123,966 research outputs found
Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews
Version 3. Overview stabilised in line with the PaPaS Review Group's policy to assess overviews for updating every five years.Differences between protocol and review:
In this updated overview, we made a number of changes compared with the protocol (O'Connell 2011) and the original version of the overview (O'Connell 2013):
• Background: this section has been updated in the current version of the overview to include recent information on CRPS diagnosis, pathophysiology and incidence.
• Searches: in the current version of this overview, we searched Epistemonikos but did not search the Database of Abstracts of Reviews of Effects (DARE), as it is no longer updated.
• Outcomes: in the current version of this overview, we grouped outcomes into post‐intervention, short‐term, medium‐term and long‐term follow‐up periods, reporting only a single effect for each period.
• Assessment of methodological quality of included reviews: in the current version of this overview, we used the revised AMSTAR 2 instead of the original AMSTAR tool to assess the methodological quality of both Cochrane and non‐Cochrane reviews.
• Assessment of the certainty of the evidence in included reviews: where reviews did not use GRADE to assess the certainty in evidence, we conducted these assessments ourselves using updated criteria compared with the previous version of this overview and the protocol (for a full description see Assessment of methodological quality of included reviews). We applied these judgements to all outcomes rather than only the primary outcomes, as done in the previous version of this overview.
• Interpretation of effects: in the current version of this overview, we interpreted minimally important between‐group differences for pain intensity using OMERACT 12 recommendations.Background:
Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.
Objectives:
To summarise the evidence from Cochrane and non‐Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.
Methods:
We identified Cochrane reviews and non‐Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria.
Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well‐being, and participants' ratings of satisfaction or improvement with treatment.
Main results:
We included six Cochrane and 13 non‐Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non‐Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non‐Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high‐certainty evidence for any comparison.
There was low‐certainty evidence that bisphosphonates may reduce pain intensity post‐intervention (standardised mean difference (SMD) ‐2.6, 95% confidence interval (CI) −1.8 to −3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate‐certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181).
There was moderate‐certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low‐certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison.
There was low‐certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N‐acetylcysteine, but no effect size was reported.
There was low‐certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported.
For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low‐ and very low‐certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.
Authors' conclusions:
Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high‐certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high‐quality trials are undertaken, formulating an evidence‐based approach to managing CRPS will remain difficult. Current non‐Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.This project was funded by the National Institute for Health Research (NIHR) via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS). Brunel University, UK: Salary for NOC; University of Notre Dame, Australia: Salary for BW; University College London, UK: Salary for LM; Neuroscience Research Australia, Australia: Salary for JM; University of South Australia, Australia: Salary for GLM
Heterogeneity in search strategies among Cochrane acupuncture reviews: Is there room for improvement?
Objective: Given the international focus and rigorous literature searches employed in Cochrane systematic reviews, this study was undertaken to evaluate strategies employed in Cochrane reviews and protocols assessing acupuncture as a primary or secondary intervention.
Methods: The Cochrane Collaboration of systematic reviews was searched in February 2009 for all reviews and protocols including information on acupuncture. Information was abstracted from all retrieved articles on review status, type and number of English and Chinese language databases searched, participation of at least one Chinese speaking author and language restriction. Frequencies were calculated and bivariate analyses were performed stratifying on interventions of interest to assess differences in search strategy techniques, language restrictions and results.
Results: The search retrieved 68 titles, including 48 completed reviews, 17 protocols and three previously withdrawn titles. Acupuncture was the primary intervention of interest in 44/65 (67.7%) of the retrieved reviews and protocols. While all articles searched at least one English language database, only 26/65 (40.0%) articles searched Chinese language databases. Significantly more articles where acupuncture was the primary intervention of interest searched Chinese language databases (53% vs 9%, p<0.01). Inconclusive findings as to the effectiveness of acupuncture were found in 28/48 (58.3%) of all completed reviews; this type of finding was more common in reviews which did not search any Chinese language databases.
Conclusions: It is important for reviews assessing the effectiveness of acupuncture to search Chinese language databases. The Cochrane Collaboration should develop specific criteria for Chinese language search strategies to ensure the continued publication of high-quality reviews
User involvement in a Cochrane systematic review: using structured methods to enhance the clinical relevance, usefulness and usability of a systematic review update
Background: This paper describes the structured methods used to involve patients, carers and health professionals in an update of a Cochrane systematic review relating to physiotherapy after stroke and explores the perceived impact of involvement.Methods: We sought funding and ethical approval for our user involvement. We recruited a stakeholder group comprising stroke survivors, carers, physiotherapists and educators and held three pre-planned meetings during the course of updating a Cochrane systematic review. Within these meetings, we used formal group consensus methods, based on nominal group techniques, to reach consensus decisions on key issues relating to the structure and methods of the review.Results: The stakeholder group comprised 13 people, including stroke survivors, carers and physiotherapists with a range of different experience, and either 12 or 13 participated in each meeting. At meeting 1, there was consensus that methods of categorising interventions that were used in the original Cochrane review were no longer appropriate or clinically relevant (11/13 participants disagreed or strongly disagreed with previous categories) and that international trials (which had not fitted into the original method of categorisation) ought to be included within the review (12/12 participants agreed or strongly agreed these should be included). At meeting 2, the group members reached consensus over 27 clearly defined treatment components, which were to be used to categorise interventions within the review (12/12 agreed or strongly agreed), and at meeting 3, they agreed on the key messages emerging from the completed review. All participants strongly agreed that the views of the group impacted on the review update, that the review benefited from the involvement of the stakeholder group, and that they believed other Cochrane reviews would benefit from the involvement of similar stakeholder groups.Conclusions: We involved a stakeholder group in the update of a Cochrane systematic review, using clearly described structured methods to reach consensus decisions. The involvement of stakeholders impacted substantially on the review, with the inclusion of international studies, and changes to classification of treatments, comparisons and subgroup comparisons explored within the meta-analysis. We argue that the structured approach which we adopted has implications for other systematic reviews.</p
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Woke-ademia with John Cochrane
John H. Cochrane is the Rose-Marie and Jack Anderson Senior Fellow at the Hoover Institution. He is also a research associate of the National Bureau of Economic Research and an adjunct scholar of the CATO Institute.
Before joining Hoover, Cochrane was a Professor of Finance at the University of Chicago’s Booth School of Business, and earlier at its Economics Department. Cochrane earned a bachelor’s degree in physics at MIT and his PhD in economics at the University of California at Berkeley. He was a junior staff economist on the Council of Economic Advisers (1982–83).
Cochrane’s recent publications include the book Asset Pricing and articles on dynamics in stock and bond markets, the volatility of exchange rates, the term structure of interest rates, the returns to venture capital, liquidity premiums in stock prices, the relation between stock prices and business cycles, and option pricing when investors can’t perfectly hedge. His monetary economics publications include articles on the relationship between deficits and inflation, the effects of monetary policy, and the fiscal theory of the price level. He has also written articles on macroeconomics, health insurance, time-series econometrics, financial regulation, and other topics. He was a coauthor of The Squam Lake Report. His Asset Pricing PhD class is available online via Coursera.
Cochrane frequently contributes editorial opinion essays to the Wall Street Journal, Bloomberg.com, and other publications. He maintains the Grumpy Economist blog.Salem Cente
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John Cochrane: COVID-19 Interview
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John H. Cochrane is the Rose-Marie and Jack Anderson Senior Fellow at the Hoover Institution. He is also a research associate of the National Bureau of Economic Research and an adjunct scholar of the CATO Institute.
Before joining Hoover, Cochrane was a Professor of Finance at the University of Chicago’s Booth School of Business, and earlier at its Economics Department. Cochrane earned a bachelor’s degree in physics at MIT and his PhD in economics at the University of California at Berkeley. He was a junior staff economist on the Council of Economic Advisers (1982–83).
Cochrane’s recent publications include the book Asset Pricing and articles on dynamics in stock and bond markets, the volatility of exchange rates, the term structure of interest rates, the returns to venture capital, liquidity premiums in stock prices, the relation between stock prices and business cycles, and option pricing when investors can’t perfectly hedge. His monetary economics publications include articles on the relationship between deficits and inflation, the effects of monetary policy, and the fiscal theory of the price level. He has also written articles on macroeconomics, health insurance, time-series econometrics, financial regulation, and other topics. He was a coauthor of The Squam Lake Report. His Asset Pricing PhD class is available online via Coursera.
Cochrane frequently contributes editorial opinion essays to the Wall Street Journal, Bloomberg.com, and other publications. He maintains the Grumpy Economist blog.
Listen to the Policy@McCombs podcast to learn more about the data shaping public policy and the data that should be. Subscribe to our YouTube Channel to watch video versions of the podcasts.Salem Cente
Electronic cigarettes for smoking cessation.
"This Cochrane Review was published in the Cochrane Database of Systematic Reviews 2020, Issue 10. Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Cochrane Review."BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. OBJECTIVES: To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses. MAIN RESULTS: We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status
Mobile phone text messaging and app‐based interventions for smoking cessation
BACKGROUND:Mobile phone-based smoking cessation support (mCessation) offers the opportunity to provide behavioural support to those who cannot or do not want face-to-face support. In addition, mCessation can be automated and therefore provided affordably even in resource-poor settings. This is an update of a Cochrane Review first published in 2006, and previously updated in 2009 and 2012. OBJECTIVES:To determine whether mobile phone-based smoking cessation interventions increase smoking cessation rates in people who smoke. SEARCH METHODS:For this update, we searched the Cochrane Tobacco Addiction Group's Specialised Register, along with clinicaltrials.gov and the ICTRP. The date of the most recent searches was 29 October 2018. SELECTION CRITERIA:Participants were smokers of any age. Eligible interventions were those testing any type of predominantly mobile phone-based programme (such as text messages (or smartphone app) for smoking cessation. We included randomised controlled trials with smoking cessation outcomes reported at at least six-month follow-up. DATA COLLECTION AND ANALYSIS:We used standard methodological procedures described in the Cochrane Handbook for Systematic Reviews of Interventions. We performed both study eligibility checks and data extraction in duplicate. We performed meta-analyses of the most stringent measures of abstinence at six months' follow-up or longer, using a Mantel-Haenszel random-effects method, pooling studies with similar interventions and similar comparators to calculate risk ratios (RR) and their corresponding 95% confidence intervals (CI). We conducted analyses including all randomised (with dropouts counted as still smoking) and complete cases only. MAIN RESULTS:This review includes 26 studies (33,849 participants). Overall, we judged 13 studies to be at low risk of bias, three at high risk, and the remainder at unclear risk. Settings and recruitment procedures varied across studies, but most studies were conducted in high-income countries. There was moderate-certainty evidence, limited by inconsistency, that automated text messaging interventions were more effective than minimal smoking cessation support (RR 1.54, 95% CI 1.19 to 2.00; I2 = 71%; 13 studies, 14,133 participants). There was also moderate-certainty evidence, limited by imprecision, that text messaging added to other smoking cessation interventions was more effective than the other smoking cessation interventions alone (RR 1.59, 95% CI 1.09 to 2.33; I2 = 0%, 4 studies, 997 participants). Two studies comparing text messaging with other smoking cessation interventions, and three studies comparing high- and low-intensity messaging, did not show significant differences between groups (RR 0.92 95% CI 0.61 to 1.40; I2 = 27%; 2 studies, 2238 participants; and RR 1.00, 95% CI 0.95 to 1.06; I2 = 0%, 3 studies, 12,985 participants, respectively) but confidence intervals were wide in the former comparison. Five studies compared a smoking cessation smartphone app with lower-intensity smoking cessation support (either a lower-intensity app or non-app minimal support). We pooled the evidence and deemed it to be of very low certainty due to inconsistency and serious imprecision. It provided no evidence that smartphone apps improved the likelihood of smoking cessation (RR 1.00, 95% CI 0.66 to 1.52; I2 = 59%; 5 studies, 3079 participants). Other smartphone apps tested differed from the apps included in the analysis, as two used contingency management and one combined text messaging with an app, and so we did not pool them. Using complete case data as opposed to using data from all participants randomised did not substantially alter the findings. AUTHORS' CONCLUSIONS:There is moderate-certainty evidence that automated text message-based smoking cessation interventions result in greater quit rates than minimal smoking cessation support. There is moderate-certainty evidence of the benefit of text messaging interventions in addition to other smoking cessation support in comparison with that smoking cessation support alone. The evidence comparing smartphone apps with less intensive support was of very low certainty, and more randomised controlled trials are needed to test these interventions
Letter from L. E. Cochrane, Youngstown, Ohio, to Stimpson H. Woodward, Wheeling, West Virginia, September 18, 1869
A document from an extensive collection spanning four generations of the Woodward family that operated merchant pig iron companies in West Virginia and Alabama. The collection begins with Stimpson Harvey Woodward (S. H. Woodward), a native of Massachusetts, who moved from Pittsburgh to Wheeling, West Virginia in 1852. He had interests in an iron company as early as 1852 in West Virginia and began Alabama operations in 1869. The family business continued in Alabama until the death of S. H. Woodward's great-grandson in 1965
Geographies and politics of localism: the localism of the United Kingdom's Coalition Government
There has always been a localist element to British politics. But recently, a particular version of localism has been moved to the foreground by the 2011 Localism Act. This paper identifies various uses and meanings of localism, maps their geographical assumptions and effects, and critiques their politics. It does this using the localism of the United Kingdom’s Coalition Government as a case study of localism in practice. The rationalities, mentalities, programmes, and technologies of this localism are established from Ministerial speeches and press releases, along with Parliamentary Acts, Bills, White Papers, Green Papers, and Statements – all published between May 2010 when the Coalition Government was formed, and November 2011 when the Localism Act became law. We argue that localism may be conceptualised as spatial liberalism, is never straightforwardly local, and can be anti-politica
Specific allergen immunotherapy for the treatment of atopic eczema.
BACKGROUND: Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment. OBJECTIVES: To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema. SEARCH METHODS: We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of Science™ (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE. DATA COLLECTION AND ANALYSIS: Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent-reported global assessment of disease severity at the end of treatment'; 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'; and 'Adverse events, such as acute episodes of asthma or anaphylaxis'. SCORing Atopic Dermatitis (SCORAD) is a means of measuring the effect of atopic dermatitis by area (A); intensity (B); and subjective measures (C), such as itch and sleeplessness, which we used.For 'Participant- or parent-reported global assessment of disease severity at the end of treatment', one trial (20 participants) found improvement in 7/9 participants (78%) treated with the SIT compared with 3/11 (27%) treated with the placebo (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.02 to 7.96; P = 0.04). Another study (24 participants) found no difference: global disease severity improved in 8/13 participants (62%) treated with the SIT compared with 9/11 (81%) treated with the placebo (RR 0.75, 95% CI 0.45 to 1.26; P = 0.38). We did not perform meta-analysis because of high heterogeneity between these two studies. The quality of the evidence was low.For 'Participant- or parent-reported specific symptoms of eczema, by subjective measures', two trials (184 participants) did not find that the SIT improved SCORAD part C (mean difference (MD) -0.74, 95% CI -1.98 to 0.50) or sleep disturbance (MD -0.49, 95% CI -1.03 to 0.06) more than placebo. For SCORAD part C itch severity, these two trials (184 participants) did not find that the SIT improved itch (MD -0.24, 95% CI -1.00 to 0.52). One other non-blinded study (60 participants) found that the SIT reduced itch compared with no treatment (MD -4.20, 95% CI -3.69 to -4.71) and reduced the participants' overall symptoms (P < 0.01), but we could not pool these three studies due to high heterogeneity. The quality of the evidence was very low.Seven trials reported systemic adverse reactions: 18/282 participants (6.4%) treated with the SIT had a systemic reaction compared with 15/210 (7.1%) with no treatment (RR 0.78, 95% CI 0.41 to 1.49; the quality of the evidence was moderate). The same seven trials reported local adverse reactions: 90/280 participants (32.1%) treated with the SIT had a local reaction compared with 44/204 (21.6%) in the no treatment group (RR 1.27, 95% CI 0.89 to 1.81). As these had the same study limitations, we deemed the quality of the evidence to also be moderate.Of our secondary outcomes, there was a significant improvement in 'Investigator- or physician-rated global assessment of disease severity at the end of treatment' (six trials, 262 participants; RR 1.48, 95% CI 1.16 to 1.88). None of the studies reported our secondary outcome 'Parent- or participant-rated eczema severity assessed using a published scale', but two studies (n = 184), which have been mentioned above, used SCORAD part C, which we included as our primary outcome 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'.Our findings were generally inconclusive because of the small number of studies. We were unable to determine by subgroup analyses a particular type of allergen or a particular age or level of disease severity where allergen immunotherapy was more successful. We were also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy. AUTHORS' CONCLUSIONS: Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures
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