Search

StatementThe authors have withdrawn their manuscript owing to a reporting error that we have identified in the conduct of this updated systematic review.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.

BackgroundWhile it is now apparent clinical sequelae (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 help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.MethodsA living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.ResultsA total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case–control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general 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%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.ConclusionLong COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. 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.PROSPERO registration numberCRD42020211131.

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.

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.

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: Dyspnoea is a common symptom in COPD and can lead to progressive decline in exercise capacity. Non-Invasive Ventilation has been shown to improve symptoms and exercise capacity but is clinically impractical due to logistical constraints. A portable ventilation device (Vitabreath) may overcome these barriers and be a useful adjunct therapy.\ud \ud Aim: To investigate the effect of Vitabreath on exercise capacity in patients with COPD.\ud \ud Methods: Randomised crossover design; 12 participants with COPD (FEV1% 45±15) performed 3 Six-Minute Walk Tests using i) Vitabreath, ii) Threshold Positive Expiratory Pressure (PEP), or iii) no device. Primary outcome: six-minute walk distance (6MWD). Secondary outcomes: changes in heart rate, oxygen saturations (SpO2), dyspnoea, and lower limb (LL) fatigue, and recovery time of each variable.\ud \ud Results: Mean 6MWD was less using Vitabreath compared to no device (p=0.01). Use of Vitabreath resulted in a smaller change in dyspnoea (p=0.008) and LL fatigue scores (p=0.02), and a faster LL recovery time (p=0.01) compared to Threshold PEP. SpO2 recovery time was faster using Vitabreath compared to both Threshold PEP (p=0.008) and no device (p=0.03).\ud \ud Conclusion: The data suggest no benefit in using the Vitabreath in improving exercise capacity.

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.

Background\ud Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% NaCl (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9% NaCl to see if the evidence establishes whether one is better than the other. This work is an update of a review first published in 2014.\ud \ud Objectives\ud To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline (NS) in adults to prevent occlusion.\ud \ud Search methods\ud The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 11 June 2018) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5). Searches were also carried out in MEDLINE, Embase, CINAHL, and clinical trials databases (11 June 2018).\ud \ud Selection criteria\ud We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus NS. We applied no restriction on language.\ud \ud Data collection and analysis\ud Two review authors independently selected trials, assessed quality, and extracted data. We contacted trial authors to retrieve additional information, when necessary.We carried out statistical analysis using ReviewManager 5 and assessed the overall quality of the evidence supporting assessed outcomes using GRADE. We carried out prespecified subgroup analysis.\ud \ud Main results\ud We identified five new studies for this update (six prior studies were included in the original review), bringing the number of eligible studies to 11, with a total of 2392 participants. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Combined results fromthese studies showed fewer occlusions with heparin than with NS (risk ratio (RR) 0.70, 95%confidence interval (CI) 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%) and provided very low-quality evidence. We carried out subgroup analysis by unit of analysis (testing for subgroup differences (P = 0.23; I² = 30.3%). When the unit of analysis was the participant, results show no clear differences in all occlusions between heparin and NS (RR 0.79, 95% CI 0.58 to 1.08; P = 0.15; 1672 participants; seven studies). Subgroup analysis using the catheter as the unit of analysis shows fewer occlusions with heparin use (RR 0.53, 95% CI 0.29 to 0.95; P = 0.03; 1025 catheters; three studies). When the unit of analysis was line access, results show no clear differences in occlusions between heparin and NS (RR 1.08, 95% CI 0.84 to 1.40; 770 line accesses; one study). We found no clear differences in the duration of catheter patency (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; P = 0.11; 1036 participants; 752 catheters; six studies; low-quality evidence). We found no clear evidence of a difference in the following: CVC-related sepsis (RR 0.74, 95% CI 0.03 to 19.54; P = 0.86; 1097 participants; two studies; low-quality evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; P = 0.33; 1100 participants; three studies; low-quality evidence); haemorrhage at any site (RR 1.32, 95% CI 0.57 to 3.07; P = 0.52; 1245 participants; four studies; moderatequality evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; P = 0.31; 443 participants; three studies; low-quality evidence). Themain reasons for downgrading the quality of evidencewere unclear allocation concealment, imprecision, and suspicion of publication bias.\ud \ud Authors’ conclusions\ud Given the very low quality of the evidence, we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS. Low-quality evidence suggests that heparin may have little or no effect on catheter patency. Although we found no evidence of differences in safety (sepsis, mortality, or haemorrhage), the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia.

Background Funders encourage lay-volunteer inclusion in research but this is not without controversy or resistance, given concerns of role confusion, exploratory methods and limited evidence about what value this brings to research. This overview explores these elements. Methods Eleven databases and gray literature were searched without date or language restrictions for systematic reviews of public involvement in clinical trials design. This systematic overview of patient and public involvement (PPI) included 27 reviews from which areas of good and bad practice were identified. PPI strengths, weaknesses, opportunities and threats were explored through use of meta-narrative analysis. Results Inclusion criteria was met by 27 reviews. Confidence in the findings was assessed using Cerqual, Nice-H, CASP for qualitative research and CASP systematic reviews. Quality ranged from high (n=7), medium (n=14) to low (n=6) in the reviews. Four reviews report the risk of bias. Public involvement roles were primarily in agenda setting, steering committees, ethical review, protocol development, and piloting. Research summaries, follow-up, and dissemination contained PPI, with lesser involvement in data collection, analysis, or manuscript authoring. Trialists report difficulty in finding, retaining, and reimbursing volunteers. Respectful inclusion, role recognition, mutual flexibility, advance planning and sound methods were reported as facilitating public involvement in research. Public involvement was reported to have increased the quantity and quality of patient relevant priorities and outcomes, enrollment, funding, design, implementation and dissemination. Challenges identified include lack of clarity within common language, roles and research boundaries; while logistical needs include extra time, training and funding, Researchers report struggling to report involvement and avoid tokenism. Conclusions Involving patients and the public in clinical trials design, can be beneficial but requires resources, preparation, training, flexibility and time. Issues to address include reporting deficits in the areas of risk of bias, study quality and conflicts of interests. There is a need for improved dissemination strategies to increase public involvement and health literacy. Improvements in funding, training, and reporting of PPI are needed to facilitate meaningful and effective PPI.

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\ud People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior.\ud \ud Objectives\ud Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL). This library was to be in the form of a database containing learning resources for those who are responsible for encouraging critical thinking about treatment claims, and was to be made available online. We wished to include resources for groups we identified as ‘intermediaries’ of knowledge, i.e. teachers of schoolchildren, undergraduates and graduates, for example those teaching evidence-based medicine, or those communicating treatment claims to the public. In selecting resources, we wished to draw particular attention to those resources that had been formally evaluated, for example, by the creators of the resource or independent research groups.\ud \ud Methods\ud CARL was populated with learning-resources identified from a variety of sources—two previously developed but unmaintained inventories; systematic reviews of learning-interventions; online and database searches; and recommendations by members of the project group and its advisors. The learning-resources in CARL were organised by ‘Key Concepts’ needed to judge the trustworthiness of treatment claims, and were made available online by the James Lind Initiative in Testing Treatments interactive (TTi) English (www.testingtreatments.org/category/learning-resources).TTi English also incorporated the database of Key Concepts and the Claim Evaluation Tools developed through the Informed Healthcare Choices (IHC) project (informedhealthchoices.org).\ud \ud Results\ud We have created a database of resources called CARL, which currently contains over 500 open-access learning-resources in a variety of formats: text, audio, video, webpages, cartoons, and lesson materials. These are aimed primarily at ‘Intermediaries’, that is, ‘teachers’, ‘communicators’, ‘advisors’, ‘researchers’, as well as for independent ‘learners’. The resources included in CARL are currently accessible at www.testingtreatments.org/category/learning-resources\ud \ud Conclusions\ud We hope that ready access to CARL will help to promote the critical thinking about treatment claims, needed to help improve healthcare choices.

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.

ObjectiveTo review the evidence for the efficacy and safety of colchicine in children with pericarditis.DesignSystematic review.Search strategyThe following databases were searched for studies about colchicine in children with pericarditis (June 2015): Cochrane Central, Medline, EMBASE and LILACS.Eligibility criteriaAll observational and experimental studies on humans with any length of follow-up and no limitations on language or publication status were included. The outcomes studied were recurrences of pericarditis and adverse events.Data extractionTwo authors extracted data and assessed quality of included studies using the Cochrane risk of bias tool for non-randomised trials.ResultsTwo case series and nine case reports reported the use of colchicine in a total of 86 children with pericarditis. Five articles including 74 paediatric patients were in favour of colchicine in preventing further pericarditis recurrences. Six studies including 12 patients showed that colchicine did not prevent recurrences of pericarditis.LimitationsNo randomised controlled trials (RCTs) were found.ConclusionsAlthough colchicine is an established treatment for pericarditis in adults, it is not routinely used in children. There is not enough evidence to support or discourage the use of colchicine in children with pericarditis. Further research in the form of large double-blind RCTs is needed to establish the efficacy of colchicine in children with pericarditis.

BACKGROUND: The evidence-based medicine (EBM) approach to clinical practice has been incorporated into medical training around the world. Whilst EBM is a component of the 'foundation years' (FY) programme, it appears to lack a firm foundation in the UK undergraduate curriculum. AIM: To identify whether the teaching of EBM is adequately supported by the guideline 'Tomorrow's Doctors' (TD-2003). METHODS: We mapped TD-2003 against the five steps of EBM and also reviewed the literature for reports concerning the introduction of EBM into undergraduate curricula. RESULTS: Whilst all five steps of EBM can be mapped against TD-2003, the guidance makes no explicit reference to EBM and a coherent framework is lacking. The focus of undergraduate EBM teaching should be on 'using' research evidence (rather than undertaking research). The current emphasis on 'therapy' should be expanded to include the EBM-related issues of 'diagnosis, prognosis and harm'. UK medical schools also need to exploit the NHS investment in 'national electronic libraries'.

Background\ud Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol.\ud \ud Objectives\ud To assess the clinical benefits and harms of certolizumab pegol (CZP) in people 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 (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016.\ud \ud Selection criteria\ud Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX.\ud \ud Data collection and analysis\ud Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author.\ud \ud Main results\ud We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo.\ud \ud The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes:\ud \ud - American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies.\ud \ud - The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function).\ud \ud - Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies.\ud \ud - Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference.\ud \ud -Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies.\ud \ud There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies.\ud \ud We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency.\ud \ud Authors' conclusions\ud The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events.

The search engine is now as essential as the stethoscope What we know about diseases, diagnosis, and effective treatments is growing rapidly. Today health professionals cannot solely rely on what they were first taught if they want to do the best for their patients. It has repeatedly been shown that clinical performance deteriorates over time.1 A commitment to lifelong learning must be integral to ethical professional practice. However, the speed of the increase in knowledge—more than 2000 new research papers are added to Medline each day—represents a challenge.2 The skills needed to find potentially relevant studies quickly and reliably, to separate the wheat from the chaff, and to apply sound research findings to patient care have today become as essential as skills with a stethoscope. The advent of “evidence based medicine” saw an explosion of systematic reviews and guidelines but much less change in the medical curriculum.3 4 Although evidence based guidelines may help clinicians in selected areas, they cannot cover the range of questions or have the timeliness …

Summary Aim To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. Methods We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. Results There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI −1.2–1.4). Conclusion An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.

Traditionally, the management of bleeding trauma patients has included early rapid fluid replacement on scene. However, evidence shows that a delay to definitive treatment (control of bleeding) may be harmful and UK policy advocates minimal delay on scene with intravenous fluids being administered in transit to hospitals. This paper systematically reviews the evidence for administering fluids in pre-hospital trauma patients with no head injury. Randomized controlled trials comparing immediate and delayed fluid replacement were sought using formal search strategies. Study selection, quality assessment and data extraction were performed independently by two reviewers using pre-defined criteria. We found no evidence to suggest that pre-hospital fluid administration is beneficial. There is some evidence that it may be harmful and that patients do comparatively well when fluids are withheld. However, this evidence is not conclusive, particularly for blunt trauma, and is not sufficient to disprove current UK policy, which recommends hypotensive resuscitation. © 2006 Sage Publications.

BACKGROUND: Current recommendations for obtaining blood from neonates advise avoidance of the midline area of the heel and are based on postmortem studies. OBJECTIVE: Because of the potential pain and tissue damage from repeated heel pricking in the same area, to investigate using ultrasonography whether the distance from skin to calcaneus is less at the midline than at the borders. METHODS: One hundred consecutive healthy preterm and 105 consecutive healthy term neonates were studied 48-72 hours after delivery. The skin to perichondrium distance (SPD) was measured on two occasions by ultrasound at the external, midline, and internal areas of the heel. FINDINGS: Mean SPD was 0.2 mm less at the midline than at the other sites. The proportion of measurements or = 33 weeks gestation and term infants with an SPD or = 33 weeks gestation. This means that soft tissue damage and pain from repeated pricking in the same area can be reduced.

This review presents and evaluates the evidence of the effectiveness of laser resurfacing for facial acne scars. Primary studies of all types of design in any language were identified from MEDLINE, EMBASE, the Cochrane database, Science Citation Index and various internet sites. Studies were accepted if they included patients treated by any laser for atrophic or ice-pick acne scars. The quality of the studies was assessed and data extracted by two independent researchers. There were no controlled trials but 14 case series were found which reported the effects of either the carbon dioxide or erbium:YAG laser. All of the studies were of poor quality. The types and severity of scarring were poorly described and there was no standard scale used to measure scar improvement. There was no reliable or validated measure of patient satisfaction; most improvement was based on visual clinical judgement, in many cases without blinded assessment. The inaccurate use of ordinal scales meant that any improvement was impossible to quantify with any validity, although the evidence suggested that laser treatment had some efficacy (a range in individual patients of 25–90% for both the carbon dioxide laser and the erbium:YAG laser). Changes in pigmentation as a side-effect were common (in up to 44% of patients), although lasting only a few weeks. Laser resurfacing technology is increasingly used in clinical practice to treat acne scars. Despite the poor quality evidence, it is plausible that there is some improvement of acne scarring; there is insufficient information, however, for patients to make informed decisions on whether to opt for treatment and there is not enough evidence to compare the two types of laser. There is a particular lack of information about the psychological effects of acne scar improvement. Good quality randomized controlled trials are needed with standardized scarring scales and validated patient outcome measures in order to assess the effectiveness of laser resurfacing in this group of patients.

Background Foot orthoses, which are specially moulded devices fitted into footwear, are one of the treatment options for patellofemoral or anterior knee pain. Objectives To assess the effects of foot orthoses for managing patellofemoral pain in adults. Search strategy We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register (March 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (1950 to March 2010), EMBASE (1980 to 2010 Week 11), CINAHL (1937 to March 2010), trial registers, reference lists and grey literature. No language restriction was applied. Selection criteria We included randomised or quasi-randomised clinical studies that compared foot orthoses with flat insoles or another physical therapy intervention. The primary outcomes were knee pain and knee function. Data collection and analysis Two authors independently selected eligible trials, assessed methodological quality and performed data extraction. We calculated risk ratios and 95% confidence intervals for dichotomous variables, and mean differences with 95% confidence intervals for continuous variables. We pooled data using the fixed-effect model. Main results Two trials with a total of 210 participants were included. Both trials were at some risk of performance bias. One trial had four intervention groups and the other had three. One trial found that foot orthoses when compared with flat insoles (control group) had better results at six weeks in knee pain (participants with global improvement: risk ratio 1.48, 95% confidence interval 1.11 to 1.99), but not at one year follow-up. Participants in the orthoses group reported significantly more minor adverse effects (e.g. rubbing, blistering) compared with the flat insole group (risk ratio 1.87, 95% confidence intervaI 1.21 to 2.91). Both trials in their comparisons of orthoses plus physiotherapy versus physiotherapy alone found no statistically significant differences between the two intervention groups in knee pain or function. Results for knee pain outcomes did not show significant differences between foot orthoses versus physiotherapy. Although participants in the physiotherapy group had consistently better results for the functional index questionnaire, the clinical relevance of these results is uncertain. Authors' conclusions While not robust, the available evidence does not reveal any clear advantage of foot orthoses over simple insoles or physiotherapy for patellofemoral pain. While foot orthoses may help relieve knee pain over the short term, the benefit may be marginal. Patients treated with orthoses are more likely to complain of mild adverse effects and discomfort.

Background: Concern has been expressed over UK epilepsy service standards but the most clinically effective model of care is unknown.Objective: To systematically review the current evidence on specialist epilepsy clinics compared to general neurology clinics and specialist epilepsy nurses compared to usual care.Methods: Medline, Psychlit, Embase, Healthplan, GEARS, BIDS ISI, UKCHHO, international HTA websites, InterTASC databases and The Cochrane Library were searched to September 1999. Any studies comparing specialist epilepsy clinics or nurses to generalist services or usual care, reporting physical health, costs or generic quality-of-life outcomes were included. Two people independently applied inclusion and exclusion criteria and extracted data independently. Randomized controlled trial (RCT) quality was assessed by Jadad score and other studies qualitatively by the likelihood of bias.Results: Findings were one RCT and two other studies on epilepsy clinics and four RCTs and a controlled trial on epilepsy nurses. Data synthesis was inappropriate. Epilepsy clinics showed no evidence of reduced seizure frequency or severity, no quality-of-life information and were more expensive. Epilepsy nurse services showed no evidence of reduced seizure frequency or severity, no effect on quality-of-life but were less expensive.Conclusion: There is insufficient evidence to demonstrate the superiority of any particular care model for producing better health outcomes.

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

OBJECTIVES: This report reviews the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab, agents that inhibit tumour necrosis factor-alpha (TNF-alpha), when used in the treatment of rheumatoid arthritis (RA) in adults. DATA SOURCES: Electronic databases were searched up to February 2005. REVIEW METHODS: Systematic reviews of the literature on effectiveness and cost-effectiveness were undertaken and industry submissions to the National Institute for Health and Clinical Excellence (NICE) were reviewed. Meta-analyses of effectiveness data were also undertaken for each agent. The Birmingham Rheumatoid Arthritis Model (BRAM), a simulation model, was further developed and used to produce an incremental cost-effectiveness analysis. RESULTS: Twenty-nine randomised controlled trials (RCTs), most of high quality, were included. The only head-to-head comparisons were against methotrexate. For patients with short disease duration (

BACKGROUND: Most people have acne at some stage during their life, with about one per cent being left with permanent acne scars. Recent laser techniques are thought to be more effective than chemical peels and dermabrasion. OBJECTIVES: To assess the effects of laser resurfacing for treating facial acne scars. SEARCH STRATEGY: We searched MEDLINE (1966 to April 1999), EMBASE (1980 to April 1999), Science Citation Index (1981 to April 1999), the Cochrane Controlled Trials Register (April 1999), DARE (April 1999), INAHTA (April 1999), NHS HTA Internet site (April 1999). Dermatological Surgery (1995 to March 1999) and the British Journal of Dermatology (1995 to September 1999) were handsearched. We searched the reference lists of relevant articles and contacted experts and commercial laser manufacturers. SELECTION CRITERIA: Randomised controlled trials which compare different laser resurfacing techniques for treating patients with facial acne scars, or compare laser resurfacing with other resurfacing techniques or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies, assessed the quality of studies and extracted data. MAIN RESULTS: No randomised controlled trials where laser treatment was compared to either placebo or a different type of laser were found. Most of the 27 studies uncovered were poor quality case series with small numbers of acne-scarred patients. REVIEWER'S CONCLUSIONS: The lack of good quality evidence does not enable any conclusions to be drawn about the effectiveness of lasers for treating atrophic or ice-pick acne scars. Well designed randomised controlled comparisons of carbon dioxide versus Erbium:YAG laser are urgently needed.

Objectives To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus. Data sources MEDLINE, EMBASE and the Cochrane Library. Citation lists of included studies were scanned and relevant professional and patient websites reviewed. Laboratories and manufacturers were contacted to identify ongoing or unpublished research. Review methods Following scoping searches on thyroid and coeliac autoantibodies, a systematic review of autoantibody tests for diagnosis of coeliac disease was carried out. Studies were included where cohorts of untreated patients with unknown disease status were included, all patients had undergone the reference test (biopsy) and antibody tests, and sensitivity and specificity were reported or calculable. Selected studies were then evaluated against a quality checklist. Summary statistics of diagnostic accuracy, i.e. sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios, were calculated for all studies. A decision analytic model was developed to evaluate the cost utility of screening for coeliac disease at diagnosis of diabetes. Results All antibody tests for diagnosis of coeliac disease showed reasonably good diagnostic test accuracy. Studies reported variable measures of test accuracy, which may be due to aspects of study quality, differences in the tests and their execution in the laboratories, different populations and reference standards. The decision analytic model indicated screening for coeliac disease at diagnosis of diabetes was cost-effective. Sensitivity analyses exploring variations in the cost and disutility of gluten-free diet, the utilities attached to treated and untreated coeliac disease and the decrease in life expectancy associated with treated and untreated coeliac disease did substantially affect the cost-effectiveness of the screening strategies considered. Conclusions In terms of test accuracy in testing for coeliac disease, immunoglobulin A (IgA) anti-endomysium is the most accurate test. If an enzyme-linked immunoassay test was required, which may be more suitable for screening purposes as it can be semi-automated, testing for IgA tissue transglutaminase is likely to be most accurate. The decision analytic model shows that the most accurate tests combined with confirmatory biopsy are the most cost-effective, whilst combinations of tests add little or no further value. There is limited information regarding test accuracy in screening populations with diabetes, and there is some uncertainty over whether the test characteristics would remain the same. Further research is required regarding the role of screening in silent coeliac disease and regarding long-term outcomes and complications of untreated coeliac disease.

Background Coronary artery stents are prosthetic linings inserted into coronary arteries via a catheter to widen the artery and increase blood flow to ischaemic heart muscle. They are used in the treatment of ischaemic heart disease (IHD). IHD is a major cause of morbidity and mortality (123,000 deaths per annum) in the UK and a major cost to the NHS. Clinical effects of IHD include subacute manifestations (stable and unstable angina) and acute manifestations (particularly myocardial infarction [MI]). Treatment includes attention to risk factors, drug therapy, percutaneous invasive interventions (PCIs) (including percutaneous transluminal coronary angioplasty [PTCA] and stents) and coronary artery bypass graft surgery (CABG). In the last decade there has been a steady and significant increase in the rate of PCIs for IHD. In the UK, rates per million population increased from 174 in 1991 to 437 in 1998. Stents are now used in about 70% of PCIs. Data from the rest of Europe suggest there is potential for PCI and stent rates to increase considerably. In the UK there is evidence of under-provision and inequity of access to revascularisation procedures. Objectives The following questions were addressed. 1. What are the effects and effectiveness of elective stent insertion versus PTCA in subacute IHD, particularly stable angina and unstable angina? 2. What are the effects and effectiveness of elective stent insertion versus CABG in subacute IHD, particularly stable angina and unstable angina? 3. What are the effects and effectiveness of elective stent insertion versus PTCA in acute MI (AMI)? 4. What are best estimates of UK cost for elective stent insertion, PTCA and CABG in the circumstances of review questions 1 to 3? 5. What are best estimates of cost-effectiveness and cost-utility for elective stent insertion relative to PTCA or CABG in the circumstances of review questions 1 to 3? Methods A systematic review addressing the objectives was undertaken. Data sources A search was made for RCTs comparing stents (inserted during a PTCA procedure) with PTCA alone or with CABG in any manifestation of IHD. The search strategy covered the period from 1990 to November 1999 and included searches of electronic databases (MEDLINE, EMBASE, BIDS ISI, The Cochrane Library), Internet sites, and hand-searches of cardiology conference abstracts and 1999 issues of cardiology journals. Lead researchers and local clinical experts were contacted. Manufacturers' submissions to the National Institute for Clinical Excellence were searched. The search strategy was expanded to look for relevant economic analyses and information to inform the economic model (including searching MEDLINE, the NHS Economic Evaluation Database and the Database of Abstracts of Reviews of Effectiveness). Searches focused on research that reported costs and quality of life data associated with IHD and interventional cardiology. Study selection For the review of clinical effectiveness, inclusion criteria were: (i) RCT design; (ii) study population comprising adults with IHD in native or graft vessels (including patients with subacute IHD or AMI); (iii) procedure involving elective insertion of coronary artery stents; (iv) elective PTCA (including PTCA with provisional stenting) or CABG as comparator; (v) outcomes defined as one or more of: combined event rate (or event-free survival), death, MI, angina, target vessel revascularisation, CABG, repeat PTCA, angiographic outcomes; (vi) trials that had closed and reported results for all or almost all recruited patients. For the economic evaluation, studies of adults with IHD were included if they were of the following types: studies reporting UK costs; comparative economic evaluation combining both costs and outcomes; economic evaluations reporting costs and outcomes separately for the years 1998 and 1999 (to ensure current practice was included).(ABSTRACT TRUNCATED)

© Queen's Printer and Controller of HMSO 2003HTA reports may be freef "×b Y‰ýaeT€s®: | I¾V>c% ;i¥‹|¶¼eU| Þeio° aÂ9a¾¦0¹A[ ayâ?;ðueiA Ks 7 ”EIAoI ýU I²V;I—v Cj“a“s;|¹ PD8 W:/,Ý oE‚a‹½h½+beO7Ÿ\IQ¥Ei8“ƒbh1aTAEUšV©£°:Tk§•C ­-S ×a G[ogg `Ž%AE —Š•AY‡—²¯iOU3 ¢­‡³' a‘AXAu ´eii? D½ EµO¹e²OyaAN\“’‚

Objective To evaluate the effectiveness of uterine-sparing interventions for women with symptomatic uterine fibroids who wish to preserve their uterus. Design Systematic review and indirect comparison meta-analysis. Methods MEDLINE, EMBASE, CENTRAL, conference proceedings, trial registers and reference lists were searched up to October 2013 for randomized controlled trials. Main outcome measures Outcome measures were patient satisfaction, re-intervention and complications rates, reproductive outcomes, and hospitalization and recovery times. Results Five trials, involving 436 women were included; two compared uterine artery embolization with myomectomy and three compared uterine artery embolization with laparoscopic uterine artery occlusion. Indirect treatment comparison showed that myomectomy and uterine artery embolization resulted in higher rates of patient satisfaction (odds ratio 2.56, 95% credible interval 0.56-11.75 and 2.7, 95% credible interval 1.1-7.14, respectively) and lower rates of clinical failure (odds ratio 0.29, 95% credible interval 0.06-1.46 and 0.37, 95% credible interval 0.13-0.93, respectively) than laparoscopic uterine artery occlusion. Myomectomy resulted in lower re-intervention rate than uterine artery embolization (odds ratio 0.08, 95% credible interval 0.02-0.27) and laparoscopic uterine artery occlusion (odds ratio 0.08, 95% credible interval 0.01-0.37) even though the latter techniques had an advantage over myomectomy because of shorter hospitalization and quicker recovery. There was no evidence of difference between the three techniques in ovarian failure and complications rates. The evidence for reproductive outcomes is poor. Conclusion Our study's results suggest that laparoscopic uterine artery occlusion is less effective than uterine artery embolization and myomectomy in treatment of symptomatic fibroids. The choice between uterine artery embolization and myomectomy should be based on individuals' expectations and fully informed discussion. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

A letter to the editor in response to the article "The rationalization of unethical research: revisionist accounts of the Tuskegee Syphilis Study and the New Zealand 'Unfortunate Experiment'" by C. Paul and B. Brookes which was published in the 2015 issue, 105 (10), is presented.