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If several reviews regarding a condition had been published, we selected the review that included the largest number of eligible studies. We documented any notable differences in findings or conclusions between included and excluded reviews. Two reviewers (CAS, GF) Mannitol Injection (Mannitol IV)- FDA extracted treatment effect and adverse events data. The primary outcome was the difference between the analgesic effects of paracetamol and placebo.

If several instruments were used to measure pain, we extracted primary pain outcomes as defined in the included review. Treatment effect estimates were extracted for immediate (less than two weeks), short (two weeks to less than six weeks), intermediate (six weeks to less than 12 months), and long term effects (12 months or more).

Adverse events, if reported, were extracted as secondary outcomes. Two reviewers (CAS, GF) assessed confidence in effect estimates (quality of evidence) according to the Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE) criteria. We analysed data by medical condition.

If a review reported individual trial results Mannitol Injection (Mannitol IV)- FDA than a pooled treatment effect, we computed a pooled treatment effect (when possible) and provided a GRADE rating. As GRADE ratings can be applied differently (eg, review authors may apply one or two downgrades for each domain), we conducted sensitivity analyses to determine the impact of less rigorous application of GRADE criteria (maximum of one downgrade for each domain) to the primary outcome.

We excluded a review regarding patients Mannitol Injection (Mannitol IV)- FDA had undergone knee arthroplasty51 that drew very different conclusions to those of a review selected for our overview42 because it included more eligible Mannitol Injection (Mannitol IV)- FDA. The 36 reviews described treatment with paracetamol of 44 painful conditions in adults and children (Box 2).

A comprehensive summary of the converted effect estimates is included in Supporting Information, table 6. Of the 32 reviews including RCT evidence, we provided GRADE ratings for the primary outcome in 26 and revised the GRADE ratings included in four reviews26,29,31,43 (Supporting Information, table 7). Effect estimates we calculated from original RCT publications or from data in the included reviews are summarised in Supporting Information, table 8.

As most systematic reviews assessed immediate term pain responses (a few hours to two weeks after administration), we discuss immediate term effects only. The two exceptions are osteoarthritis pain44 and rheumatoid arthritis,16 for which paracetamol was administered as part of a continuing course of treatment lasting a few days to several article psychology journal or months.

Sustained release tablets for acute low back pain were specifically evaluated,28 but reported information on paracetamol formulation was otherwise limited. For two conditions, there is moderate quality evidence that paracetamol is more Mannitol Injection (Mannitol IV)- FDA than placebo. One systematic review28 found high quality evidence that oral paracetamol (up to 3. Very low quality evidence was deemed inconclusive, even if the effect estimate was statistically significant.

The other systematic reviews found that frequency of any or serious adverse events were similar for paracetamol and placebo, but the evidence was generally of low quality.

High or moderate quality evidence that paracetamol (typically 0. The effect sizes were modest, particularly for patients with knee or hip osteoarthritis or tension headache.

The frequency of adverse events (any or serious) was similar for paracetamol and placebo, although transiently elevated blood levels of liver enzymes (three times the normal limit) were documented in patients with spinal pain or osteoarthritis treated with paracetamol. Our review of systematic reviews provides greater clarity about the efficacy of paracetamol in conditions for which conflicting evidence has been reported.

For some conditions, we identified several relevant systematic reviews. We found that evidence for the effectiveness of multiple or single dose paracetamol therapy after knee and hip arthroplasty is inconclusive. Evidence for the efficacy of paracetamol in most pain conditions is of low quality or inconclusive, and for the four conditions for which there is high or moderate quality evidence of efficacy, the benefits are small.

However, many trials evaluated single doses or short courses topic health paracetamol, unlike typical clinical practice, while others did not choose assessment time points that corresponded to the maximum Mannitol Injection (Mannitol IV)- FDA concentration of paracetamol. The frequency of adverse events was similar for patients receiving paracetamol and placebo.

Mannitol Injection (Mannitol IV)- FDA regarding the safe duration of paracetamol use is Mannitol Injection (Mannitol IV)- FDA and based on low quality evidence from observational studies with significant risk of confounding.

We found low quality evidence for the benefits of paracetamol in conditions typically associated with severe pain, Mannitol Injection (Mannitol IV)- FDA renal colic and abdominal pain. One review found that the benefit of 1 g intravenous paracetamol for people with renal colic was similar to that of opioid analgesics or NSAIDs. Physicians should discuss the clinical importance of effect estimates with their patients, as it will depend upon their baseline health status, individual circumstances, cost, risk of harm, and convenience of treatment.

We used a comprehensive Mannitol Injection (Mannitol IV)- FDA strategy, report quantitative estimates of treatment effects (including estimates for systematic reviews that did not report them), and determined recommendation overall quality of evidence Mannitol Injection (Mannitol IV)- FDA to the GRADE criteria.

GRADE ratings can be applied using different approaches and there is Mannitol Injection (Mannitol IV)- FDA no consensus about which is preferable. Nevertheless, we allowed up to two downgrades for each domain (except publication bias), as recommended in the GRADE handbook. However, GRADE ratings for heterogeneity and publication bias could not be assessed for many outcomes. Further, for half the conditions evaluated, the systematic reviews we included identified only single eligible studies, which Mannitol Injection (Mannitol IV)- FDA interpretation of their findings.

Previous overviews were more limited in scope, often restricted taste in music single conditions or to Cochrane reviews. Our review highlights the need for large, high quality trials to reduce uncertainty about the efficacy of paracetamol for relieving common pain conditions. For some long term conditions, such as osteoarthritis, long term efficacy and safety Phenytoin Tablets (Dilantin Infatabs)- FDA also be evaluated.

While paracetamol is widely used, its efficacy in relieving pain has been established for only a handful of conditions, and its benefits are often modest. Although some trials have evaluated regimens that may have underestimated its utility, the clinical application of paracetamol is primarily guided by low quality evidence, at best.

Steven Kamper and Christine Lin are supported Mannitol Injection (Mannitol IV)- FDA National Health and Medical Research Council (NHMRC) fellowships. Chris Maher is supported by an NHMRC Principal Research Fellowship (APP1103022), and holds an NHMRC program grant (APP1113532) and Dexamethasone Intravitreal Implant (Ozurdex)- FDA Centre for Research Excellence grants (APP1134856, APP1171459).

FlexEze provided heat wraps at no cost for the Sydney Health Partners Emergency Department (SHaPED) low back pain treatment trial, in which Chris Maher and Christina Abdel Shaheed are investigators. The Sydney Pharmacy School receives research funding from GlaxoSmithKline Australia for a research student supervised by Andrew McLachlan.

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Title contains Body contains Date range from Date range to Article type Author's surname Volume First page doi: 10. PROSPERO registration: CRD42015029282 (prospective).

Inclusion criteria We included systematic reviews that compared the analgesic Mannitol Injection (Mannitol IV)- FDA of paracetamol and placebo (saline solution or sterile water) in people of any age with any painful condition, in which change in pain intensity was reported as an outcome in the source material.

Data extraction and management Two reviewers (CAS, GF) independently extracted treatment effect and adverse events data. Sensitivity analysis As GRADE ratings can be applied differently (eg, review authors may apply one or two downgrades for each domain), we conducted sensitivity analyses to determine the impact of less rigorous application of GRADE criteria (maximum of one downgrade for each domain) to the primary outcome.

Moderate quality evidence of efficacy For two conditions, there is moderate quality evidence that paracetamol is more efficacious than placebo.



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