. However, access to evidence-based treatment is limited and portable technologies such as mobile apps may provide a useful platform to deliver such lifestyle interventions. No evidence-based validated app exists for obesity intervention; therefore, a novel mobile app (Reactivate) was developed for use in the Temple Street W82GO Healthy Lifestyles Program (W82GO). Objective: This study aimed to test the usability (technical effectiveness, efficiency, and user satisfaction) of the Reactivate mobile app in obese adolescents. Methods: Ten adolescents (7 males and 3 females, aged 12-17 years) who had been treated for obesity (>98th percentile for body mass index) at the Temple Street Children's University Hospital were recruited. Participants were given 8 tasks to complete in order to test the technical effectiveness of the app. A research assistant timed the user while completing each task in order to test the relative user efficiency of the app (time-on-task). The tasks fell into 5 categories and required the user to enter personal settings, find and answer surveys, create a message, use the goal setting feature, and enter details regarding their weight and height. In exploration of user satisfaction, each participant completed the standardized software usability measurement inventory (SUMI), which measures 5 aspects of user satisfaction: efficiency, effect, helpfulness, controllability, and learnability. Descriptive statistics were used to explore the mean relative user efficiency and SUMI scores. Results: Mean age was 14.26 (SD 1.58) years. All adolescents completed each of the tasks successfully. The mean relative user efficiency scores were two to three times that of an expert user. Users responded that they would use Reactivate to monitor their growth over time, for motivation, and for goal setting. All users described Reactivate as an important mobile app. Conclusions: Our study describes the usability of a mobile app used in adolescent obesity management. Adolescents found Reactivate easy to use and their SUMI results indicated that the app scored high on user satisfaction. Usability testing is an important step towards refining the development of the Reactivate app, which can be used in the treatment of obesity. The study on the clinical efficacy of the Reactivate app is currently underway. [JMIR Mhealth Uhealth 2014;2(2):e29]

Health technology assessment (HTA)--the provision to decision makers of information on the value of treatments and tests--has come of age in the last two decades. But it has deep roots in health care, with notable landmarks in (1) the mid eighteenth-century development of empiricism, (2) the twentieth century interest in outcomes and variation in health care, and (3) the pioneering work of Archie Cochrane and others in the 1970s. Three main forces have driven the recent developments of HTA: a combination of concerns about the adoption of unproven technologies, rising costs, and an inexorable rise in consumer expectations. The HTA response, essentially initiatives supporting the provision of reliable synthesised research information on the effects and costs of health technologies, have been well supported in the United Kingdom and internationally. We can be sure that HTA is here to stay.

BACKGROUND: Pericarditis is the inflammation of the pericardium, the membranous sac surrounding the heart. Recurrent pericarditis is the most common complication of acute pericarditis, causing severe and disabling chest pains. Recurrent pericarditis affects one in three patients with acute pericarditis within the first 18 months. Colchicine has been suggested to be beneficial in preventing recurrent pericarditis. OBJECTIVES: To review all randomised controlled trials (RCTs) that assess the effects of colchicine alone or combined, compared to any other intervention to prevent further recurrences of pericarditis, in people with acute or recurrent pericarditis. SEARCH METHODS: We searched the following bibliographic databases on 4 August 2014: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of 12, 2014 on The Cochrane Library), MEDLINE (OVID, 1946 to July week 4, 2014), EMBASE (OVID, 1947 to 2014 week 31), and the Conference Proceedings Citation Index - Science on Web of Science (Thomson Reuters) 1990 to 1 Aug 2014. We did not apply any language or time restrictions. SELECTION CRITERIA: RCTs of people with acute or recurrent pericarditis who are receiving colchicine compared to any other treatment, in order to prevent recurrences. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The first primary outcome was the time to recurrence, measured by calculating the hazard ratios (HRs). The second primary outcome was the adverse effects of colchicine. Secondary outcomes were the rate of recurrences at 6, 12 and 18 months, and symptom relief. MAIN RESULTS: We included four RCTs, involving 564 participants in this review. We compared the effects of colchicine in addition to a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen, aspirin or indomethacin to the effects of the NSAID alone. Two comparable trials studied the effects of colchicine in 204 participants with recurrent pericarditis and two trials studied 360 people with acute pericarditis. All trials had a moderate quality for the primary outcomes. We identified two on-going trials; one of these trials examines acute pericarditis and the other assesses recurrent pericarditis.There was moderate quality evidence that colchicine reduces episodes of pericarditis in people with recurrent pericarditis over 18 months follow-up (HR 0.37; 95% confidence interval (CI) 0.24 to 0.58). It is expected that at 18 months, the number needed to treat (NNT) is 4. In people with acute pericarditis, there was moderate quality evidence that colchicine reduces recurrence (HR 0.40; 95% CI 0.27 to 0.61) at 18 months follow-up. Colchicine led to a greater chance of symptom relief at 72 hours (risk ratio (RR) 1.4; 95% CI 1.26 to 1.56; low quality evidence). Adverse effects were mainly gastrointestinal and included abdominal pain and diarrhoea. The pooled RR for adverse events was 1.26 (95% CI 0.75 to 2.12). While the number of people experiencing adverse effects was higher in the colchicine than the control groups (9% versus 7%), the quality of evidence was low owing to imprecision, and there was no statistically significant difference between the treatment groups (P = 0.42). There was moderate quality evidence that treatment with colchicine led to more people stopping treatment due to adverse events (RR 1.87; 95% CI 1.02 to 3.41). AUTHORS' CONCLUSIONS: Colchicine, as adjunctive therapy to NSAIDs, is effective in reducing the number of pericarditis recurrences in patients with recurrent pericarditis or acute pericarditis. However, evidence is based on a limited number of small trials. Patients with multiple resistant recurrences were not represented in any published or on-going trials, and it is these patients that are in the most need for treatment.

Background: There are few evidence-based mobile health solutions for treating adolescent obesity. The primary aim of this parallel non-inferiority trial is to assess the effectiveness of an experimental smartphone application in reducing obesity at 12 months, compared to the Temple Street W82GO Healthy Lifestyles intervention.Methods/design: The primary outcome measure is change in body mass index standardised deviation score at 12 months. The secondary aim is to compare the effect of treatment on secondary outcomes, including waist circumference, insulin sensitivity, quality of life, physical activity and psychosocial health. Adolescents with a body mass index at or above the 98th percentile (12 to 17 years) will be recruited from the Obesity clinic at Temple Street Children's University Hospital in Dublin, Ireland. W82GO is a family-based lifestyle change intervention delivered in two phases over 12 months. In the current study, participants will be randomised for phase two of treatment to either usual care or care delivered via smartphone application. One hundred and thirty-four participants will be randomised between the two study arms. An intention-to-treat analysis will be used to compare treatment differences between the groups at 12 months.Discussion: The results of this study will be disseminated via open access publication and will provide important information for clinicians, patients and policy makers regarding the use of mobile health interventions in the management of adolescent obesity.Trial registration: Clinicaltrials.gov NCT01804855. © 2014 O'Malley et al.; licensee BioMed Central Ltd.

Background Heparin intermittent flushing is a standard practice in the maintenance of patency in central venous catheters. However, we could find no systematic review examining its effectiveness and safety. Objectives To assess the effectiveness of intermittent flushing with heparin versus 0.9% sodium chloride (normal saline) solution in adults with central venous catheters in terms of prevention of occlusion and overall benefits versus harms. Search methods The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched December 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11). Searches were also carried out in MEDLINE, EMBASE, CINAHL and clinical trials databases (December 2013). Selection criteria Randomised controlled trials (RCTs) in adults 18 years of age and older with a central venous catheter (CVC) in which intermittent flushing with heparin (any dose with or without other drugs) was compared with 0.9% normal saline were included. No restriction on language was applied. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted data. Trial authors were contacted to retrieve additional information, when necessary. Main results Six eligible studies with a total of 1433 participants were included. The heparin concentrations used in these studies were very different (10-5000 IU/mL), and follow-up varied from 20 days to 180 days. The overall risk of bias in the studies was low. The quality of the evidence ranged from very low to moderate for the main outcomes (occlusion of CVC, duration of catheter patency, CVC-related sepsis, mortality and haemorrhage at any site). Combined findings from three trials in which the unit of analysis was the catheter suggest that heparin was associated with reduced CVC occlusion rates (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.29 to 0.94). However, no clear evidence of a similar effect was found when the results of two studies in which the unit of analysis was the participant were combined (RR 0.21, 95% CI 0.03 to 1.70), nor when findings were derived from one study, which considered total line accesses (RR 1.08, 95% CI 0.84 to 1.40). Furthermore, results for other estimated effects were found to be imprecise and compatible with benefit and harm: catheter duration in days (mean difference (MD) 0.41, 95% CI -1.29 to 2.12), CVC-related thrombosis (RR 1.22, 95% CI 0.74 to 1.99), CVC-related sepsis (RR 1.02, 95% CI 0.34 to 3.03), mortality (RR 0.77, 95% CI 0.45 to 1.32) and haemorrhage at any site (RR 1.37, 95% CI 0.49 to 3.85). Authors' conclusions We found no conclusive evidence of important differences when heparin intermittent flushing was compared with 0.9% normal saline flushing for central venous catheter maintenance in terms of efficacy or safety. As heparin is more expensive than normal saline, our findings challenge its continued use in CVC flushing outside the context of clinical trials.

Objective: To review systematically inpatient compared to outpatient care for the treatment of anorexia nervosa and other eating disorders. Method: Search of electronic databases, references and contact with experts to identify randomized controlled trials (RCTs), case–control studies and case series. Study quality was assessed and data extracted by two independent researchers. Results: Two RCTs and seven case series were identified. Unpublished 5-year follow-up data from one RCT showed a (non-statistically significant) improvement in percentage well in the outpatient compared to the inpatient group, but no difference in mortality. Case series were difficult to interpret because of the inherent biases – follow-up varied from 1.5 to 11.7 years and showed wide variations in outcome. Discussion: There is no evidence that inpatient treatment is more (or less) effective than outpatient treatment for people with anorexia nervosa in the long term. Short-term emergency inpatient treatment of the consequences of eating disorders may still be necessary. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association.

[Graphic][1] Pericarditis is inflammation and swelling of the pericardium, the fluid-filled sac surrounding the heart, and causes chest pain. Most acute pericarditis is either idiopathic or follows a viral infection. Acute pericarditis is not usually life threatening and is normally treated medically on an outpatient basis with non-steroidal anti-inflammatory drugs (NSAIDs), and steroids in severe cases or where NSAIDs are contraindicated.1 Recurrence is the most common serious complication and is characterised by the return of severe pericardial pain after recovery from acute pericarditis. Colchicine is a drug with anti-inflammatory properties used for centuries to treat gout. It has also been used for many years by some as adjunct medication in the treatment of pericarditis.1 However, it was not until the beginning of this millennium that the effectiveness of colchicine in pericarditis was evaluated in a randomised controlled trial (RCT).1 This was followed by more RCTs, making it desirable to collate and summarise the available evidence in a systematic review. A Cochrane systematic review2 was therefore conducted to review colchicine's effect on preventing recurrences of pericarditis (table 1). Four trials were included.1 ,3–5 Two trials1 ,5 assessed 360 individuals with new onset of acute pericarditis and the other two trials3 , … [1]: /embed/inline-graphic-1.gif

Background Oxygen (O-2) is widely used in people with acute myocardial infarction (AMI). Previous systematic reviews concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischaemia or infarct size. Our first Cochrane review in 2010 also concluded there was insufficient evidence to know whether oxygen should be used. Since 2010, the lack of evidence to support this widely used intervention has attracted considerable attention, prompting further trials of oxygen therapy in myocardial infarction patients. It is thus important to update this Cochrane review. Objectives To assess the effects of routine use of inhaled oxygen for acute myocardial infarction (AMI). Search methods We searched the following bibliographic databases on 6 June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO) and Web of Science (Thomson Reuters). LILACS (Latin American and Caribbean Health Sciences Literature) was last searched in September 2016. We also contacted experts to identify eligible studies. We applied no language restrictions. Selection criteria Randomised controlled trials in people with suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or non-STEMI) within 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air, regardless of co-therapies provided to participants in both arms of the trial. Data collection and analysis Two authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. We assessed the quality of studies and the risk of bias according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was death. The measure of effect used was the risk ratio (RR) with a 95% confidence interval (CI). We used the GRADE approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro) to import data from Review Manager 5 and create 'Summary of findings' tables. Main results The updated search yielded one new trial, for a total of five included studies involving 1173 participants, 32 of whom died. The pooled risk ratio (RR) of all-cause mortality in the intention-to-treat analysis was 0.99 (95% CI 0.50 to 1.95; 4 studies, N = 1123; I-2 = 46%; quality of evidence: very low) and 1.02 (95% CI 0.52 to 1.98; 4 studies, N = 871; I-2 = 49%; quality of evidence: very low) when only analysing participants with confirmed AMI. One trial measured pain directly, and two others measured it by opiate usage. The trial showed no effect, with a pooled RR of 0.97 for the use of opiates (95% CI 0.78 to 1.20; 2 studies, N = 250). The result on mortality and pain are inconclusive. There is no clear effect for oxygen on infarct size (the evidence is inconsistent and low quality). Authors' conclusions There is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high quality randomised controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI.

Background Etanercept is a soluble tumour necrosis factor alpha-receptor disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Objectives The purpose of this review was to update the previous Cochrane systematic review published in 2003 assessing the benefits and harms of etanercept for the treatment of RA. In addition, we also evaluated the benefits and harms of etanercept plus DMARD compared with DMARD monotherapy in those people with RA who are partial responders to methotrexate (MTX) or any other traditional DMARD. Search methods Five electronic databases were searched from 1966 to February 2003 with no language restriction. The search was updated to January 2012. Attempts were made to identify other studies by contact with experts, searching reference lists and searching trial registers. Selection criteria All controlled trials (minimum 24 weeks' duration) comparing four possible combinations: 1) etanercept (10 mg or 25 mg twice weekly) plus a traditional DMARD (either MTX or sulphasalazine) versus a DMARD, 2) etanercept plus DMARD versus etanercept alone, 3) etanercept alone versus a DMARD or 4) etanercept versus placebo. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the trials. Main results Three trials were included in the original version of the review. An additional six trials, giving a total of 2842 participants, were added to the 2012 update of the review. The trials were generally of moderate to low risk of bias, the majority funded by pharmaceutical companies. Follow-up ranged from six months to 36 months. Benefit At six to 36 months the American College of Rheumatology (ACR) 50 response rate was statistically significantly improved with etanercept plus DMARD treatment when compared with a DMARD in those people who had an inadequate response to any traditional DMARD (risk ratio (RR) 2.0; 95% confidence interval (CI) 1.3 to 2.9, absolute treatment benefit (ATB) 38%; 95% CI 13% to 59%) and in those people who were partial responders to MTX (RR 11.7; 95% CI 1.7 to 82.5, ATB 36%). Similar results were observed when pooling data from all participants (responders or not) (ACR 50 response rates at 24 months: RR 1.9; 95% CI 1.3 to 2.8, ATB 29%; 36 months: RR 1.6; 95% CI 1.3 to 1.9, ATB 24%). Statistically significant improvement in physical function and a higher proportion of disease remission were observed in combination-treated participants compared with DMARDs alone ((mean difference (MD) -0.36; 95% CI -0.43 to -0.28 in a 0-3 scale) and (RR 1.92; 95% CI 1.60 to 2.31), respectively) in those people who had an inadequate response to any traditional DMARD. All changes in radiographic scores were statistically significantly less with combination treatment (etanercept plus DMARD) compared with MTX alone for all participants (responders or not) (Total Sharp Score (TSS) (scale = 0 to 448): MD -2.2, 95% CI -3.0 to -1.4; Erosion Score (ES) (scale = 0 to 280): MD -1.6; 95% CI -2.4 to -0.9; Joint Space Narrowing Score (JSNS) (scale = 0 to 168): MD -0.7; 95% CI -1.1 to -0.2), and with combination treatment compared with etanercept alone (TSS: MD -1.1; 95% CI -1.8 to -0.5; ES: MD -0.7; 95% CI -1.1 to -0.2; JSNS: MD -0.5, 95% CI -0.7 to -0.2). The estimate of irreversible physical disability over 10 years given the radiographic findings was 0.45 out of 3.0. When etanercept monotherapy was compared with DMARD monotherapy, there was generally no evidence of a difference in ACR50 response rates when etanercept 10 mg or 25 mg was used; at six months etanercept 25 mg was significantly more likely to achieve ACR50 than DMARD monotherapy but this difference was not found at 12, 24 or 36 months. TSS and ES radiographic scores were statistically significantly improved with etanercept 25 mg monotherapy compared with DMARD (TSS: MD -0.7; 95% CI -1.4 to 0.1; ES: MD -0.7; 95% CI -1.0 to -0.3) but there was no evidence of a statistically significant difference between etanercept 10 mg monotherapy and MTX. Harms There was no evidence of statistically significant differences in infections or serious infections between etanercept plus DMARD and DMARD alone at any point in time. Infection rates were higher in people receiving etanercept monotherapy compared with DMARD; however, there were no differences regarding serious infections. For those participants who had an inadequate response to DMARDs, the rate of total withdrawals was lower for the etanercept plus DMARD group compared with DMARD alone (RR 0.53; 95% CI 0.36 to 0.77, ATB 18%). No other statistically significant differences were observed in any of the assessed comparisons. Authors' conclusions Etanercept 25 mg administered subcutaneously twice weekly together with MTX was more efficacious than either etanercept or MTX monotherapy for ACR50 and it slowed joint radiographic progression after up to three years of treatment for all participants (responders or not). There was no evidence of a difference in the rates of infections between groups.

Health care has always sought to improve the health of patients, but our interventions do not always do more good than harm. Sometimes ineffective or harmful interventions are used and effective interventions are not used. A key problem has been that decisions are too often based on inadequate evidence or that sound evidence is overlooked. Basing decisions on evidence involves three steps: finding evidence relating to the decision, evaluating it, and acting on it. Evaluating evidence in turn involves assessing its validity, understanding the findings and their implications, and understanding the relevance of the results in the context of local decision‐making. Developing evidence‐based health care is a collective enterprise which, while not easy, is something to which everyone in the health service can contribute.

Evidence in support of products being assessed by the National Institute for Clinical Excellence can be presented in various ways to make products seem more attractive than they really are During health technology appraisals the National Institute for Clinical Excellence (NICE) invites sponsors of the technology to make a submission in support of their product. These submissions can be of variable quality. We examine some of the more dubious techniques that can be used by sponsoring organisations to make their products seem attractive to those making reimbursement decisions. Although the following “advice” is based on real examples of submissions to NICE, it should be remembered that similar biases can be found in academic, peer reviewed publications and that such practices are not the preserve of industry. ### Generating the evidence

The purpose of public and community health is to improve the health of populations or groups rather than concentrating on individuals. This book examines the ethical issues associated with public and community health. The contributors analyse the major ethical issues in public health - prioritisation, public participation, health promotion and screening - all of which reflect current practice in the UK. They examine what health services should be available, who should have access to which health services, what are the best strategies for preventing disease, how can professional and public views be reconciled and when can an individual's health needs override the choice of a community. The contributors apply up-to-date ethical theory to practical examples in public health practice to provide a comprehensive and accessible introduction to the key issues in public health ethics.

It is widely believed that brain stem dysfunction and cranial nerve palsies in patients with rheumatoid arthritis (RA) are common and related to the vertical translocation of the odontoid process. In our database of 235 patients with seropositive RA and craniocervical junction involvement, we have found a very low incidence of such problems. Long tract signs were common, but loss of proprioception (joint position sensation) as the sole neurologic deficit was rare. Nystagmus was found to be associated with the tonsillar herniation of a Chiari 1 malformation and loss of joint position sensation with severe compression of the posterior aspect of the spinal cord at the craniocervical junction. The implications for posterior occipitocervical fusion, particularly by sublaminar wiring, are discussed.

Background Informed consent is a requirement for all research. It is not, however, clear how much information is sufficient to make an informed decision about participation in research. Information on an online questionnaire about childhood development was provided through an unfolding electronic participant sheet in three levels of information. Methods 552 participants, who completed the web-based survey, accessed and spent time reading the participant information sheet (PIS) between July 2008 and November 2009. The information behaviour of the participants was investigated. The first level contained less information than might be found on a standard PIS, the second level corresponded to a standard PIS, and the third contained more information than on a standard PIS. The actual time spent on reading the information provided in three incremental levels and the participants9 evaluation of the information were calculated. Results 77% of the participants chose to access the first level of information, whereas 12% accessed the first two levels, 6% accessed all three levels of information and 23% participated without accessing information. The most accessed levels of information were those that corresponded to the average reading times. Conclusion The brief information provided in the first level was sufficient for participants to make informed decisions, while a sizeable minority of the participants chose not to access any information at all. This study adds to the debate about how much information is required to make a decision about participation in research and the results may help inform the future development of information sheets by providing data on participants9 actual needs when deciding about questionnaire surveys.

Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe.We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM.One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering.All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.

Background\ud TNF-alpha inhibitors have been shown to reduce the risk of joint damage and improve physical function and quality of life in people with rheumatoid arthritis (RA). This is the first Cochrane review of certolizumab pegol, a new TNF-alpha inhibitor.\ud \ud Objectives\ud To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs).\ud \ud Search methods\ud We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to November 2009), EMBASE (1966 to November 2009), Scopus (January 2004 to November 2009), TOXLINE (until November 2009), Web of Knowledge (until November 2009); websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA) (until November 2009), and reference lists of articles.\ud \ud Selection criteria\ud Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult RA patients with active rheumatoid arthritis despite current or prior treatment with conventional DMARDs, such as methotrexate (MTX).\ud \ud Data collection and analysis\ud Two authors independently assessed search results, trial quality and extracted data.\ud \ud Main results\ud Five trials were included. We included in the analysis 2394 people for effectiveness and 2094 people for safety. The duration of follow-up was from 12 to 52 weeks, and the range of doses of certolizumab pegol were from 50 to 400 mg subcutaneously (sc). In three trials the control was placebo plus methotrexate (MTX) and in two trials it was just placebo. Significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol: American College of Rheumatology (ACR) 50% improvement: risk ratio (RR) 6.01 (95% CI 3.84 to 9.40) with an absolute benefit of 29% (95% CI 25% to 34%), number needed to treat to benefit (NNTB) of 4 (3 to 5) and the Health Assessment Questionnaire (HAQ) mean difference (MD) - 0.39 (95% CI -0.45 to -0.32) (scale 0 to 3). At 52 weeks the results were quite similar: ACR 50% improvement RR 5.27 (95% CI 3.19 to 8.71), HAQ mean difference (MD) - 0.42 (95% CI -0.52 to -0.32). Serious adverse events were more frequent for certolizumab pegol 200 mg, Peto OR 2.02 (95% CI 1.24 to 3.30). The most common adverse events with certolizumab pegol 200 mg were: upper respiratory tract infections, Peto OR 2.21 (95% CI 1.15 to 4.25); hypertension, Peto OR 2.81 (95% CI 1.38 to 5.75); and nasopharyngitis, Peto OR 2.71 (95% CI 1.30 to 5.66).\ud \ud Authors' conclusions\ud With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.

Following sciatic nerve crush at birth, approximately 70% of motoneurons to the soleus and 60% of motoneurons to the tibialis anterior (TA) and to the extensor digitorum longus (EDL) die. However, following nerve injury at 5 days, there is negligible motoneuron death. We investigated whether the interaction between the nerve and its target during these 5 days is an important factor for the ability of the motoneuron to survive injury. Nerve - muscle interaction was blocked shortly after birth by alpha-bungarotoxin (BTX) and the effect on motoneuron survival after subsequent injury was examined. It was confirmed that sciatic nerve crush at 5 days produced no significant reduction in motoneuron numbers. However, if nerve crush was preceded by paralysis with alpha-bungarotoxin, the number of surviving motoneurons after nerve injury at 5 days was substantially reduced. On the operated side only 43 +/- 6.68% of the motoneurons of the soleus pool survived and even fewer, 14 +/- 5.0%, in the TA and EDL pool. In a control group of animals paralysed with alpha-bungarotoxin at birth but receiving no nerve crush, there was no appreciable reduction in the motoneuron numbers at 28 days in either motor pool. It is concluded that blocking of nerve - muscle interaction by paralysis in early postnatal life reduces the motoneurons' ability to survive nerve injury later in life, and that this effect is more severe for the motoneurons to the TA and EDL than to the soleus.

Objectives: To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. Data sources: Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. Review methods: The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. Results: Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-close strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behavior and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both, MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was £12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was £30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was £13,697/QALY, for BMT versus no drug therapy that the ICER was £26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. Conclusions: Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

Background: A variety of definitions of evidence-based practice (EBP) exist. However, definitions are in themselves insufficient to explain the underlying processes of EBP and to differentiate between an evidence-based process and evidence-based outcome. There is a need for a clear statement of what Evidence-Based Practice (EBP) means, a description of the skills required to practise in an evidence-based manner and a curriculum that outlines the minimum requirements for training health professionals in EBP. This consensus statement is based on current literature and incorporating the experience of delegates attending the 2003 Conference of Evidence-Based Health Care Teachers and Developers ("Signposting the future of EBHC"). Discussion: Evidence-Based Practice has evolved in both scope and definition. Evidence-Based Practice (EBP) requires that decisions about health care are based on the best available, current, valid and relevant evidence. These decisions should be made by those receiving care, informed by the tacit and explicit knowledge of those providing care, within the context of available resources. Health care professionals must be able to gain, assess, apply and integrate new knowledge and have the ability to adapt to changing circumstances throughout their professional life. Curricula to deliver these aptitudes need to be grounded in the five-step model of EBP, and informed by ongoing research. Core assessment tools for each of the steps should continue to be developed, validated, and made freely available. Summary: All health care professionals need to understand the principles of EBP, recognise EBP in action, implement evidence-based policies, and have a critical attitude to their own practice and to evidence. Without these skills, professionals and organisations will find it difficult to provide 'best practice'.