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All but three reviews were published in English. Two Chinese reviews and one German review were translated into English. The most common reasons for downgrading were no protocol, no list of full-text exclusions or a literature search restricted to the English language. The included reviews identified 106 studies (77 RCTs and 29 observational studies) that included relevant safety data.

Risk of bias assessments were available from the reviews for 63 RCTs, of which 42 used the Cochrane risk of bias tool. Most of these assessments rated at least one domain as high or unclear roche medical most noticeably selection bias from lack of allocation concealment, performance bias due to lack of blinding of participants and detection bias due to lack of blinding of outcome assessors.

Individual study data and quality assessments are in online supplemental appendix 6. Thirteen reviews provided data on this comparison: 1 high54, 2 low42 47 and 10 critically low quality. Key results can be found in table 2 and additional data in online supplemental appendix 6. Meta-analyses of cutaneous adverse events were presented in two reviews.

We were unable to undertake any further subgroup analyses. Results can be found in online supplemental appendix 6. A meta-analysis of two RCTs99 100 was presented in two systematic reviews. One additional RCT, including 95 young children, reported minor adverse events test and measurement know it all as burning with 2 weeks of potent TCS but no Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA data were presented.

No skin thinning was reported with once or twice daily application of potent TCS for 3 weeks in one RCT (94 adults). Skin thinning and effects on growth concern many people with eczema and parents of children with eczema when using TCS.

Adherence to TCS treatment is known to be poor and these findings, particularly around skin thinning, may encourage appropriate use of TCS and therefore improve treatment effectiveness and patient benefit. Conclusions were limited by the iq 85 of the included reviews because safety was frequently reported in less detail than effectiveness, reviews reported on different adverse events and some adverse events were not described in the reviews.

It is not clear whether this is because the trials did not report adverse events in sufficient detail or whether the review authors did not include all the available safety data, perhaps only focusing on a restricted group of adverse events. None of the included systematic reviews presented data on our prespecified subgroup analyses. Furthermore, most of the included reviews were rated low or critically low-quality using AMSTAR 2.

In addition, where the quality of evidence assessments (eg, GRADE) were reported in the reviews, most individual studies included in the reviews indicated a high or unclear risk in at least one domain. Although short-term TCS use reflects appropriate treatment duration for treating an individual flare, it does not reflect the chronic nature of eczema and the need for TCS use over the long-term. The inclusion of Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA reviews that included vascular studies as well as reviews of RCTs also increased the amount of safety data available to report in this overview.

Although this review focused on the safety of TCS as the key issue for patients, treatment decisions are a balance of benefits and harms. For example, although the safety profile of Chinese herbal medicine was better than TCS, in practice this would be considered alongside the relative effectiveness of these treatments.

Likewise, although there was no difference in the safety of once vs twice daily TCS, effectiveness of these regimens is also important to consider. A Cochrane review is underway comparing the effectiveness and safety of different ways of using TCS. We found that the adverse events of greatest concern to patients and clinicians, such as skin thinning, are uncommon with short-term use of TCS.

However, high-quality evidence was limited, particularly for long-term use. Rather than follow-up of perhaps just a few weeks, future RCTs should include lengthier follow-up to enable better safety assessment. However, it should be noted that longer-term prospect observational studies are better placed to explore longer-term safety of TCS and should be designed with years rather than months of follow-up to add useful information to the field.

Perhaps equally as important as duration of follow-up in trials is resolution of adverse events which is often not reported. For adverse events such as biochemical signs of adrenal suppression, Urofollitropin (Fertinex)- Multum is crucial to know if the effect is transient and levels return to normal once the TCS is stopped, particularly as it is not clear how to interpret the clinical relevance of these.

We would also like to thank Chiau Ming Long for translating two of the included reviews published in Chinese, and to Jonathan Batchelor for confirming exclusion of two reviews published in Japanese.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA. Contributors All authors (EA, JRC, MS, MJR, SL, SML, DJCG, Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA, AR, AA, HCW and KST) helped conceive of and design this overview.

DJCG and EA conducted the searches. EA and JRC carried out the eligibility screening, data extraction coke quality assessments. HCW and KST acted as 3rd reviewers to resolve disagreements. EA performed the statistical analysis and JRC is the study guarantor. Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA and JRC collated and interpreted the y johnson with input from all other authors.

EA and JRC completed the initial drafts of the manuscript and all authors (EA, JRC, Losartan, MJR, SL, SML, DJCG, IM, AR, AA, HCW and KST) commented on and approved the final manuscript.

The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding This report presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (grant ref No. Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the department of Health and Social Care.

Competing interests Authors are coapplicants on an NIHR Programme Grants for Applied Research (P-PG-0216-20007) which funded this overview. The aim of the Programme Grant is to develop an intervention to support eczema self-care and the results of this overview will contribute to this intervention. MJR is funded by an NIHR Post-Doctoral Research Fellowship (PDF-2014-07-013).

HCW was an author on four included reviews, and KST was an author on one included review. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed.

Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ Hyaluronic Acid Dermal Filler Injectable Gel with 0.3% Lidocaine (Restylane-L)- FDA all liability and responsibility arising from any reliance placed on the content.

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Comments:

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